Detection of Genomic Structural Variants from Next-Generation Sequencing Data
Identifieur interne : 000052 ( Pmc/Corpus ); précédent : 000051; suivant : 000053Detection of Genomic Structural Variants from Next-Generation Sequencing Data
Auteurs : Lorenzo Tattini ; Romina D Urizio ; Alberto MagiSource :
- Frontiers in Bioengineering and Biotechnology [ 2296-4185 ] ; 2015.
Abstract
Structural variants are genomic rearrangements larger than 50 bp accounting for around 1% of the variation among human genomes. They impact on phenotypic diversity and play a role in various diseases including neurological/neurocognitive disorders and cancer development and progression. Dissecting structural variants from next-generation sequencing data presents several challenges and a number of approaches have been proposed in the literature. In this mini review, we describe and summarize the latest tools – and their underlying algorithms – designed for the analysis of whole-genome sequencing, whole-exome sequencing, custom captures, and amplicon sequencing data, pointing out the major advantages/drawbacks. We also report a summary of the most recent applications of third-generation sequencing platforms. This assessment provides a guided indication – with particular emphasis on human genetics and copy number variants – for researchers involved in the investigation of these genomic events.
Url:
DOI: 10.3389/fbioe.2015.00092
PubMed: 26161383
PubMed Central: 4479793
Links to Exploration step
PMC:4479793Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Detection of Genomic Structural Variants from Next-Generation Sequencing Data</title><author><name sortKey="Tattini, Lorenzo" sort="Tattini, Lorenzo" uniqKey="Tattini L" first="Lorenzo" last="Tattini">Lorenzo Tattini</name><affiliation><nlm:aff id="aff1"><institution>Department of Neurosciences, Psychology, Pharmacology and Child Health, University of Florence</institution>,<addr-line>Florence</addr-line>,<country>Italy</country></nlm:aff></affiliation></author><author><name sortKey="D Urizio, Romina" sort="D Urizio, Romina" uniqKey="D Urizio R" first="Romina" last="D Urizio">Romina D Urizio</name><affiliation><nlm:aff id="aff2"><institution>Laboratory of Integrative Systems Medicine (LISM), Institute of Informatics and Telematics and Institute of Clinical Physiology, National Research Council</institution>,<addr-line>Pisa</addr-line>,<country>Italy</country></nlm:aff></affiliation></author><author><name sortKey="Magi, Alberto" sort="Magi, Alberto" uniqKey="Magi A" first="Alberto" last="Magi">Alberto Magi</name><affiliation><nlm:aff id="aff3"><institution>Department of Clinical and Experimental Medicine, University of Florence</institution>,<addr-line>Florence</addr-line>,<country>Italy</country></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">26161383</idno><idno type="pmc">4479793</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4479793</idno><idno type="RBID">PMC:4479793</idno><idno type="doi">10.3389/fbioe.2015.00092</idno><date when="2015">2015</date><idno type="wicri:Area/Pmc/Corpus">000052</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000052</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Detection of Genomic Structural Variants from Next-Generation Sequencing Data</title><author><name sortKey="Tattini, Lorenzo" sort="Tattini, Lorenzo" uniqKey="Tattini L" first="Lorenzo" last="Tattini">Lorenzo Tattini</name><affiliation><nlm:aff id="aff1"><institution>Department of Neurosciences, Psychology, Pharmacology and Child Health, University of Florence</institution>,<addr-line>Florence</addr-line>,<country>Italy</country></nlm:aff></affiliation></author><author><name sortKey="D Urizio, Romina" sort="D Urizio, Romina" uniqKey="D Urizio R" first="Romina" last="D Urizio">Romina D Urizio</name><affiliation><nlm:aff id="aff2"><institution>Laboratory of Integrative Systems Medicine (LISM), Institute of Informatics and Telematics and Institute of Clinical Physiology, National Research Council</institution>,<addr-line>Pisa</addr-line>,<country>Italy</country></nlm:aff></affiliation></author><author><name sortKey="Magi, Alberto" sort="Magi, Alberto" uniqKey="Magi A" first="Alberto" last="Magi">Alberto Magi</name><affiliation><nlm:aff id="aff3"><institution>Department of Clinical and Experimental Medicine, University of Florence</institution>,<addr-line>Florence</addr-line>,<country>Italy</country></nlm:aff></affiliation></author></analytic><series><title level="j">Frontiers in Bioengineering and Biotechnology</title><idno type="eISSN">2296-4185</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Structural variants are genomic rearrangements larger than 50 bp accounting for around 1% of the variation among human genomes. They impact on phenotypic diversity and play a role in various diseases including neurological/neurocognitive disorders and cancer development and progression. Dissecting structural variants from next-generation sequencing data presents several challenges and a number of approaches have been proposed in the literature. In this mini review, we describe and summarize the latest tools – and their underlying algorithms – designed for the analysis of whole-genome sequencing, whole-exome sequencing, custom captures, and amplicon sequencing data, pointing out the major advantages/drawbacks. We also report a summary of the most recent applications of third-generation sequencing platforms. This assessment provides a guided indication – with particular emphasis on human genetics and copy number variants – for researchers involved in the investigation of these genomic events.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Abecasis, G R" uniqKey="Abecasis G">G. R. Abecasis</name></author><author><name sortKey="Altshuler, D" uniqKey="Altshuler D">D. Altshuler</name></author><author><name sortKey="Auton, A" uniqKey="Auton A">A. Auton</name></author><author><name sortKey="Brooks, L D" uniqKey="Brooks L">L. D. Brooks</name></author><author><name sortKey="Durbin, R M" uniqKey="Durbin R">R. M. Durbin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Abyzov, A" uniqKey="Abyzov A">A. Abyzov</name></author><author><name sortKey="Urban, A E" uniqKey="Urban A">A. E. Urban</name></author><author><name sortKey="Snyder, M" uniqKey="Snyder M">M. Snyder</name></author><author><name sortKey="Gerstein, M" uniqKey="Gerstein M">M. Gerstein</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Alkan, C" uniqKey="Alkan C">C. Alkan</name></author><author><name sortKey="Coe, B P" uniqKey="Coe B">B. P. Coe</name></author><author><name sortKey="Eichler, E E" uniqKey="Eichler E">E. E. Eichler</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Alkan, C" uniqKey="Alkan C">C. Alkan</name></author><author><name sortKey="Sajjadian, S" uniqKey="Sajjadian S">S. Sajjadian</name></author><author><name sortKey="Eichler, E E" uniqKey="Eichler E">E. E. Eichler</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Alkan, C" uniqKey="Alkan C">C. Alkan</name></author><author><name sortKey="Kidd, J M" uniqKey="Kidd J">J. M. Kidd</name></author><author><name sortKey="Marques Bonet, T" uniqKey="Marques Bonet T">T. Marques-Bonet</name></author><author><name sortKey="Aksay, G" uniqKey="Aksay G">G. Aksay</name></author><author><name sortKey="Antonacci, F" uniqKey="Antonacci F">F. Antonacci</name></author><author><name sortKey="Hormozdiari, F" uniqKey="Hormozdiari F">F. Hormozdiari</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Alkodsi, A" uniqKey="Alkodsi A">A. Alkodsi</name></author><author><name sortKey="Louhimo, R" uniqKey="Louhimo R">R. Louhimo</name></author><author><name sortKey="Hautaniemi, S" uniqKey="Hautaniemi S">S. Hautaniemi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ashton, P M" uniqKey="Ashton P">P. M. Ashton</name></author><author><name sortKey="Nair, S" uniqKey="Nair S">S. Nair</name></author><author><name sortKey="Dallman, T" uniqKey="Dallman T">T. Dallman</name></author><author><name sortKey="Rubino, S" uniqKey="Rubino S">S. Rubino</name></author><author><name sortKey="Rabsch, W" uniqKey="Rabsch W">W. Rabsch</name></author><author><name sortKey="Mwaigwisya, S" uniqKey="Mwaigwisya S">S. Mwaigwisya</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bansal, V" uniqKey="Bansal V">V. Bansal</name></author><author><name sortKey="Dorn, C" uniqKey="Dorn C">C. Dorn</name></author><author><name sortKey="Grunert, M" uniqKey="Grunert M">M. Grunert</name></author><author><name sortKey="Klaassen, S" uniqKey="Klaassen S">S. Klaassen</name></author><author><name sortKey="Hetzer, R" uniqKey="Hetzer R">R. Hetzer</name></author><author><name sortKey="Berger, F" uniqKey="Berger F">F. Berger</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bayley, H" uniqKey="Bayley H">H. Bayley</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Beadling, C" uniqKey="Beadling C">C. Beadling</name></author><author><name sortKey="Neff, T L" uniqKey="Neff T">T. L. Neff</name></author><author><name sortKey="Heinrich, M C" uniqKey="Heinrich M">M. C. Heinrich</name></author><author><name sortKey="Rhodes, K" uniqKey="Rhodes K">K. Rhodes</name></author><author><name sortKey="Thornton, M" uniqKey="Thornton M">M. Thornton</name></author><author><name sortKey="Leamon, J" uniqKey="Leamon J">J. Leamon</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Boeva, V" uniqKey="Boeva V">V. Boeva</name></author><author><name sortKey="Popova, T" uniqKey="Popova T">T. Popova</name></author><author><name sortKey="Lienard, M" uniqKey="Lienard M">M. Lienard</name></author><author><name sortKey="Toffoli, S" uniqKey="Toffoli S">S. Toffoli</name></author><author><name sortKey="Kamal, M" uniqKey="Kamal M">M. Kamal</name></author><author><name sortKey="Le Tourneau, C" uniqKey="Le Tourneau C">C. Le Tourneau</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Campbell, P J" uniqKey="Campbell P">P. J. Campbell</name></author><author><name sortKey="Stephens, P J" uniqKey="Stephens P">P. J. Stephens</name></author><author><name sortKey="Pleasance, E D" uniqKey="Pleasance E">E. D. Pleasance</name></author><author><name sortKey="O Eara, S" uniqKey="O Eara S">S. O’Meara</name></author><author><name sortKey="Li, H" uniqKey="Li H">H. Li</name></author><author><name sortKey="Santarius, T" uniqKey="Santarius T">T. Santarius</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chaisson, M J" uniqKey="Chaisson M">M. J. Chaisson</name></author><author><name sortKey="Tesler, G" uniqKey="Tesler G">G. Tesler</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chaisson, M J P" uniqKey="Chaisson M">M. J. P. Chaisson</name></author><author><name sortKey="Huddleston, J" uniqKey="Huddleston J">J. Huddleston</name></author><author><name sortKey="Dennis, M Y" uniqKey="Dennis M">M. Y. Dennis</name></author><author><name sortKey="Sudmant, P H" uniqKey="Sudmant P">P. H. Sudmant</name></author><author><name sortKey="Malig, M" uniqKey="Malig M">M. Malig</name></author><author><name sortKey="Hormozdiari, F" uniqKey="Hormozdiari F">F. Hormozdiari</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chen, K" uniqKey="Chen K">K. Chen</name></author><author><name sortKey="Wallis, J W" uniqKey="Wallis J">J. W. Wallis</name></author><author><name sortKey="Mclellan, M D" uniqKey="Mclellan M">M. D. McLellan</name></author><author><name sortKey="Larson, D E" uniqKey="Larson D">D. E. Larson</name></author><author><name sortKey="Kalicki, J M" uniqKey="Kalicki J">J. M. Kalicki</name></author><author><name sortKey="Pohl, C S" uniqKey="Pohl C">C. S. Pohl</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chiang, D Y" uniqKey="Chiang D">D. Y. Chiang</name></author><author><name sortKey="Getz, G" uniqKey="Getz G">G. Getz</name></author><author><name sortKey="Jaffe, D B" uniqKey="Jaffe D">D. B. Jaffe</name></author><author><name sortKey="O Elly, M J T" uniqKey="O Elly M">M. J. T. O’Kelly</name></author><author><name sortKey="Zhao, X" uniqKey="Zhao X">X. Zhao</name></author><author><name sortKey="Carter, S L" uniqKey="Carter S">S. L. Carter</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Conrad, D F" uniqKey="Conrad D">D. F. Conrad</name></author><author><name sortKey="Pinto, D" uniqKey="Pinto D">D. Pinto</name></author><author><name sortKey="Redon, R" uniqKey="Redon R">R. Redon</name></author><author><name sortKey="Feuk, L" uniqKey="Feuk L">L. Feuk</name></author><author><name sortKey="Gokcumen, O" uniqKey="Gokcumen O">O. Gokcumen</name></author><author><name sortKey="Zhang, Y" uniqKey="Zhang Y">Y. Zhang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="De Koning, A P J" uniqKey="De Koning A">A. P. J. de Koning</name></author><author><name sortKey="Gu, W" uniqKey="Gu W">W. Gu</name></author><author><name sortKey="Castoe, T A" uniqKey="Castoe T">T. A. Castoe</name></author><author><name sortKey="Batzer, M A" uniqKey="Batzer M">M. A. Batzer</name></author><author><name sortKey="Pollock, D D" uniqKey="Pollock D">D. D. Pollock</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Desai, A N" uniqKey="Desai A">A. N. Desai</name></author><author><name sortKey="Jere, A" uniqKey="Jere A">A. Jere</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Duan, J" uniqKey="Duan J">J. Duan</name></author><author><name sortKey="Zhang, J G" uniqKey="Zhang J">J.-G. Zhang</name></author><author><name sortKey="Deng, H W" uniqKey="Deng H">H.-W. Deng</name></author><author><name sortKey="Wang, Y P" uniqKey="Wang Y">Y.-P. Wang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Earl, D" uniqKey="Earl D">D. Earl</name></author><author><name sortKey="Bradnam, K" uniqKey="Bradnam K">K. Bradnam</name></author><author><name sortKey="St John, J" uniqKey="St John J">J. St John</name></author><author><name sortKey="Darling, A" uniqKey="Darling A">A. Darling</name></author><author><name sortKey="Lin, D" uniqKey="Lin D">D. Lin</name></author><author><name sortKey="Fass, J" uniqKey="Fass J">J. Fass</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fromer, M" uniqKey="Fromer M">M. Fromer</name></author><author><name sortKey="Moran, J L" uniqKey="Moran J">J. L. Moran</name></author><author><name sortKey="Chambert, K" uniqKey="Chambert K">K. Chambert</name></author><author><name sortKey="Banks, E" uniqKey="Banks E">E. Banks</name></author><author><name sortKey="Bergen, S E" uniqKey="Bergen S">S. E. Bergen</name></author><author><name sortKey="Ruderfer, D M" uniqKey="Ruderfer D">D. M. Ruderfer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Girirajan, S" uniqKey="Girirajan S">S. Girirajan</name></author><author><name sortKey="Dennis, M Y" uniqKey="Dennis M">M. Y. Dennis</name></author><author><name sortKey="Baker, C" uniqKey="Baker C">C. Baker</name></author><author><name sortKey="Malig, M" uniqKey="Malig M">M. Malig</name></author><author><name sortKey="Coe, B P" uniqKey="Coe B">B. P. Coe</name></author><author><name sortKey="Campbell, C D" uniqKey="Campbell C">C. D. Campbell</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gnerre, S" uniqKey="Gnerre S">S. Gnerre</name></author><author><name sortKey="Maccallum, I" uniqKey="Maccallum I">I. Maccallum</name></author><author><name sortKey="Przybylski, D" uniqKey="Przybylski D">D. Przybylski</name></author><author><name sortKey="Ribeiro, F J" uniqKey="Ribeiro F">F. J. Ribeiro</name></author><author><name sortKey="Burton, J N" uniqKey="Burton J">J. N. Burton</name></author><author><name sortKey="Walker, B J" uniqKey="Walker B">B. J. Walker</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gusnanto, A" uniqKey="Gusnanto A">A. Gusnanto</name></author><author><name sortKey="Wood, H M" uniqKey="Wood H">H. M. Wood</name></author><author><name sortKey="Pawitan, Y" uniqKey="Pawitan Y">Y. Pawitan</name></author><author><name sortKey="Rabbitts, P" uniqKey="Rabbitts P">P. Rabbitts</name></author><author><name sortKey="Berri, S" uniqKey="Berri S">S. Berri</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hach, F" uniqKey="Hach F">F. Hach</name></author><author><name sortKey="Hormozdiari, F" uniqKey="Hormozdiari F">F. Hormozdiari</name></author><author><name sortKey="Alkan, C" uniqKey="Alkan C">C. Alkan</name></author><author><name sortKey="Hormozdiari, F" uniqKey="Hormozdiari F">F. Hormozdiari</name></author><author><name sortKey="Birol, I" uniqKey="Birol I">I. Birol</name></author><author><name sortKey="Eichler, E E" uniqKey="Eichler E">E. E. Eichler</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hajirasouliha, I" uniqKey="Hajirasouliha I">I. Hajirasouliha</name></author><author><name sortKey="Hormozdiari, F" uniqKey="Hormozdiari F">F. Hormozdiari</name></author><author><name sortKey="Alkan, C" uniqKey="Alkan C">C. Alkan</name></author><author><name sortKey="Kidd, J M" uniqKey="Kidd J">J. M. Kidd</name></author><author><name sortKey="Birol, I" uniqKey="Birol I">I. Birol</name></author><author><name sortKey="Eichler, E E" uniqKey="Eichler E">E. E. Eichler</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Handsaker, R E" uniqKey="Handsaker R">R. E. Handsaker</name></author><author><name sortKey="Korn, J M" uniqKey="Korn J">J. M. Korn</name></author><author><name sortKey="Nemesh, J" uniqKey="Nemesh J">J. Nemesh</name></author><author><name sortKey="Mccarroll, S A" uniqKey="Mccarroll S">S. A. McCarroll</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Harismendy, O" uniqKey="Harismendy O">O. Harismendy</name></author><author><name sortKey="Ng, P C" uniqKey="Ng P">P. C. Ng</name></author><author><name sortKey="Strausberg, R L" uniqKey="Strausberg R">R. L. Strausberg</name></author><author><name sortKey="Wang, X" uniqKey="Wang X">X. Wang</name></author><author><name sortKey="Stockwell, T B" uniqKey="Stockwell T">T. B. Stockwell</name></author><author><name sortKey="Beeson, K Y" uniqKey="Beeson K">K. Y. Beeson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hart, S N" uniqKey="Hart S">S. N. Hart</name></author><author><name sortKey="Sarangi, V" uniqKey="Sarangi V">V. Sarangi</name></author><author><name sortKey="Moore, R" uniqKey="Moore R">R. Moore</name></author><author><name sortKey="Baheti, S" uniqKey="Baheti S">S. Baheti</name></author><author><name sortKey="Bhavsar, J D" uniqKey="Bhavsar J">J. D. Bhavsar</name></author><author><name sortKey="Couch, F J" uniqKey="Couch F">F. J. Couch</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hormozdiari, F" uniqKey="Hormozdiari F">F. Hormozdiari</name></author><author><name sortKey="Alkan, C" uniqKey="Alkan C">C. Alkan</name></author><author><name sortKey="Eichler, E E" uniqKey="Eichler E">E. E. Eichler</name></author><author><name sortKey="Sahinalp, S C" uniqKey="Sahinalp S">S. C. Sahinalp</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hormozdiari, F" uniqKey="Hormozdiari F">F. Hormozdiari</name></author><author><name sortKey="Hajirasouliha, I" uniqKey="Hajirasouliha I">I. Hajirasouliha</name></author><author><name sortKey="Dao, P" uniqKey="Dao P">P. Dao</name></author><author><name sortKey="Hach, F" uniqKey="Hach F">F. Hach</name></author><author><name sortKey="Yorukoglu, D" uniqKey="Yorukoglu D">D. Yorukoglu</name></author><author><name sortKey="Alkan, C" uniqKey="Alkan C">C. Alkan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hormozdiari, F" uniqKey="Hormozdiari F">F. Hormozdiari</name></author><author><name sortKey="Hajirasouliha, I" uniqKey="Hajirasouliha I">I. Hajirasouliha</name></author><author><name sortKey="Mcpherson, A" uniqKey="Mcpherson A">A. McPherson</name></author><author><name sortKey="Eichler, E E" uniqKey="Eichler E">E. E. Eichler</name></author><author><name sortKey="Sahinalp, S C" uniqKey="Sahinalp S">S. C. Sahinalp</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Iafrate, A J" uniqKey="Iafrate A">A. J. Iafrate</name></author><author><name sortKey="Feuk, L" uniqKey="Feuk L">L. Feuk</name></author><author><name sortKey="Rivera, M N" uniqKey="Rivera M">M. N. Rivera</name></author><author><name sortKey="Listewnik, M L" uniqKey="Listewnik M">M. L. Listewnik</name></author><author><name sortKey="Donahoe, P K" uniqKey="Donahoe P">P. K. Donahoe</name></author><author><name sortKey="Qi, Y" uniqKey="Qi Y">Y. Qi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Iqbal, Z" uniqKey="Iqbal Z">Z. Iqbal</name></author><author><name sortKey="Caccamo, M" uniqKey="Caccamo M">M. Caccamo</name></author><author><name sortKey="Turner, I" uniqKey="Turner I">I. Turner</name></author><author><name sortKey="Flicek, P" uniqKey="Flicek P">P. Flicek</name></author><author><name sortKey="Mcvean, G" uniqKey="Mcvean G">G. McVean</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ivakhno, S" uniqKey="Ivakhno S">S. Ivakhno</name></author><author><name sortKey="Royce, T" uniqKey="Royce T">T. Royce</name></author><author><name sortKey="Cox, A J" uniqKey="Cox A">A. J. Cox</name></author><author><name sortKey="Evers, D J" uniqKey="Evers D">D. J. Evers</name></author><author><name sortKey="Cheetham, R K" uniqKey="Cheetham R">R. K. Cheetham</name></author><author><name sortKey="Tavare, S" uniqKey="Tavare S">S. Tavaré</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jain, M" uniqKey="Jain M">M. Jain</name></author><author><name sortKey="Fiddes, I T" uniqKey="Fiddes I">I. T. Fiddes</name></author><author><name sortKey="Miga, K H" uniqKey="Miga K">K. H. Miga</name></author><author><name sortKey="Olsen, H E" uniqKey="Olsen H">H. E. Olsen</name></author><author><name sortKey="Paten, B" uniqKey="Paten B">B. Paten</name></author><author><name sortKey="Akeson, M" uniqKey="Akeson M">M. Akeson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jiang, Y" uniqKey="Jiang Y">Y. Jiang</name></author><author><name sortKey="Oldridge, D A" uniqKey="Oldridge D">D. A. Oldridge</name></author><author><name sortKey="Diskin, S J" uniqKey="Diskin S">S. J. Diskin</name></author><author><name sortKey="Zhang, N R" uniqKey="Zhang N">N. R. Zhang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jiang, Y" uniqKey="Jiang Y">Y. Jiang</name></author><author><name sortKey="Wang, Y" uniqKey="Wang Y">Y. Wang</name></author><author><name sortKey="Brudno, M" uniqKey="Brudno M">M. Brudno</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kadalayil, L" uniqKey="Kadalayil L">L. Kadalayil</name></author><author><name sortKey="Rafiq, S" uniqKey="Rafiq S">S. Rafiq</name></author><author><name sortKey="Rose Zerilli, M J J" uniqKey="Rose Zerilli M">M. J. J. Rose-Zerilli</name></author><author><name sortKey="Pengelly, R J" uniqKey="Pengelly R">R. J. Pengelly</name></author><author><name sortKey="Parker, H" uniqKey="Parker H">H. Parker</name></author><author><name sortKey="Oscier, D" uniqKey="Oscier D">D. Oscier</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Karakoc, E" uniqKey="Karakoc E">E. Karakoc</name></author><author><name sortKey="Alkan, C" uniqKey="Alkan C">C. Alkan</name></author><author><name sortKey="O Oak, B J" uniqKey="O Oak B">B. J. O’Roak</name></author><author><name sortKey="Dennis, M Y" uniqKey="Dennis M">M. Y. Dennis</name></author><author><name sortKey="Vives, L" uniqKey="Vives L">L. Vives</name></author><author><name sortKey="Mark, K" uniqKey="Mark K">K. Mark</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Keane, T M" uniqKey="Keane T">T. M. Keane</name></author><author><name sortKey="Wong, K" uniqKey="Wong K">K. Wong</name></author><author><name sortKey="Adams, D J" uniqKey="Adams D">D. J. Adams</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kelley, D R" uniqKey="Kelley D">D. R. Kelley</name></author><author><name sortKey="Schatz, M C" uniqKey="Schatz M">M. C. Schatz</name></author><author><name sortKey="Salzberg, S L" uniqKey="Salzberg S">S. L. Salzberg</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kielbasa, S M" uniqKey="Kielbasa S">S. M. Kiełbasa</name></author><author><name sortKey="Wan, R" uniqKey="Wan R">R. Wan</name></author><author><name sortKey="Sato, K" uniqKey="Sato K">K. Sato</name></author><author><name sortKey="Horton, P" uniqKey="Horton P">P. Horton</name></author><author><name sortKey="Frith, M C" uniqKey="Frith M">M. C. Frith</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kim, K E" uniqKey="Kim K">K. E. Kim</name></author><author><name sortKey="Peluso, P" uniqKey="Peluso P">P. Peluso</name></author><author><name sortKey="Babayan, P" uniqKey="Babayan P">P. Babayan</name></author><author><name sortKey="Yeadon, P J" uniqKey="Yeadon P">P. J. Yeadon</name></author><author><name sortKey="Yu, C" uniqKey="Yu C">C. Yu</name></author><author><name sortKey="Fisher, W W" uniqKey="Fisher W">W. W. Fisher</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kim, T M" uniqKey="Kim T">T.-M. Kim</name></author><author><name sortKey="Luquette, L J" uniqKey="Luquette L">L. J. Luquette</name></author><author><name sortKey="Xi, R" uniqKey="Xi R">R. Xi</name></author><author><name sortKey="Park, P J" uniqKey="Park P">P. J. Park</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Klambauer, G" uniqKey="Klambauer G">G. Klambauer</name></author><author><name sortKey="Schwarzbauer, K" uniqKey="Schwarzbauer K">K. Schwarzbauer</name></author><author><name sortKey="Mayr, A" uniqKey="Mayr A">A. Mayr</name></author><author><name sortKey="Clevert, D A" uniqKey="Clevert D">D.-A. Clevert</name></author><author><name sortKey="Mitterecker, A" uniqKey="Mitterecker A">A. Mitterecker</name></author><author><name sortKey="Bodenhofer, U" uniqKey="Bodenhofer U">U. Bodenhofer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Korbel, J O" uniqKey="Korbel J">J. O. Korbel</name></author><author><name sortKey="Abyzov, A" uniqKey="Abyzov A">A. Abyzov</name></author><author><name sortKey="Mu, X J" uniqKey="Mu X">X. J. Mu</name></author><author><name sortKey="Carriero, N" uniqKey="Carriero N">N. Carriero</name></author><author><name sortKey="Cayting, P" uniqKey="Cayting P">P. Cayting</name></author><author><name sortKey="Zhang, Z" uniqKey="Zhang Z">Z. Zhang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Krumm, N" uniqKey="Krumm N">N. Krumm</name></author><author><name sortKey="Sudmant, P H" uniqKey="Sudmant P">P. H. Sudmant</name></author><author><name sortKey="Ko, A" uniqKey="Ko A">A. Ko</name></author><author><name sortKey="O Oak, B J" uniqKey="O Oak B">B. J. O’Roak</name></author><author><name sortKey="Malig, M" uniqKey="Malig M">M. Malig</name></author><author><name sortKey="Coe, B P" uniqKey="Coe B">B. P. Coe</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lam, H Y K" uniqKey="Lam H">H. Y. K. Lam</name></author><author><name sortKey="Pan, C" uniqKey="Pan C">C. Pan</name></author><author><name sortKey="Clark, M J" uniqKey="Clark M">M. J. Clark</name></author><author><name sortKey="Lacroute, P" uniqKey="Lacroute P">P. Lacroute</name></author><author><name sortKey="Chen, R" uniqKey="Chen R">R. Chen</name></author><author><name sortKey="Haraksingh, R" uniqKey="Haraksingh R">R. Haraksingh</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lander, E S" uniqKey="Lander E">E. S. Lander</name></author><author><name sortKey="Linton, L M" uniqKey="Linton L">L. M. Linton</name></author><author><name sortKey="Birren, B" uniqKey="Birren B">B. Birren</name></author><author><name sortKey="Nusbaum, C" uniqKey="Nusbaum C">C. Nusbaum</name></author><author><name sortKey="Zody, M C" uniqKey="Zody M">M. C. Zody</name></author><author><name sortKey="Baldwin, J" uniqKey="Baldwin J">J. Baldwin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Langmead, B" uniqKey="Langmead B">B. Langmead</name></author><author><name sortKey="Trapnell, C" uniqKey="Trapnell C">C. Trapnell</name></author><author><name sortKey="Pop, M" uniqKey="Pop M">M. Pop</name></author><author><name sortKey="Salzberg, S L" uniqKey="Salzberg S">S. L. Salzberg</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lappalainen, I" uniqKey="Lappalainen I">I. Lappalainen</name></author><author><name sortKey="Lopez, J" uniqKey="Lopez J">J. Lopez</name></author><author><name sortKey="Skipper, L" uniqKey="Skipper L">L. Skipper</name></author><author><name sortKey="Hefferon, T" uniqKey="Hefferon T">T. Hefferon</name></author><author><name sortKey="Spalding, J D" uniqKey="Spalding J">J. D. Spalding</name></author><author><name sortKey="Garner, J" uniqKey="Garner J">J. Garner</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Layer, R M" uniqKey="Layer R">R. M. Layer</name></author><author><name sortKey="Chiang, C" uniqKey="Chiang C">C. Chiang</name></author><author><name sortKey="Quinlan, A R" uniqKey="Quinlan A">A. R. Quinlan</name></author><author><name sortKey="Hall, I M" uniqKey="Hall I">I. M. Hall</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lee, E" uniqKey="Lee E">E. Lee</name></author><author><name sortKey="Iskow, R" uniqKey="Iskow R">R. Iskow</name></author><author><name sortKey="Yang, L" uniqKey="Yang L">L. Yang</name></author><author><name sortKey="Gokcumen, O" uniqKey="Gokcumen O">O. Gokcumen</name></author><author><name sortKey="Haseley, P" uniqKey="Haseley P">P. Haseley</name></author><author><name sortKey="Luquette, L J" uniqKey="Luquette L">L. J. Luquette</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lee, S" uniqKey="Lee S">S. Lee</name></author><author><name sortKey="Hormozdiari, F" uniqKey="Hormozdiari F">F. Hormozdiari</name></author><author><name sortKey="Alkan, C" uniqKey="Alkan C">C. Alkan</name></author><author><name sortKey="Brudno, M" uniqKey="Brudno M">M. Brudno</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lee, W P" uniqKey="Lee W">W.-P. Lee</name></author><author><name sortKey="Stromberg, M P" uniqKey="Stromberg M">M. P. Stromberg</name></author><author><name sortKey="Ward, A" uniqKey="Ward A">A. Ward</name></author><author><name sortKey="Stewart, C" uniqKey="Stewart C">C. Stewart</name></author><author><name sortKey="Garrison, E P" uniqKey="Garrison E">E. P. Garrison</name></author><author><name sortKey="Marth, G T" uniqKey="Marth G">G. T. Marth</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Li, H" uniqKey="Li H">H. Li</name></author><author><name sortKey="Durbin, R" uniqKey="Durbin R">R. Durbin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Li, R" uniqKey="Li R">R. Li</name></author><author><name sortKey="Fan, W" uniqKey="Fan W">W. Fan</name></author><author><name sortKey="Tian, G" uniqKey="Tian G">G. Tian</name></author><author><name sortKey="Zhu, H" uniqKey="Zhu H">H. Zhu</name></author><author><name sortKey="He, L" uniqKey="He L">L. He</name></author><author><name sortKey="Cai, J" uniqKey="Cai J">J. Cai</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Li, X" uniqKey="Li X">X. Li</name></author><author><name sortKey="Chen, S" uniqKey="Chen S">S. Chen</name></author><author><name sortKey="Xie, W" uniqKey="Xie W">W. Xie</name></author><author><name sortKey="Vogel, I" uniqKey="Vogel I">I. Vogel</name></author><author><name sortKey="Choy, K W" uniqKey="Choy K">K. W. Choy</name></author><author><name sortKey="Chen, F" uniqKey="Chen F">F. Chen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lin, K" uniqKey="Lin K">K. Lin</name></author><author><name sortKey="Smit, S" uniqKey="Smit S">S. Smit</name></author><author><name sortKey="Bonnema, G" uniqKey="Bonnema G">G. Bonnema</name></author><author><name sortKey="Sanchez Perez, G" uniqKey="Sanchez Perez G">G. Sanchez-Perez</name></author><author><name sortKey="De Ridder, D" uniqKey="De Ridder D">D. de Ridder</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Luo, R" uniqKey="Luo R">R. Luo</name></author><author><name sortKey="Liu, B" uniqKey="Liu B">B. Liu</name></author><author><name sortKey="Xie, Y" uniqKey="Xie Y">Y. Xie</name></author><author><name sortKey="Li, Z" uniqKey="Li Z">Z. Li</name></author><author><name sortKey="Huang, W" uniqKey="Huang W">W. Huang</name></author><author><name sortKey="Yuan, J" uniqKey="Yuan J">J. Yuan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Magi, A" uniqKey="Magi A">A. Magi</name></author><author><name sortKey="Benelli, M" uniqKey="Benelli M">M. Benelli</name></author><author><name sortKey="Marseglia, G" uniqKey="Marseglia G">G. Marseglia</name></author><author><name sortKey="Nannetti, G" uniqKey="Nannetti G">G. Nannetti</name></author><author><name sortKey="Scordo, M R" uniqKey="Scordo M">M. R. Scordo</name></author><author><name sortKey="Torricelli, F" uniqKey="Torricelli F">F. Torricelli</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Magi, A" uniqKey="Magi A">A. Magi</name></author><author><name sortKey="Benelli, M" uniqKey="Benelli M">M. Benelli</name></author><author><name sortKey="Yoon, S" uniqKey="Yoon S">S. Yoon</name></author><author><name sortKey="Roviello, F" uniqKey="Roviello F">F. Roviello</name></author><author><name sortKey="Torricelli, F" uniqKey="Torricelli F">F. Torricelli</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Magi, A" uniqKey="Magi A">A. Magi</name></author><author><name sortKey="Tattini, L" uniqKey="Tattini L">L. Tattini</name></author><author><name sortKey="Cifola, I" uniqKey="Cifola I">I. Cifola</name></author><author><name sortKey="D Urizio, R" uniqKey="D Urizio R">R. D’Aurizio</name></author><author><name sortKey="Benelli, M" uniqKey="Benelli M">M. Benelli</name></author><author><name sortKey="Mangano, E" uniqKey="Mangano E">E. Mangano</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Magi, A" uniqKey="Magi A">A. Magi</name></author><author><name sortKey="Tattini, L" uniqKey="Tattini L">L. Tattini</name></author><author><name sortKey="Pippucci, T" uniqKey="Pippucci T">T. Pippucci</name></author><author><name sortKey="Torricelli, F" uniqKey="Torricelli F">F. Torricelli</name></author><author><name sortKey="Benelli, M" uniqKey="Benelli M">M. Benelli</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Marschall, T" uniqKey="Marschall T">T. Marschall</name></author><author><name sortKey="Costa, I G" uniqKey="Costa I">I. G. Costa</name></author><author><name sortKey="Canzar, S" uniqKey="Canzar S">S. Canzar</name></author><author><name sortKey="Bauer, M" uniqKey="Bauer M">M. Bauer</name></author><author><name sortKey="Klau, G W" uniqKey="Klau G">G. W. Klau</name></author><author><name sortKey="Schliep, A" uniqKey="Schliep A">A. Schliep</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Marschall, T" uniqKey="Marschall T">T. Marschall</name></author><author><name sortKey="Hajirasouliha, I" uniqKey="Hajirasouliha I">I. Hajirasouliha</name></author><author><name sortKey="Schonhuth, A" uniqKey="Schonhuth A">A. Schönhuth</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Medvedev, P" uniqKey="Medvedev P">P. Medvedev</name></author><author><name sortKey="Fiume, M" uniqKey="Fiume M">M. Fiume</name></author><author><name sortKey="Dzamba, M" uniqKey="Dzamba M">M. Dzamba</name></author><author><name sortKey="Smith, T" uniqKey="Smith T">T. Smith</name></author><author><name sortKey="Brudno, M" uniqKey="Brudno M">M. Brudno</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Metzker, M L" uniqKey="Metzker M">M. L. Metzker</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Miller, C A" uniqKey="Miller C">C. A. Miller</name></author><author><name sortKey="Hampton, O" uniqKey="Hampton O">O. Hampton</name></author><author><name sortKey="Coarfa, C" uniqKey="Coarfa C">C. Coarfa</name></author><author><name sortKey="Milosavljevic, A" uniqKey="Milosavljevic A">A. Milosavljevic</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mills, R E" uniqKey="Mills R">R. E. Mills</name></author><author><name sortKey="Luttig, C T" uniqKey="Luttig C">C. T. Luttig</name></author><author><name sortKey="Larkins, C E" uniqKey="Larkins C">C. E. Larkins</name></author><author><name sortKey="Beauchamp, A" uniqKey="Beauchamp A">A. Beauchamp</name></author><author><name sortKey="Tsui, C" uniqKey="Tsui C">C. Tsui</name></author><author><name sortKey="Pittard, W S" uniqKey="Pittard W">W. S. Pittard</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mills, R E" uniqKey="Mills R">R. E. Mills</name></author><author><name sortKey="Walter, K" uniqKey="Walter K">K. Walter</name></author><author><name sortKey="Stewart, C" uniqKey="Stewart C">C. Stewart</name></author><author><name sortKey="Handsaker, R E" uniqKey="Handsaker R">R. E. Handsaker</name></author><author><name sortKey="Chen, K" uniqKey="Chen K">K. Chen</name></author><author><name sortKey="Alkan, C" uniqKey="Alkan C">C. Alkan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mimori, T" uniqKey="Mimori T">T. Mimori</name></author><author><name sortKey="Nariai, N" uniqKey="Nariai N">N. Nariai</name></author><author><name sortKey="Kojima, K" uniqKey="Kojima K">K. Kojima</name></author><author><name sortKey="Takahashi, M" uniqKey="Takahashi M">M. Takahashi</name></author><author><name sortKey="Ono, A" uniqKey="Ono A">A. Ono</name></author><author><name sortKey="Sato, Y" uniqKey="Sato Y">Y. Sato</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mullikin, J C" uniqKey="Mullikin J">J. C. Mullikin</name></author><author><name sortKey="Ning, Z" uniqKey="Ning Z">Z. Ning</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Myers, E W" uniqKey="Myers E">E. W. Myers</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Niedringhaus, T P" uniqKey="Niedringhaus T">T. P. Niedringhaus</name></author><author><name sortKey="Milanova, D" uniqKey="Milanova D">D. Milanova</name></author><author><name sortKey="Kerby, M B" uniqKey="Kerby M">M. B. Kerby</name></author><author><name sortKey="Snyder, M P" uniqKey="Snyder M">M. P. Snyder</name></author><author><name sortKey="Barron, A E" uniqKey="Barron A">A. E. Barron</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nijkamp, J F" uniqKey="Nijkamp J">J. F. Nijkamp</name></author><author><name sortKey="Van Den Broek, M A" uniqKey="Van Den Broek M">M. A. van den Broek</name></author><author><name sortKey="Geertman, J M A" uniqKey="Geertman J">J.-M. A. Geertman</name></author><author><name sortKey="Reinders, M J T" uniqKey="Reinders M">M. J. T. Reinders</name></author><author><name sortKey="Daran, J M G" uniqKey="Daran J">J.-M. G. Daran</name></author><author><name sortKey="De Ridder, D" uniqKey="De Ridder D">D. de Ridder</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ning, Z" uniqKey="Ning Z">Z. Ning</name></author><author><name sortKey="Cox, A J" uniqKey="Cox A">A. J. Cox</name></author><author><name sortKey="Mullikin, J C" uniqKey="Mullikin J">J. C. Mullikin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="O Awe, J A" uniqKey="O Awe J">J. A. O’Rawe</name></author><author><name sortKey="Ferson, S" uniqKey="Ferson S">S. Ferson</name></author><author><name sortKey="Lyon, G J" uniqKey="Lyon G">G. J. Lyon</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pabinger, S" uniqKey="Pabinger S">S. Pabinger</name></author><author><name sortKey="Dander, A" uniqKey="Dander A">A. Dander</name></author><author><name sortKey="Fischer, M" uniqKey="Fischer M">M. Fischer</name></author><author><name sortKey="Snajder, R" uniqKey="Snajder R">R. Snajder</name></author><author><name sortKey="Sperk, M" uniqKey="Sperk M">M. Sperk</name></author><author><name sortKey="Efremova, M" uniqKey="Efremova M">M. Efremova</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pang, A W" uniqKey="Pang A">A. W. Pang</name></author><author><name sortKey="Macdonald, J R" uniqKey="Macdonald J">J. R. MacDonald</name></author><author><name sortKey="Pinto, D" uniqKey="Pinto D">D. Pinto</name></author><author><name sortKey="Wei, J" uniqKey="Wei J">J. Wei</name></author><author><name sortKey="Rafiq, M A" uniqKey="Rafiq M">M. A. Rafiq</name></author><author><name sortKey="Conrad, D F" uniqKey="Conrad D">D. F. Conrad</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pareek, C S" uniqKey="Pareek C">C. S. Pareek</name></author><author><name sortKey="Smoczynski, R" uniqKey="Smoczynski R">R. Smoczynski</name></author><author><name sortKey="Tretyn, A" uniqKey="Tretyn A">A. Tretyn</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pinkel, D" uniqKey="Pinkel D">D. Pinkel</name></author><author><name sortKey="Segraves, R" uniqKey="Segraves R">R. Segraves</name></author><author><name sortKey="Sudar, D" uniqKey="Sudar D">D. Sudar</name></author><author><name sortKey="Clark, S" uniqKey="Clark S">S. Clark</name></author><author><name sortKey="Poole, I" uniqKey="Poole I">I. Poole</name></author><author><name sortKey="Kowbel, D" uniqKey="Kowbel D">D. Kowbel</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Qi, J" uniqKey="Qi J">J. Qi</name></author><author><name sortKey="Zhao, F" uniqKey="Zhao F">F. Zhao</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Quail, M A" uniqKey="Quail M">M. A. Quail</name></author><author><name sortKey="Smith, M" uniqKey="Smith M">M. Smith</name></author><author><name sortKey="Coupland, P" uniqKey="Coupland P">P. Coupland</name></author><author><name sortKey="Otto, T D" uniqKey="Otto T">T. D. Otto</name></author><author><name sortKey="Harris, S R" uniqKey="Harris S">S. R. Harris</name></author><author><name sortKey="Connor, T R" uniqKey="Connor T">T. R. Connor</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Quick, J" uniqKey="Quick J">J. Quick</name></author><author><name sortKey="Quinlan, A R" uniqKey="Quinlan A">A. R. Quinlan</name></author><author><name sortKey="Loman, N J" uniqKey="Loman N">N. J. Loman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Quinlan, A R" uniqKey="Quinlan A">A. R. Quinlan</name></author><author><name sortKey="Clark, R A" uniqKey="Clark R">R. A. Clark</name></author><author><name sortKey="Sokolova, S" uniqKey="Sokolova S">S. Sokolova</name></author><author><name sortKey="Leibowitz, M L" uniqKey="Leibowitz M">M. L. Leibowitz</name></author><author><name sortKey="Zhang, Y" uniqKey="Zhang Y">Y. Zhang</name></author><author><name sortKey="Hurles, M E" uniqKey="Hurles M">M. E. Hurles</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rausch, T" uniqKey="Rausch T">T. Rausch</name></author><author><name sortKey="Zichner, T" uniqKey="Zichner T">T. Zichner</name></author><author><name sortKey="Schlattl, A" uniqKey="Schlattl A">A. Schlattl</name></author><author><name sortKey="Stutz, A M" uniqKey="Stutz A">A. M. Stütz</name></author><author><name sortKey="Benes, V" uniqKey="Benes V">V. Benes</name></author><author><name sortKey="Korbel, J O" uniqKey="Korbel J">J. O. Korbel</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Samarakoon, P S" uniqKey="Samarakoon P">P. S. Samarakoon</name></author><author><name sortKey="Sorte, H S" uniqKey="Sorte H">H. S. Sorte</name></author><author><name sortKey="Kristiansen, B E" uniqKey="Kristiansen B">B. E. Kristiansen</name></author><author><name sortKey="Skodje, T" uniqKey="Skodje T">T. Skodje</name></author><author><name sortKey="Sheng, Y" uniqKey="Sheng Y">Y. Sheng</name></author><author><name sortKey="Tj Nnfjord, G E" uniqKey="Tj Nnfjord G">G. E. Tjønnfjord</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sathirapongsasuti, J F" uniqKey="Sathirapongsasuti J">J. F. Sathirapongsasuti</name></author><author><name sortKey="Lee, H" uniqKey="Lee H">H. Lee</name></author><author><name sortKey="Horst, B A J" uniqKey="Horst B">B. A. J. Horst</name></author><author><name sortKey="Brunner, G" uniqKey="Brunner G">G. Brunner</name></author><author><name sortKey="Cochran, A J" uniqKey="Cochran A">A. J. Cochran</name></author><author><name sortKey="Binder, S" uniqKey="Binder S">S. Binder</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Schadt, E E" uniqKey="Schadt E">E. E. Schadt</name></author><author><name sortKey="Turner, S" uniqKey="Turner S">S. Turner</name></author><author><name sortKey="Kasarskis, A" uniqKey="Kasarskis A">A. Kasarskis</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Schroder, J" uniqKey="Schroder J">J. Schröder</name></author><author><name sortKey="Hsu, A" uniqKey="Hsu A">A. Hsu</name></author><author><name sortKey="Boyle, S E" uniqKey="Boyle S">S. E. Boyle</name></author><author><name sortKey="Macintyre, G" uniqKey="Macintyre G">G. Macintyre</name></author><author><name sortKey="Cmero, M" uniqKey="Cmero M">M. Cmero</name></author><author><name sortKey="Tothill, R W" uniqKey="Tothill R">R. W. Tothill</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sebat, J" uniqKey="Sebat J">J. Sebat</name></author><author><name sortKey="Lakshmi, B" uniqKey="Lakshmi B">B. Lakshmi</name></author><author><name sortKey="Malhotra, D" uniqKey="Malhotra D">D. Malhotra</name></author><author><name sortKey="Troge, J" uniqKey="Troge J">J. Troge</name></author><author><name sortKey="Lese Martin, C" uniqKey="Lese Martin C">C. Lese-Martin</name></author><author><name sortKey="Walsh, T" uniqKey="Walsh T">T. Walsh</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shendure, J" uniqKey="Shendure J">J. Shendure</name></author><author><name sortKey="Ji, H" uniqKey="Ji H">H. Ji</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shendure, J A" uniqKey="Shendure J">J. A. Shendure</name></author><author><name sortKey="Porreca, G J" uniqKey="Porreca G">G. J. Porreca</name></author><author><name sortKey="Church, G M" uniqKey="Church G">G. M. Church</name></author><author><name sortKey="Gardner, A F" uniqKey="Gardner A">A. F. Gardner</name></author><author><name sortKey="Hendrickson, C L" uniqKey="Hendrickson C">C. L. Hendrickson</name></author><author><name sortKey="Kieleczawa, J" uniqKey="Kieleczawa J">J. Kieleczawa</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Simpson, J T" uniqKey="Simpson J">J. T. Simpson</name></author><author><name sortKey="Durbin, R" uniqKey="Durbin R">R. Durbin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Simpson, J T" uniqKey="Simpson J">J. T. Simpson</name></author><author><name sortKey="Durbin, R" uniqKey="Durbin R">R. Durbin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sindi, S" uniqKey="Sindi S">S. Sindi</name></author><author><name sortKey="Helman, E" uniqKey="Helman E">E. Helman</name></author><author><name sortKey="Bashir, A" uniqKey="Bashir A">A. Bashir</name></author><author><name sortKey="Raphael, B J" uniqKey="Raphael B">B. J. Raphael</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sindi, S S" uniqKey="Sindi S">S. S. Sindi</name></author><author><name sortKey="Onal, S" uniqKey="Onal S">S. Onal</name></author><author><name sortKey="Peng, L C" uniqKey="Peng L">L. C. Peng</name></author><author><name sortKey="Wu, H T" uniqKey="Wu H">H.-T. Wu</name></author><author><name sortKey="Raphael, B J" uniqKey="Raphael B">B. J. Raphael</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Snijders, A M" uniqKey="Snijders A">A. M. Snijders</name></author><author><name sortKey="Nowak, N" uniqKey="Nowak N">N. Nowak</name></author><author><name sortKey="Segraves, R" uniqKey="Segraves R">R. Segraves</name></author><author><name sortKey="Blackwood, S" uniqKey="Blackwood S">S. Blackwood</name></author><author><name sortKey="Brown, N" uniqKey="Brown N">N. Brown</name></author><author><name sortKey="Conroy, J" uniqKey="Conroy J">J. Conroy</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tan, R" uniqKey="Tan R">R. Tan</name></author><author><name sortKey="Wang, Y" uniqKey="Wang Y">Y. Wang</name></author><author><name sortKey="Kleinstein, S E" uniqKey="Kleinstein S">S. E. Kleinstein</name></author><author><name sortKey="Liu, Y" uniqKey="Liu Y">Y. Liu</name></author><author><name sortKey="Zhu, X" uniqKey="Zhu X">X. Zhu</name></author><author><name sortKey="Guo, H" uniqKey="Guo H">H. Guo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Teo, S M" uniqKey="Teo S">S. M. Teo</name></author><author><name sortKey="Pawitan, Y" uniqKey="Pawitan Y">Y. Pawitan</name></author><author><name sortKey="Ku, C S" uniqKey="Ku C">C. S. Ku</name></author><author><name sortKey="Chia, K S" uniqKey="Chia K">K. S. Chia</name></author><author><name sortKey="Salim, A" uniqKey="Salim A">A. Salim</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Thung, D" uniqKey="Thung D">D. Thung</name></author><author><name sortKey="De Ligt, J" uniqKey="De Ligt J">J. de Ligt</name></author><author><name sortKey="Vissers, L" uniqKey="Vissers L">L. Vissers</name></author><author><name sortKey="Steehouwer, M" uniqKey="Steehouwer M">M. Steehouwer</name></author><author><name sortKey="Kroon, M" uniqKey="Kroon M">M. Kroon</name></author><author><name sortKey="De Vries, P" uniqKey="De Vries P">P. de Vries</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Trappe, K" uniqKey="Trappe K">K. Trappe</name></author><author><name sortKey="Emde, A K" uniqKey="Emde A">A.-K. Emde</name></author><author><name sortKey="Ehrlich, H C" uniqKey="Ehrlich H">H.-C. Ehrlich</name></author><author><name sortKey="Reinert, K" uniqKey="Reinert K">K. Reinert</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Venkatesan, B M" uniqKey="Venkatesan B">B. M. Venkatesan</name></author><author><name sortKey="Bashir, R" uniqKey="Bashir R">R. Bashir</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Venkatraman, E S" uniqKey="Venkatraman E">E. S. Venkatraman</name></author><author><name sortKey="Olshen, A B" uniqKey="Olshen A">A. B. Olshen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Voelkerding, K V" uniqKey="Voelkerding K">K. V. Voelkerding</name></author><author><name sortKey="Dames, S A" uniqKey="Dames S">S. A. Dames</name></author><author><name sortKey="Durtschi, J D" uniqKey="Durtschi J">J. D. Durtschi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, J" uniqKey="Wang J">J. Wang</name></author><author><name sortKey="Mullighan, C G" uniqKey="Mullighan C">C. G. Mullighan</name></author><author><name sortKey="Easton, J" uniqKey="Easton J">J. Easton</name></author><author><name sortKey="Roberts, S" uniqKey="Roberts S">S. Roberts</name></author><author><name sortKey="Heatley, S L" uniqKey="Heatley S">S. L. Heatley</name></author><author><name sortKey="Ma, J" uniqKey="Ma J">J. Ma</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wong, K" uniqKey="Wong K">K. Wong</name></author><author><name sortKey="Keane, T M" uniqKey="Keane T">T. M. Keane</name></author><author><name sortKey="Stalker, J" uniqKey="Stalker J">J. Stalker</name></author><author><name sortKey="Adams, D J" uniqKey="Adams D">D. J. Adams</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wu, J" uniqKey="Wu J">J. Wu</name></author><author><name sortKey="Lee, W P" uniqKey="Lee W">W.-P. Lee</name></author><author><name sortKey="Ward, A" uniqKey="Ward A">A. Ward</name></author><author><name sortKey="Walker, J A" uniqKey="Walker J">J. A. Walker</name></author><author><name sortKey="Konkel, M K" uniqKey="Konkel M">M. K. Konkel</name></author><author><name sortKey="Batzer, M A" uniqKey="Batzer M">M. A. Batzer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Xi, R" uniqKey="Xi R">R. Xi</name></author><author><name sortKey="Hadjipanayis, A G" uniqKey="Hadjipanayis A">A. G. Hadjipanayis</name></author><author><name sortKey="Luquette, L J" uniqKey="Luquette L">L. J. Luquette</name></author><author><name sortKey="Kim, T M" uniqKey="Kim T">T.-M. Kim</name></author><author><name sortKey="Lee, E" uniqKey="Lee E">E. Lee</name></author><author><name sortKey="Zhang, J" uniqKey="Zhang J">J. Zhang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Xie, C" uniqKey="Xie C">C. Xie</name></author><author><name sortKey="Tammi, M T" uniqKey="Tammi M">M. T. Tammi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ye, K" uniqKey="Ye K">K. Ye</name></author><author><name sortKey="Schulz, M H" uniqKey="Schulz M">M. H. Schulz</name></author><author><name sortKey="Long, Q" uniqKey="Long Q">Q. Long</name></author><author><name sortKey="Apweiler, R" uniqKey="Apweiler R">R. Apweiler</name></author><author><name sortKey="Ning, Z" uniqKey="Ning Z">Z. Ning</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yoon, S" uniqKey="Yoon S">S. Yoon</name></author><author><name sortKey="Xuan, Z" uniqKey="Xuan Z">Z. Xuan</name></author><author><name sortKey="Makarov, V" uniqKey="Makarov V">V. Makarov</name></author><author><name sortKey="Ye, K" uniqKey="Ye K">K. Ye</name></author><author><name sortKey="Sebat, J" uniqKey="Sebat J">J. Sebat</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zeitouni, B" uniqKey="Zeitouni B">B. Zeitouni</name></author><author><name sortKey="Boeva, V" uniqKey="Boeva V">V. Boeva</name></author><author><name sortKey="Janoueix Lerosey, I" uniqKey="Janoueix Lerosey I">I. Janoueix-Lerosey</name></author><author><name sortKey="Loeillet, S" uniqKey="Loeillet S">S. Loeillet</name></author><author><name sortKey="Legoix Ne, P" uniqKey="Legoix Ne P">P. Legoix-né</name></author><author><name sortKey="Nicolas, A" uniqKey="Nicolas A">A. Nicolas</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhang, F" uniqKey="Zhang F">F. Zhang</name></author><author><name sortKey="Gu, W" uniqKey="Gu W">W. Gu</name></author><author><name sortKey="Hurles, M E" uniqKey="Hurles M">M. E. Hurles</name></author><author><name sortKey="Lupski, J R" uniqKey="Lupski J">J. R. Lupski</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhang, J" uniqKey="Zhang J">J. Zhang</name></author><author><name sortKey="Wu, Y" uniqKey="Wu Y">Y. Wu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhao, M" uniqKey="Zhao M">M. Zhao</name></author><author><name sortKey="Wang, Q" uniqKey="Wang Q">Q. Wang</name></author><author><name sortKey="Wang, Q" uniqKey="Wang Q">Q. Wang</name></author><author><name sortKey="Jia, P" uniqKey="Jia P">P. Jia</name></author><author><name sortKey="Zhao, Z" uniqKey="Zhao Z">Z. Zhao</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="review-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Front Bioeng Biotechnol</journal-id><journal-id journal-id-type="iso-abbrev">Front Bioeng Biotechnol</journal-id><journal-id journal-id-type="publisher-id">Front. Bioeng. Biotechnol.</journal-id><journal-title-group><journal-title>Frontiers in Bioengineering and Biotechnology</journal-title></journal-title-group><issn pub-type="epub">2296-4185</issn><publisher><publisher-name>Frontiers Media S.A.</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">26161383</article-id><article-id pub-id-type="pmc">4479793</article-id><article-id pub-id-type="doi">10.3389/fbioe.2015.00092</article-id><article-categories><subj-group subj-group-type="heading"><subject>Bioengineering and Biotechnology</subject><subj-group><subject>Mini Review</subject></subj-group></subj-group></article-categories><title-group><article-title>Detection of Genomic Structural Variants from Next-Generation Sequencing Data</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Tattini</surname><given-names>Lorenzo</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="corresp" rid="cor1">*</xref><uri xlink:type="simple" xlink:href="http://frontiersin.org/people/u/148530"></uri></contrib><contrib contrib-type="author"><name><surname>D’Aurizio</surname><given-names>Romina</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref><uri xlink:type="simple" xlink:href="http://frontiersin.org/people/u/192027"></uri></contrib><contrib contrib-type="author"><name><surname>Magi</surname><given-names>Alberto</given-names></name><xref ref-type="aff" rid="aff3"><sup>3</sup></xref><uri xlink:type="simple" xlink:href="http://frontiersin.org/people/u/125451"></uri></contrib></contrib-group><aff id="aff1"><sup>1</sup><institution>Department of Neurosciences, Psychology, Pharmacology and Child Health, University of Florence</institution>,<addr-line>Florence</addr-line>,<country>Italy</country></aff><aff id="aff2"><sup>2</sup><institution>Laboratory of Integrative Systems Medicine (LISM), Institute of Informatics and Telematics and Institute of Clinical Physiology, National Research Council</institution>,<addr-line>Pisa</addr-line>,<country>Italy</country></aff><aff id="aff3"><sup>3</sup><institution>Department of Clinical and Experimental Medicine, University of Florence</institution>,<addr-line>Florence</addr-line>,<country>Italy</country></aff><author-notes><fn fn-type="edited-by"><p>Edited by: Marco Pellegrini, Consiglio Nazionale delle Ricerche, Italy</p></fn><fn fn-type="edited-by"><p>Reviewed by: Christian Cole, University of Dundee, UK; Alexander Schönhuth, Centrum Wiskunde & Informatica, Netherlands</p></fn><corresp content-type="corresp" id="cor1">*Correspondence: Lorenzo Tattini, Department of Neurosciences, Psychology, Pharmacology and Child Health, University of Florence, Viale Pieraccini, 6, Florence 50139, Italy, <email>lorenzo.tattini@unifi.it</email></corresp><fn fn-type="other" id="fn001"><p>Specialty section: This article was submitted to Bioinformatics and Computational Biology, a section of the journal Frontiers in Bioengineering and Biotechnology</p></fn></author-notes><pub-date pub-type="epub"><day>25</day><month>6</month><year>2015</year></pub-date><pub-date pub-type="collection"><year>2015</year></pub-date><volume>3</volume><elocation-id>92</elocation-id><history><date date-type="received"><day>10</day><month>12</month><year>2014</year></date><date date-type="accepted"><day>10</day><month>6</month><year>2015</year></date></history><permissions><copyright-statement>Copyright © 2015 Tattini, D’Aurizio and Magi.</copyright-statement><copyright-year>2015</copyright-year><copyright-holder>Tattini, D’Aurizio and Magi</copyright-holder><license xlink:href="http://creativecommons.org/licenses/by/4.0/"><license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.</license-p></license></permissions><abstract><p>Structural variants are genomic rearrangements larger than 50 bp accounting for around 1% of the variation among human genomes. They impact on phenotypic diversity and play a role in various diseases including neurological/neurocognitive disorders and cancer development and progression. Dissecting structural variants from next-generation sequencing data presents several challenges and a number of approaches have been proposed in the literature. In this mini review, we describe and summarize the latest tools – and their underlying algorithms – designed for the analysis of whole-genome sequencing, whole-exome sequencing, custom captures, and amplicon sequencing data, pointing out the major advantages/drawbacks. We also report a summary of the most recent applications of third-generation sequencing platforms. This assessment provides a guided indication – with particular emphasis on human genetics and copy number variants – for researchers involved in the investigation of these genomic events.</p></abstract><kwd-group><kwd>next generation sequencing</kwd><kwd>structural variants</kwd><kwd>copy number variants</kwd><kwd>statistical methods</kwd><kwd>whole-exome sequencing</kwd><kwd>whole-genome sequencing</kwd><kwd>amplicon sequencing</kwd></kwd-group><counts><fig-count count="1"></fig-count><table-count count="1"></table-count><equation-count count="0"></equation-count><ref-count count="119"></ref-count><page-count count="8"></page-count><word-count count="7811"></word-count></counts></article-meta></front><body><sec sec-type="introduction" id="S1"><title>Introduction</title><p>Structural variants (SVs) are genomic rearrangements affecting more then 50 bp. The average SV size detected by the 1000 Genomes Project is 8 kbp (1000 Genomes Project Consortium et al., <xref rid="B1" ref-type="bibr">2010</xref>), whereas a study based on tiling CGH array (Conrad et al., <xref rid="B17" ref-type="bibr">2010</xref>) reports a four times larger value. SVs comprise balanced as well as unbalanced events, namely, variants altering the total number of base pairs in a genome. Thus, SVs include deletions, insertions, inversions, mobile-element transpositions, translocations, tandem repeats, and copy number variants (CNVs).</p><p>Several databases – e.g., the Database of Genomic Variants archive which reports structural variation identified in healthy control samples (DGVa<xref ref-type="fn" rid="fn1"><sup>1</sup></xref>) – have been created for the collection of SVs data (Lappalainen et al., <xref rid="B53" ref-type="bibr">2013</xref>). Public data resources have been developed with the purpose of supporting the interpretation of clinically relevant variants, e.g., dbVar<xref ref-type="fn" rid="fn2"><sup>2</sup></xref>, or collecting known disease genes (OMIM<xref ref-type="fn" rid="fn3"><sup>3</sup></xref>) hit by SVs.</p><p>Structural variants account for 1.2% of the variation among human genomes while single nucleotide polymorphisms (SNPs) represent 0.1% (Pang et al., <xref rid="B82" ref-type="bibr">2010</xref>). Notably, unbalanced events provide 99.8% of the entries reported in dbVar (Lin et al., <xref rid="B61" ref-type="bibr">2014</xref>). CNVs may result in benign polymorphic variations or clinical phenotypes due to gene dosage alteration or gene disruption (Zhang et al., <xref rid="B117" ref-type="bibr">2009</xref>). Though the impact of SVs in human genomics was first recognized by their presence in healthy individuals (Zhao et al., <xref rid="B119" ref-type="bibr">2013</xref>), two models account for their association to human disease. Rare large events (<1%, hundreds kbp) have been related to neurological and neurocognitive disorders (Sebat et al., <xref rid="B94" ref-type="bibr">2007</xref>; Girirajan et al., <xref rid="B23" ref-type="bibr">2013</xref>), whereas multicopy gene families, which are commonly copy number variable, contribute to disease susceptibility.</p><p>Next-generation sequencing technologies (NGS) have been revolutionizing genome research [for a survey of NGS tools from quality check to variant annotation and visualization, see Pabinger et al. (<xref rid="B81" ref-type="bibr">2014</xref>)] as well as the study of CNVs (Duan et al., <xref rid="B20" ref-type="bibr">2013</xref>; Zhao et al., <xref rid="B119" ref-type="bibr">2013</xref>; Samarakoon et al., <xref rid="B90" ref-type="bibr">2014</xref>; Tan et al., <xref rid="B102" ref-type="bibr">2014</xref>; Alkodsi et al., <xref rid="B6" ref-type="bibr">2015</xref>; Kadalayil et al., <xref rid="B40" ref-type="bibr">2015</xref>) and SVs on the whole (Alkan et al., <xref rid="B3" ref-type="bibr">2011a</xref>), replacing microarrays as the leading platform for the investigation of genomic rearrangement (Pinkel et al., <xref rid="B84" ref-type="bibr">1998</xref>; Snijders et al., <xref rid="B101" ref-type="bibr">2001</xref>; Iafrate et al., <xref rid="B34" ref-type="bibr">2004</xref>; Sebat et al., <xref rid="B94" ref-type="bibr">2007</xref>). NGS platforms are based on various implementations of cyclic-array sequencing (Shendure and Ji, <xref rid="B95" ref-type="bibr">2008</xref>; Shendure et al., <xref rid="B96" ref-type="bibr">2011</xref>). They allow for the sequencing of millions of short (few hundreds bp) DNA fragments (reads) simultaneously and may process a whole human genome in three days at 500-fold less cost than previous methods (Voelkerding et al., <xref rid="B108" ref-type="bibr">2009</xref>; Metzker, <xref rid="B70" ref-type="bibr">2010</xref>).</p><p>The 1000 Genomes Project applied methods based on all of the four approaches available for the detection of SVs, reporting false discovery rates ranging from 10 to 89%, remarkable differences in terms of genomic regions discovered, size range, and breakpoint precision (Mills et al., <xref rid="B73" ref-type="bibr">2011</xref>; Teo et al., <xref rid="B103" ref-type="bibr">2012</xref>).</p></sec><sec id="S2"><title>Overview of the Approaches</title><p>Four strategies for the detection of SV signatures that are diagnostic of different rearrangements have been reported in the literature (Figure <xref ref-type="fig" rid="F1">1</xref>; Table <xref ref-type="table" rid="T1">1</xref>).</p><fig id="F1" position="float"><label>Figure 1</label><caption><p><bold>Signatures and patterns of SVs for deletion (A), novel sequence insertion (B), inversion (C), and tandem duplication (D) in read count (RC), read-pair (RP), split-read (SR), and <italic>de novo</italic> assembly (AS) methods</bold>.</p></caption><graphic xlink:href="fbioe-03-00092-g001"></graphic></fig><table-wrap id="T1" position="float"><label>Table 1</label><caption><p><bold>A non-exhaustive summary of the tools/algorithms for the investigation of SVs, their input data (WGS, whole-genome sequencing; WES, whole-exome sequencing; CC, custom capture; AMS, amplicon sequencing), and their underling approach</bold>.</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="left" rowspan="1" colspan="1">Tool/algorithm</th><th align="left" rowspan="1" colspan="1">Input data</th><th align="left" rowspan="1" colspan="1">Method</th><th align="left" rowspan="1" colspan="1">Reference</th></tr></thead><tbody><tr><td align="left" rowspan="1" colspan="1">EXCAVATOR</td><td align="left" rowspan="1" colspan="1">WES</td><td align="left" rowspan="1" colspan="1">RC</td><td align="left" rowspan="1" colspan="1">Magi et al. (<xref rid="B65" ref-type="bibr">2013</xref>)</td></tr><tr><td align="left" rowspan="1" colspan="1">ExomeCNV</td><td align="left" rowspan="1" colspan="1">WES</td><td align="left" rowspan="1" colspan="1">RC</td><td align="left" rowspan="1" colspan="1">Sathirapongsasuti et al. (<xref rid="B91" ref-type="bibr">2011</xref>)</td></tr><tr><td align="left" rowspan="1" colspan="1">CoNIFER</td><td align="left" rowspan="1" colspan="1">WES</td><td align="left" rowspan="1" colspan="1">RC</td><td align="left" rowspan="1" colspan="1">Krumm et al. (<xref rid="B49" ref-type="bibr">2012</xref>)</td></tr><tr><td align="left" rowspan="1" colspan="1">CODEX</td><td align="left" rowspan="1" colspan="1">WES</td><td align="left" rowspan="1" colspan="1">RC</td><td align="left" rowspan="1" colspan="1">Jiang et al. (<xref rid="B38" ref-type="bibr">2015</xref>)</td></tr><tr><td align="left" rowspan="1" colspan="1">XHMM</td><td align="left" rowspan="1" colspan="1">WES</td><td align="left" rowspan="1" colspan="1">RC</td><td align="left" rowspan="1" colspan="1">Fromer et al. (<xref rid="B22" ref-type="bibr">2012</xref>)</td></tr><tr><td align="left" rowspan="1" colspan="1">–</td><td align="left" rowspan="1" colspan="1">WES/CC</td><td align="left" rowspan="1" colspan="1">RC</td><td align="left" rowspan="1" colspan="1">Bansal et al. (<xref rid="B8" ref-type="bibr">2014</xref>)</td></tr><tr><td align="left" rowspan="1" colspan="1">ONCOCNV</td><td align="left" rowspan="1" colspan="1">AMS</td><td align="left" rowspan="1" colspan="1">RC</td><td align="left" rowspan="1" colspan="1">Boeva et al. (<xref rid="B11" ref-type="bibr">2014</xref>)</td></tr><tr><td align="left" rowspan="1" colspan="1">CNVnator</td><td align="left" rowspan="1" colspan="1">WGS</td><td align="left" rowspan="1" colspan="1">RC</td><td align="left" rowspan="1" colspan="1">Abyzov et al. (<xref rid="B2" ref-type="bibr">2011</xref>)</td></tr><tr><td align="left" rowspan="1" colspan="1">SegSeq</td><td align="left" rowspan="1" colspan="1">WGS</td><td align="left" rowspan="1" colspan="1">RC</td><td align="left" rowspan="1" colspan="1">Chiang et al. (<xref rid="B16" ref-type="bibr">2009</xref>)</td></tr><tr><td align="left" rowspan="1" colspan="1">CNAnorm</td><td align="left" rowspan="1" colspan="1">WGS</td><td align="left" rowspan="1" colspan="1">RC</td><td align="left" rowspan="1" colspan="1">Gusnanto et al. (<xref rid="B25" ref-type="bibr">2012</xref>)</td></tr><tr><td align="left" rowspan="1" colspan="1">CNAseg</td><td align="left" rowspan="1" colspan="1">WGS</td><td align="left" rowspan="1" colspan="1">RC</td><td align="left" rowspan="1" colspan="1">Ivakhno et al. (<xref rid="B36" ref-type="bibr">2010</xref>)</td></tr><tr><td align="left" rowspan="1" colspan="1">rSW-seq</td><td align="left" rowspan="1" colspan="1">WGS</td><td align="left" rowspan="1" colspan="1">RC</td><td align="left" rowspan="1" colspan="1">Kim et al. (<xref rid="B46" ref-type="bibr">2010</xref>)</td></tr><tr><td align="left" rowspan="1" colspan="1">cn.MOPS</td><td align="left" rowspan="1" colspan="1">WGS</td><td align="left" rowspan="1" colspan="1">RC</td><td align="left" rowspan="1" colspan="1">Klambauer et al. (<xref rid="B47" ref-type="bibr">2012</xref>)</td></tr><tr><td align="left" rowspan="1" colspan="1">JointSLM</td><td align="left" rowspan="1" colspan="1">WGS</td><td align="left" rowspan="1" colspan="1">RC</td><td align="left" rowspan="1" colspan="1">Magi et al. (<xref rid="B64" ref-type="bibr">2011</xref>)</td></tr><tr><td align="left" rowspan="1" colspan="1">ReadDepth</td><td align="left" rowspan="1" colspan="1">WGS</td><td align="left" rowspan="1" colspan="1">RC</td><td align="left" rowspan="1" colspan="1">Miller et al. (<xref rid="B71" ref-type="bibr">2011</xref>)</td></tr><tr><td align="left" rowspan="1" colspan="1">BIC-seq</td><td align="left" rowspan="1" colspan="1">WGS</td><td align="left" rowspan="1" colspan="1">RC</td><td align="left" rowspan="1" colspan="1">Xi et al. (<xref rid="B112" ref-type="bibr">2011</xref>)</td></tr><tr><td align="left" rowspan="1" colspan="1">PSCC</td><td align="left" rowspan="1" colspan="1">WGS</td><td align="left" rowspan="1" colspan="1">RC</td><td align="left" rowspan="1" colspan="1">Li et al. (<xref rid="B60" ref-type="bibr">2014</xref>)</td></tr><tr><td align="left" rowspan="1" colspan="1">CNV-seq</td><td align="left" rowspan="1" colspan="1">WGS</td><td align="left" rowspan="1" colspan="1">RC</td><td align="left" rowspan="1" colspan="1">Xie and Tammi (<xref rid="B113" ref-type="bibr">2009</xref>)</td></tr><tr><td align="left" rowspan="1" colspan="1">CLEVER</td><td align="left" rowspan="1" colspan="1">WGS</td><td align="left" rowspan="1" colspan="1">RP</td><td align="left" rowspan="1" colspan="1">Marschall et al. (<xref rid="B67" ref-type="bibr">2012</xref>)</td></tr><tr><td align="left" rowspan="1" colspan="1">BreakDancer</td><td align="left" rowspan="1" colspan="1">WGS</td><td align="left" rowspan="1" colspan="1">RP</td><td align="left" rowspan="1" colspan="1">Chen et al. (<xref rid="B15" ref-type="bibr">2009</xref>)</td></tr><tr><td align="left" rowspan="1" colspan="1">VariationHunter</td><td align="left" rowspan="1" colspan="1">WGS</td><td align="left" rowspan="1" colspan="1">RP</td><td align="left" rowspan="1" colspan="1">Hormozdiari et al. (<xref rid="B33" ref-type="bibr">2011</xref>)</td></tr><tr><td align="left" rowspan="1" colspan="1">PEMer</td><td align="left" rowspan="1" colspan="1">WGS</td><td align="left" rowspan="1" colspan="1">RP</td><td align="left" rowspan="1" colspan="1">Korbel et al. (<xref rid="B48" ref-type="bibr">2009</xref>)</td></tr><tr><td align="left" rowspan="1" colspan="1">MoDIL</td><td align="left" rowspan="1" colspan="1">WGS</td><td align="left" rowspan="1" colspan="1">RP</td><td align="left" rowspan="1" colspan="1">Lee et al. (<xref rid="B56" ref-type="bibr">2009</xref>)</td></tr><tr><td align="left" rowspan="1" colspan="1">Gustaf</td><td align="left" rowspan="1" colspan="1">WGS</td><td align="left" rowspan="1" colspan="1">SR</td><td align="left" rowspan="1" colspan="1">Trappe et al. (<xref rid="B105" ref-type="bibr">2014</xref>)</td></tr><tr><td align="left" rowspan="1" colspan="1">Socrates</td><td align="left" rowspan="1" colspan="1">WGS</td><td align="left" rowspan="1" colspan="1">SR</td><td align="left" rowspan="1" colspan="1">Schröder et al. (<xref rid="B93" ref-type="bibr">2014</xref>)</td></tr><tr><td align="left" rowspan="1" colspan="1">Splitread</td><td align="left" rowspan="1" colspan="1">WGS/WES</td><td align="left" rowspan="1" colspan="1">SR</td><td align="left" rowspan="1" colspan="1">Karakoc et al. (<xref rid="B41" ref-type="bibr">2012</xref>)</td></tr><tr><td align="left" rowspan="1" colspan="1">Cortex</td><td align="left" rowspan="1" colspan="1">WGS</td><td align="left" rowspan="1" colspan="1">AS</td><td align="left" rowspan="1" colspan="1">Iqbal et al. (<xref rid="B35" ref-type="bibr">2012</xref>)</td></tr><tr><td align="left" rowspan="1" colspan="1">Magnolya</td><td align="left" rowspan="1" colspan="1">WGS</td><td align="left" rowspan="1" colspan="1">AS</td><td align="left" rowspan="1" colspan="1">Nijkamp et al. (<xref rid="B78" ref-type="bibr">2012</xref>)</td></tr><tr><td align="left" rowspan="1" colspan="1">Tea</td><td align="left" rowspan="1" colspan="1">WGS</td><td align="left" rowspan="1" colspan="1">DC</td><td align="left" rowspan="1" colspan="1">Lee et al. (<xref rid="B55" ref-type="bibr">2012</xref>)</td></tr><tr><td align="left" rowspan="1" colspan="1">RetroSeq</td><td align="left" rowspan="1" colspan="1">WGS</td><td align="left" rowspan="1" colspan="1">DC</td><td align="left" rowspan="1" colspan="1">Keane et al. (<xref rid="B42" ref-type="bibr">2013</xref>)</td></tr><tr><td align="left" rowspan="1" colspan="1">Tangram</td><td align="left" rowspan="1" colspan="1">WGS</td><td align="left" rowspan="1" colspan="1">DC</td><td align="left" rowspan="1" colspan="1">Wu et al. (<xref rid="B111" ref-type="bibr">2014</xref>)</td></tr><tr><td align="left" rowspan="1" colspan="1">Mobster</td><td align="left" rowspan="1" colspan="1">WGS/WES</td><td align="left" rowspan="1" colspan="1">DC</td><td align="left" rowspan="1" colspan="1">Keane et al. (<xref rid="B42" ref-type="bibr">2013</xref>)</td></tr><tr><td align="left" colspan="4" rowspan="1"><hr></hr></td></tr><tr><td align="left" rowspan="1" colspan="1">SVDetect</td><td align="left" rowspan="1" colspan="1">WGS</td><td align="left" rowspan="1" colspan="1">RC + RP</td><td align="left" rowspan="1" colspan="1">Zeitouni et al. (<xref rid="B116" ref-type="bibr">2010</xref>)</td></tr><tr><td align="left" rowspan="1" colspan="1">GASVpro</td><td align="left" rowspan="1" colspan="1">WGS</td><td align="left" rowspan="1" colspan="1">RC + RP</td><td align="left" rowspan="1" colspan="1">Sindi et al. (<xref rid="B100" ref-type="bibr">2012</xref>)</td></tr><tr><td align="left" rowspan="1" colspan="1">CNVer</td><td align="left" rowspan="1" colspan="1">WGS</td><td align="left" rowspan="1" colspan="1">RC + RP</td><td align="left" rowspan="1" colspan="1">Medvedev et al. (<xref rid="B69" ref-type="bibr">2010</xref>)</td></tr><tr><td align="left" rowspan="1" colspan="1">inGAP-sv</td><td align="left" rowspan="1" colspan="1">WGS</td><td align="left" rowspan="1" colspan="1">RC + RP</td><td align="left" rowspan="1" colspan="1">Qi and Zhao (<xref rid="B85" ref-type="bibr">2011</xref>)</td></tr><tr><td align="left" rowspan="1" colspan="1">Pindel</td><td align="left" rowspan="1" colspan="1">WGS</td><td align="left" rowspan="1" colspan="1">RP + SR</td><td align="left" rowspan="1" colspan="1">Ye et al. (<xref rid="B114" ref-type="bibr">2009</xref>)</td></tr><tr><td align="left" rowspan="1" colspan="1">LUMPY</td><td align="left" rowspan="1" colspan="1">WGS</td><td align="left" rowspan="1" colspan="1">RP + SR</td><td align="left" rowspan="1" colspan="1">Layer et al. (<xref rid="B54" ref-type="bibr">2014</xref>)</td></tr><tr><td align="left" rowspan="1" colspan="1">DELLY</td><td align="left" rowspan="1" colspan="1">WGS</td><td align="left" rowspan="1" colspan="1">RP + SR</td><td align="left" rowspan="1" colspan="1">Rausch et al. (<xref rid="B89" ref-type="bibr">2012</xref>)</td></tr><tr><td align="left" rowspan="1" colspan="1">PRISM</td><td align="left" rowspan="1" colspan="1">WGS</td><td align="left" rowspan="1" colspan="1">RP + SR</td><td align="left" rowspan="1" colspan="1">Jiang et al. (<xref rid="B39" ref-type="bibr">2012</xref>)</td></tr><tr><td align="left" rowspan="1" colspan="1">MATE-CLEVER</td><td align="left" rowspan="1" colspan="1">WGS</td><td align="left" rowspan="1" colspan="1">RP + SR</td><td align="left" rowspan="1" colspan="1">Marschall et al. (<xref rid="B68" ref-type="bibr">2013</xref>)</td></tr><tr><td align="left" rowspan="1" colspan="1">NovelSeq</td><td align="left" rowspan="1" colspan="1">WGS</td><td align="left" rowspan="1" colspan="1">RP + AS</td><td align="left" rowspan="1" colspan="1">Hajirasouliha et al. (<xref rid="B27" ref-type="bibr">2010</xref>)</td></tr><tr><td align="left" rowspan="1" colspan="1">HYDRA</td><td align="left" rowspan="1" colspan="1">WGS</td><td align="left" rowspan="1" colspan="1">RP + AS</td><td align="left" rowspan="1" colspan="1">Quinlan et al. (<xref rid="B88" ref-type="bibr">2010</xref>)</td></tr><tr><td align="left" rowspan="1" colspan="1">CREST</td><td align="left" rowspan="1" colspan="1">WGS</td><td align="left" rowspan="1" colspan="1">SR + AS</td><td align="left" rowspan="1" colspan="1">Wang et al. (<xref rid="B109" ref-type="bibr">2011</xref>)</td></tr><tr><td align="left" rowspan="1" colspan="1">SVseq</td><td align="left" rowspan="1" colspan="1">WGS</td><td align="left" rowspan="1" colspan="1">RC + SR</td><td align="left" rowspan="1" colspan="1">Zhang and Wu (<xref rid="B118" ref-type="bibr">2011</xref>)</td></tr><tr><td align="left" rowspan="1" colspan="1">SoftSearch</td><td align="left" rowspan="1" colspan="1">WGS/WES/CC</td><td align="left" rowspan="1" colspan="1">RP + SR</td><td align="left" rowspan="1" colspan="1">Hart et al. (<xref rid="B30" ref-type="bibr">2013</xref>)</td></tr><tr><td align="left" rowspan="1" colspan="1">Genome STRiP</td><td align="left" rowspan="1" colspan="1">WGS</td><td align="left" rowspan="1" colspan="1">RP + SR + RC</td><td align="left" rowspan="1" colspan="1">Handsaker et al. (<xref rid="B28" ref-type="bibr">2011</xref>)</td></tr></tbody></table><table-wrap-foot><p><italic>Methods designed using WGS data can, in principle, be used with WES data, though with limitations due to the intrinsic sparseness of WES data</italic>.</p></table-wrap-foot></table-wrap><p>Read-pair (RP) methods are based on the evaluation of the span and orientation of paired-end reads. Discordant pairs in which the mapping span and/or orientation of the read pairs are inconsistent with the expected insert size are collected. Several classes of SVs can be investigated by means of this approach. Read pairs mapping too far apart are associated to deletions while those found closer than expected are indicative of insertions. Furthermore, orientation inconsistencies can represent inversions and a specific class of tandem duplications.</p><p>Read-depth (or read count, RC) approaches assume a random (Poisson or modified Poisson) distribution in mapping depth and investigate the divergence from this distribution to highlight duplications and deletions (Magi et al., <xref rid="B66" ref-type="bibr">2012</xref>). Sequencing of duplicated/amplified regions results in higher read depth while deleted regions show reduced read depth when compared to normal (e.g., diploid) regions.</p><p>Split-read (SR) methods allow for the detection of SVs with single base-pair resolution. The presence of a SV breakpoint is investigated on the basis of a split sequence-read signature breaking the alignment to the reference. A gap in the read is a marker of a deletion while stretches in the reference reflect insertions.</p><p>Theoretically, all forms of structural variation could be investigated by means of <italic>de novo</italic> assembly (AS) methods. <italic>De novo</italic> assembly refers to merging and ordering short fragments to reassemble the original sequence from which the short fragments were sampled (Earl et al., <xref rid="B21" ref-type="bibr">2011</xref>). NGS data intrinsic characteristics, such as (short) read length, limit the use of AS approaches for variant investigation.</p><p>Moreover, a specific class of SV, mobile elements (ME) insertions, can be investigated exploiting discordant and clipped (DC) read information.</p></sec><sec id="S3"><title>Read Count Methods</title><p>Read count is suitable for the investigation of CNVs. RC methods comprise four steps: RC data preparation, data normalization, SV regions identification, and copy number estimation. Reads mapping to windows/bins of fixed size are counted (Yoon et al., <xref rid="B115" ref-type="bibr">2009</xref>; Magi et al., <xref rid="B64" ref-type="bibr">2011</xref>) and the results are normalized for the mitigation of local GC content and mappability effects.</p><p>The correlation between local GC content and read coverage has been detected through the analysis of data from several platforms (Harismendy et al., <xref rid="B29" ref-type="bibr">2009</xref>). Mappability bias is due to repetitive regions within the human genome (Miller et al., <xref rid="B71" ref-type="bibr">2011</xref>).</p><p>A segmentation step is necessary to split RC signal into segments characterized by a constant DNA copy number. Algorithms conceived for aCGH data such as the circular binary segmentation (CBS) algorithm (Campbell et al., <xref rid="B12" ref-type="bibr">2008</xref>; Miller et al., <xref rid="B71" ref-type="bibr">2011</xref>) and those based on hidden Markov models (HMM) (Magi et al., <xref rid="B63" ref-type="bibr">2010</xref>) are used with this scope.</p><p>Copy number estimation can be tackled by means of two strategies. Both assume that the sequencing process is uniform. Thus, the number of reads mapping to a genomic region is expected to be proportional to the number of times the regions appears in the DNA sample. Three methods (Campbell et al., <xref rid="B12" ref-type="bibr">2008</xref>; Yoon et al., <xref rid="B115" ref-type="bibr">2009</xref>; Magi et al., <xref rid="B64" ref-type="bibr">2011</xref>) estimate DNA copy number of all the detected regions rounding the median RCs (normalized to copy number 2) to the nearest integer, while CNVnator (Abyzov et al., <xref rid="B2" ref-type="bibr">2011</xref>) uses RC signal normalized to the genomic average for the regions of the same length.</p><p>A considerable number of methods for the detection of CNV in whole-genome sequencing (WGS) data have been reported in the literature, including CNVnator, CNAnorm, CNAseg, rSW-seq, cn.MOPS, JointSLM, ReadDepth, and BIC-seq (Ivakhno et al., <xref rid="B36" ref-type="bibr">2010</xref>; Kim et al., <xref rid="B46" ref-type="bibr">2010</xref>; Abyzov et al., <xref rid="B2" ref-type="bibr">2011</xref>; Magi et al., <xref rid="B64" ref-type="bibr">2011</xref>; Miller et al., <xref rid="B71" ref-type="bibr">2011</xref>; Xi et al., <xref rid="B112" ref-type="bibr">2011</xref>; Gusnanto et al., <xref rid="B25" ref-type="bibr">2012</xref>; Klambauer et al., <xref rid="B47" ref-type="bibr">2012</xref>). Recently, PSCC (Li et al., <xref rid="B60" ref-type="bibr">2014</xref>) has been compared with SegSeq (Chiang et al., <xref rid="B16" ref-type="bibr">2009</xref>) and ReadDepth (Miller et al., <xref rid="B71" ref-type="bibr">2011</xref>).</p><sec id="S3-1"><title>CNV detection from whole-exome data</title><p>Due to the costs associated to WGS, the investigation of CNVs using whole-exome sequencing (WES) data is definitely an attractive perspective. Nevertheless, the sparse nature of the target and the non-uniform read-depth among captured regions make CNV detection from WES data awkward with respect to WGS [in particular, regarding the segmentation step as reported in Magi et al. (<xref rid="B65" ref-type="bibr">2013</xref>)].</p><p>Several tools have been reported in the literature for this purpose including ExomeCNV (Sathirapongsasuti et al., <xref rid="B91" ref-type="bibr">2011</xref>), CoNIFER (Krumm et al., <xref rid="B49" ref-type="bibr">2012</xref>), CNV-seq (Xie and Tammi, <xref rid="B113" ref-type="bibr">2009</xref>), XHMM (Fromer et al., <xref rid="B22" ref-type="bibr">2012</xref>), and recently EXCAVATOR (Magi et al., <xref rid="B65" ref-type="bibr">2013</xref>) and CODEX (Jiang et al., <xref rid="B38" ref-type="bibr">2015</xref>). Notably, the method developed by Bansal and co-workers (Bansal et al., <xref rid="B8" ref-type="bibr">2014</xref>) allows for the analysis of NGS data generated from small subsets of the exome, namely custom capture (CC) data.</p></sec><sec id="S3-2"><title>Amplicon sequencing data</title><p>Amplicon sequencing (AMS) techniques have been reported in the literature in particular for clinical applications (Desai and Jere, <xref rid="B19" ref-type="bibr">2012</xref>; Beadling et al., <xref rid="B10" ref-type="bibr">2013</xref>).</p><p>Amplicon sequencing data show different biases in respect of WES data (Boeva et al., <xref rid="B11" ref-type="bibr">2014</xref>). Data normalization can be less effective due to the limited number of target regions. Furthermore, protocols involved in the preparation of amplicon libraries result in high depth of coverage at the expense of coverage homogeneity.</p><p>The first method designed for the investigation of CNV from AMS data is ONCOCNV. Duplicate sequences are not removed, while RC is performed assigning “each read to only one amplicon region, the one with which the read alignment has the maximum overlap” (Boeva et al., <xref rid="B11" ref-type="bibr">2014</xref>).</p><p>Data are then normalized with respect to library size assuming a similar efficiency of PCR amplification for all the targeted regions. GC content and amplicon length biases are corrected by means of a local polynomial regression fitting. Principal component analysis (PCA) is employed to construct a baseline reflecting the technological bias in control samples. The baseline is calculated by means of the first three principal components (calculated from control samples data). In order to define a significant threshold to call a copy number change, the standard deviation of the normalized RCs for each amplicon region is calculated.</p><p>This procedure is applied to data from test samples keeping the residuals of the linear regression of normalized RCs over the baseline calculated for the control samples.</p><p>Segmentation of the resulting signal profile is performed with CBS method (Venkatraman and Olshen, <xref rid="B107" ref-type="bibr">2007</xref>). A segmentation and clustering approach (SCA) is used to define the copy number state (neutral, gain, or loss) of the segmented regions.</p></sec></sec><sec id="S4"><title>Read-pair algorithms</title><p>As already mentioned, RP methods, as well as SR approaches, are suitable for the detection of several classes of SV including insertions of novel sequences and inversions. Notably, RP algorithms cannot detect the signatures of novel sequence insertions larger than the average insert size. Several tools based on the detection of SV signatures from <italic>clusters</italic> of read-pairs have been reported in the literature including BreakDancer, VariationHunter, PEMer, and GASV (Chen et al., <xref rid="B15" ref-type="bibr">2009</xref>; Hormozdiari et al., <xref rid="B31" ref-type="bibr">2009</xref>, <xref rid="B33" ref-type="bibr">2011</xref>; Korbel et al., <xref rid="B48" ref-type="bibr">2009</xref>; Sindi et al., <xref rid="B99" ref-type="bibr">2009</xref>). Remarkably, PEMer can be exploited for the identification of linked insertions (Medvedev et al., <xref rid="B69" ref-type="bibr">2010</xref>).</p><p>Clusters can be defined according to two strategies. The standard clustering strategy relies on two parameters: the minimum number of pairs with similar signature and the maximum value of the mean insert size standard deviation for a pair to be considered concordant. The maximum standard deviation value is fixed and events spanning the same locus, resulting in a small value of the insert size standard deviation, may be missed.</p><p>Distribution-based approaches, e.g., MoDIL (Lee et al., <xref rid="B56" ref-type="bibr">2009</xref>), exploit the local distribution of all the mappings spanning a particular location on the genome. A read cluster is generated when the local distribution is shifted in respect to the typical insert size distribution. This approach allows for the detection of smaller events (e.g., compared with VariationHunter). The presence of two superimposed insert size distributions can be also detected, thus allowing for the discrimination of homozygous and heterozygous variants.</p><p>In the first implementations of the approach, e.g., BreakDancer (Chen et al., <xref rid="B15" ref-type="bibr">2009</xref>), reads with multiple mappings were discarded. Thus, repetitive regions of the genome (including segmental duplications and copy-number amplifications) could not be investigated. Notably, BreakDancer allows for the identification of inter- and intra-chromosomal translocations. Tools such as MoDIL and VariationHunter or, more recently, CLEVER (Marschall et al., <xref rid="B67" ref-type="bibr">2012</xref>) deal with multiple mapping reads [aligned, for instance, with mrFast (Alkan et al., <xref rid="B5" ref-type="bibr">2009</xref>), Mosaik (Lee et al., <xref rid="B57" ref-type="bibr">2014</xref>), BWA (Li and Durbin, <xref rid="B58" ref-type="bibr">2010</xref>), or Bowtie (Langmead et al., <xref rid="B52" ref-type="bibr">2009</xref>)]. CLEVER uses an insert size-based approach to build a graph with all reads and evaluates SV from maximal cliques. It is particularly well-tuned for the investigation of insertions and deletions of 50–100 bp.</p></sec><sec id="S5"><title>Split-read approaches</title><p>Though SR methods were conceived for Sanger sequencing reads (Mills et al., <xref rid="B72" ref-type="bibr">2006</xref>), algorithms such as Pindel, Splitread, and Gustaf (Ye et al., <xref rid="B114" ref-type="bibr">2009</xref>; Karakoc et al., <xref rid="B41" ref-type="bibr">2012</xref>; Trappe et al., <xref rid="B105" ref-type="bibr">2014</xref>) use paired-end NGS reads to identify SVs (or indel) events. SR approaches take advantage of one-end anchored reads, namely those pairs in which “one end is anchored to the reference genome and the other end maps imprecisely owing to the presence of an underlying structural variant or indel breakpoint” (Karakoc et al., <xref rid="B41" ref-type="bibr">2012</xref>). SR-based tools can be applied solely to unique reference regions.</p><p>Pindel uses pattern growth for optimal matching in target regions, exploiting reads mapped with SSAHA2 [Sequence Search and Alignment by Hashing Algorithm, Ning et al. (<xref rid="B79" ref-type="bibr">2001</xref>)], BWA, or Mosaik. It must be stressed that the latest version of Pindel integrates RP to the SR information (Lin et al., <xref rid="B61" ref-type="bibr">2014</xref>). Splitread searches for clusters of split reads using balanced splits as seeds. Splitread can detect, at least in theory, deletions without size limitation, while for insertions the size spectrum depends on the sequencing library. Insertions shorter than the read length can be accurately identified but larger insertions can only be approximately characterized within the insert size (Karakoc et al., <xref rid="B41" ref-type="bibr">2012</xref>). Splitread is suitable for WGS/WES reads aligned using mrsFAST (Hach et al., <xref rid="B26" ref-type="bibr">2010</xref>) to discover indels, SVs, <italic>de novo</italic> events, and pseudogenes.</p><p>Recently, Socrates (a SR method designed for cancer genomics) was compared to several tools (Schröder et al., <xref rid="B93" ref-type="bibr">2014</xref>), including BreakDancer, CLEVER, CREST (Wang et al., <xref rid="B109" ref-type="bibr">2011</xref>), DELLY (Rausch et al., <xref rid="B89" ref-type="bibr">2012</xref>), Pindel, and PRISM (Jiang et al., <xref rid="B39" ref-type="bibr">2012</xref>).</p></sec><sec id="S6"><title>Assembly based tools</title><p><italic>De novo</italic> assembly allows – at least in principle – for the detection of all the forms of structural variation but the application of this approach is still challenging due to the limited length of NGS reads (Alkan et al., <xref rid="B3" ref-type="bibr">2011a</xref>; O’Rawe et al., <xref rid="B80" ref-type="bibr">2015</xref>).</p><p>AS methods were first exploited for Sanger sequencing data (characterized by read length between 300 and 1000 bp). The original <italic>string graph approach</italic> has been extended to de Bruijn graphs. The Assemblathon competition (Earl et al., <xref rid="B21" ref-type="bibr">2011</xref>) produced a detailed comparison among <italic>de novo</italic> assemblers, including Phusion2 (Mullikin and Ning, <xref rid="B75" ref-type="bibr">2003</xref>), SGA (Simpson and Durbin, <xref rid="B97" ref-type="bibr">2010</xref>, <xref rid="B98" ref-type="bibr">2012</xref>), Quake (Kelley et al., <xref rid="B43" ref-type="bibr">2010</xref>), the first implementation of SOAPdenovo (Li et al., <xref rid="B59" ref-type="bibr">2010</xref>; Luo et al., <xref rid="B62" ref-type="bibr">2012</xref>), and ALLPATHS-LG (Gnerre et al., <xref rid="B24" ref-type="bibr">2011</xref>), based on simulated data.</p><p>Two AS based callers have been reported in the literature for the investigation of SVs. Magnolya (Nijkamp et al., <xref rid="B78" ref-type="bibr">2012</xref>) uses a Poisson mixture model (PMM) for CNV detection from contigs co-assembled from NGS sequencing data. The authors use an overlap-layout-consensus assembler to generate a contig string graph. Contig string graphs are characterized by nodes representing reads and edges representing an overlap. The final form of the graph is produced by transitive reduction – which removes redundant edges – and by unitigging (i.e., collapsing simple paths without branches) (Myers, <xref rid="B76" ref-type="bibr">2005</xref>). In the resulting contig string graph, each node represents a collapsed set of reads called <italic>contig</italic>. Finally, the PMM approach for modeling read count is introduced to estimate the copy number of a contig. Once the model has been corrected for the presence of repetitive regions in the genome and prior knowledge on ploidy has been included, the model with the optimal number of Poisson distributions is selected by means of the lowest Bayesian information criterion. Integer copy numbers can be thus inferred by maximum <italic>a posteriori</italic> estimation. Remarkably, the method can be applied when no reference is available but – as already stressed – it is limited by the short read length typical of NGS platforms.</p><p>Cortex uses colored de Bruijn graphs with colors of both edges and nodes representing different samples and, possibly, reference sequences or known variants to assemble NGS reads. “The graph consists of a set of nodes representing words of length <italic>k</italic> (<italic>k</italic>-mers). Directed edges join <italic>k</italic>-mers seen consecutively in the input” (Iqbal et al., <xref rid="B35" ref-type="bibr">2012</xref>). The package includes four algorithms for variant discovery. For example, the <italic>bubble calling</italic> algorithm may be exploited for the detection of variant bubbles in a colored de Bruijn graph from a single diploid individual. It must be stressed that using a reference genome aids the identification of variants while it is indispensable for the investigation of homozygous variant sites. Nevertheless, the sensitivity of the method decreases with the size of the variant. The tool has been extensively tested on human data.</p></sec><sec id="S7"><title>Combined Methods</title><p>None of the aforementioned approaches is capable of capturing the full spectrum of SV events with high sensitivity and specificity. RC methods can accurately predict absolute copy numbers but the breakpoint resolution is often inadequate and events such as inversions and novel sequence insertions cannot be detected. On the other hand, RP and SR approaches show low sensitivity in repetitive regions. Several packages combining different approaches for the investigation of SVs have been reported.</p><p>Combining RC for the detection of large events and RP for accurate identification of breakpoints can reduce the number of false positive calls [SVDetect (Zeitouni et al., <xref rid="B116" ref-type="bibr">2010</xref>), CNVer (Medvedev et al., <xref rid="B69" ref-type="bibr">2010</xref>), GASVPro (Sindi et al., <xref rid="B100" ref-type="bibr">2012</xref>), and inGAP-sv (Qi and Zhao, <xref rid="B85" ref-type="bibr">2011</xref>)]. Genome STRiP (Handsaker et al., <xref rid="B28" ref-type="bibr">2011</xref>) exploits RP, RC, SR, and population-scale patterns to detect genome structural polymorphisms.</p><p>Packages implementing RP and (local) AS have been also reported [NovelSeq (Hajirasouliha et al., <xref rid="B27" ref-type="bibr">2010</xref>), HYDRA (Quinlan et al., <xref rid="B88" ref-type="bibr">2010</xref>)] as well as tools exploiting SR and RC/RP such as SVseq, MATE-CLEVER, and PRISM (Zhang and Wu, <xref rid="B118" ref-type="bibr">2011</xref>; Jiang et al., <xref rid="B39" ref-type="bibr">2012</xref>; Marschall et al., <xref rid="B68" ref-type="bibr">2013</xref>). PRISM was tested on simulated data and compared with Pindel, SVseq, Splitread, and CREST. Notably, DELLY is suitable for detecting copy-number variable deletion and tandem duplication events as well as balanced rearrangements such as inversions or reciprocal translocations (Rausch et al., <xref rid="B89" ref-type="bibr">2012</xref>), while SoftSearch (Hart et al., <xref rid="B30" ref-type="bibr">2013</xref>) is designed for WGS, WES, and CC data. Recently, LUMPY has been shown to be “especially pronounced when evidence is scarce, either due to low coverage data or low variant allele frequency” (Layer et al., <xref rid="B54" ref-type="bibr">2014</xref>). LUMPY is designed to integrate signals rather then refining primary signal with a secondary one. Furthermore, the tool combines different types of evidence from multiple samples.</p></sec><sec id="S8"><title>Detection of Mobile Elements</title><p>Mobile elements are repetitive DNA sequences that can change position within the genome (Lander et al., <xref rid="B51" ref-type="bibr">2001</xref>). Due to this intrinsic characteristic, their detection is challenging. Latest estimates suggest that more than half of the human genome is repetitive or repeat-derived (de Koning et al., <xref rid="B18" ref-type="bibr">2011</xref>). Though the DC approach can be ascribed to RP and SR methods, “the mates of the anchoring reads are then mapped to a custom but configurable library of known active ME consensus sequences” (Thung et al., <xref rid="B104" ref-type="bibr">2014</xref>).</p><p>Among WGS tools, Tangram (Wu et al., <xref rid="B111" ref-type="bibr">2014</xref>), a tool developed using Mosaik (Lee et al., <xref rid="B57" ref-type="bibr">2014</xref>) alignments (though it may use alignments produced by other mappers), Next-Generation VariationHunter (Hormozdiari et al., <xref rid="B32" ref-type="bibr">2010</xref>), Tea (Lee et al., <xref rid="B55" ref-type="bibr">2012</xref>), RetroSeq eKeane:2013kq, and Mobster (Thung et al., <xref rid="B104" ref-type="bibr">2014</xref>) have been reported in the literature.</p></sec><sec id="S9"><title>Conclusion</title><p>Overall, all the approaches discussed are fairly limited with respect to repeated regions of the reference genome (Alkan et al., <xref rid="B5" ref-type="bibr">2009</xref>, <xref rid="B4" ref-type="bibr">2011b</xref>). The complete range of structural DNA variation cannot be investigated with a single tool (Mills et al., <xref rid="B73" ref-type="bibr">2011</xref>), though combined methods may aid the discovery of SV. Three pipelines integrating different tools exploiting WGS data have been reported in the literature (Wong et al., <xref rid="B110" ref-type="bibr">2010</xref>; Lam et al., <xref rid="B50" ref-type="bibr">2012</xref>; Mimori et al., <xref rid="B74" ref-type="bibr">2013</xref>). WES data can be exploited for the investigation of SVs by means of RC, SR, and RP methods – though with limitations due to the intrinsic sparseness of exomic data.</p><p>Each method for the detection of SVs shows advantages/drawback. RC methods are particularly well-suited for the investigation of a particular class of SV, namely CNV. Notably, RC can be used to predict absolute copy number. A major drawback of RC tools is the poor breakpoint resolution. Furthermore, they cannot distinguish tandem from interspersed duplications. SR algorithms can accurately predict SV breakpoint (down to single-base resolution) as well as AS methods. Finally, the RP and SR approaches can be applied for the investigation of the widest range of SV classes (i.e., deletions, inversions, novel sequence insertions, tandem duplications), though both cannot be exploited for the calculation of absolute copy number.</p><p>The advent of third-generation sequencing (TGS) technology may contribute to overcome these issues (Schadt et al., <xref rid="B92" ref-type="bibr">2010</xref>; Niedringhaus et al., <xref rid="B77" ref-type="bibr">2011</xref>; Pareek et al., <xref rid="B83" ref-type="bibr">2011</xref>; Venkatesan and Bashir, <xref rid="B106" ref-type="bibr">2011</xref>). TGS single-end reads, characterized by read length up to thousands base pairs, may boost AS methods and the application of mapping algorithms allowing for split alignment such as BWA (Li and Durbin, <xref rid="B58" ref-type="bibr">2010</xref>), LAST (Kiełbasa et al., <xref rid="B44" ref-type="bibr">2011</xref>) and BLASR (Chaisson and Tesler, <xref rid="B13" ref-type="bibr">2012</xref>). Though TGS platforms rely on different chemistry, reads produced by platforms, such as PacBio RS (Kim et al., <xref rid="B45" ref-type="bibr">2014</xref>) and Oxford Nanopore MinION (Bayley, <xref rid="B9" ref-type="bibr">2015</xref>), show similar read length and base-calling accuracy (~85%) (Quail et al., <xref rid="B86" ref-type="bibr">2012</xref>; Quick et al., <xref rid="B87" ref-type="bibr">2014</xref>; Ashton et al., <xref rid="B7" ref-type="bibr">2015</xref>; Chaisson et al., <xref rid="B14" ref-type="bibr">2015</xref>). Recent works have demonstrated that these technologies allow for the investigation of complex repetitive regions of the human genome (Chaisson et al., <xref rid="B14" ref-type="bibr">2015</xref>) as well as the structure of complex antibiotic resistance islands in <italic>Salmonella typhi</italic> (Ashton et al., <xref rid="B7" ref-type="bibr">2015</xref>) and tandem repeats in human bacterial artificial chromosome (Jain et al., <xref rid="B37" ref-type="bibr">2015</xref>).</p></sec><sec id="S10"><title>Conflict of Interest Statement</title><p>The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.</p></sec></body><back><fn-group><fn id="fn1"><p><sup>1</sup><uri xlink:type="simple" xlink:href="http://www.ebi.ac.uk/dgva">http://www.ebi.ac.uk/dgva</uri></p></fn><fn id="fn2"><p><sup>2</sup><uri xlink:type="simple" xlink:href="http://www.ncbi.nlm.nih.gov/dbvar">http://www.ncbi.nlm.nih.gov/dbvar</uri></p></fn><fn id="fn3"><p><sup>3</sup><uri xlink:type="simple" xlink:href="http://www.omim.org">http://www.omim.org</uri></p></fn></fn-group><ref-list><title>References</title><ref id="B1"><mixed-citation publication-type="journal"><collab>1000 Genomes Project Consortium</collab><person-group person-group-type="author"><name><surname>Abecasis</surname><given-names>G. R.</given-names></name><name><surname>Altshuler</surname><given-names>D.</given-names></name><name><surname>Auton</surname><given-names>A.</given-names></name><name><surname>Brooks</surname><given-names>L. D.</given-names></name><name><surname>Durbin</surname><given-names>R. M.</given-names></name><etal></etal></person-group> (<year>2010</year>). <article-title>A map of human genome variation from population-scale sequencing</article-title>. <source>Nature</source><volume>467</volume>, <fpage>1061</fpage>–<lpage>1073</lpage>.<pub-id pub-id-type="doi">10.1038/nature09534</pub-id><pub-id pub-id-type="pmid">20981092</pub-id></mixed-citation></ref><ref id="B2"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Abyzov</surname><given-names>A.</given-names></name><name><surname>Urban</surname><given-names>A. E.</given-names></name><name><surname>Snyder</surname><given-names>M.</given-names></name><name><surname>Gerstein</surname><given-names>M.</given-names></name></person-group> (<year>2011</year>). <article-title>Cnvnator: an approach to discover, genotype, and characterize typical and atypical cnvs from family and population genome sequencing</article-title>. <source>Genome Res.</source><volume>21</volume>, <fpage>974</fpage>–<lpage>984</lpage>.<pub-id pub-id-type="doi">10.1101/gr.114876.110</pub-id><pub-id pub-id-type="pmid">21324876</pub-id></mixed-citation></ref><ref id="B3"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Alkan</surname><given-names>C.</given-names></name><name><surname>Coe</surname><given-names>B. P.</given-names></name><name><surname>Eichler</surname><given-names>E. E.</given-names></name></person-group> (<year>2011a</year>). <article-title>Genome structural variation discovery and genotyping</article-title>. <source>Nat. Rev. Genet.</source><volume>12</volume>, <fpage>363</fpage>–<lpage>376</lpage>.<pub-id pub-id-type="doi">10.1038/nrg2958</pub-id><pub-id pub-id-type="pmid">21358748</pub-id></mixed-citation></ref><ref id="B4"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Alkan</surname><given-names>C.</given-names></name><name><surname>Sajjadian</surname><given-names>S.</given-names></name><name><surname>Eichler</surname><given-names>E. E.</given-names></name></person-group> (<year>2011b</year>). <article-title>Limitations of next-generation genome sequence assembly</article-title>. <source>Nat. Methods</source><volume>8</volume>, <fpage>61</fpage>–<lpage>65</lpage>.<pub-id pub-id-type="doi">10.1038/nmeth.1527</pub-id><pub-id pub-id-type="pmid">21102452</pub-id></mixed-citation></ref><ref id="B5"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Alkan</surname><given-names>C.</given-names></name><name><surname>Kidd</surname><given-names>J. M.</given-names></name><name><surname>Marques-Bonet</surname><given-names>T.</given-names></name><name><surname>Aksay</surname><given-names>G.</given-names></name><name><surname>Antonacci</surname><given-names>F.</given-names></name><name><surname>Hormozdiari</surname><given-names>F.</given-names></name><etal></etal></person-group> (<year>2009</year>). <article-title>Personalized copy number and segmental duplication maps using next-generation sequencing</article-title>. <source>Nat. Genet.</source><volume>41</volume>, <fpage>1061</fpage>–<lpage>1067</lpage>.<pub-id pub-id-type="doi">10.1038/ng.437</pub-id><pub-id pub-id-type="pmid">19718026</pub-id></mixed-citation></ref><ref id="B6"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Alkodsi</surname><given-names>A.</given-names></name><name><surname>Louhimo</surname><given-names>R.</given-names></name><name><surname>Hautaniemi</surname><given-names>S.</given-names></name></person-group> (<year>2015</year>). <article-title>Comparative analysis of methods for identifying somatic copy number alterations from deep sequencing data</article-title>. <source>Brief. Bioinform.</source><volume>16</volume>, <fpage>242</fpage>–<lpage>254</lpage>.<pub-id pub-id-type="doi">10.1093/bib/bbu004</pub-id><pub-id pub-id-type="pmid">24599115</pub-id></mixed-citation></ref><ref id="B7"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ashton</surname><given-names>P. M.</given-names></name><name><surname>Nair</surname><given-names>S.</given-names></name><name><surname>Dallman</surname><given-names>T.</given-names></name><name><surname>Rubino</surname><given-names>S.</given-names></name><name><surname>Rabsch</surname><given-names>W.</given-names></name><name><surname>Mwaigwisya</surname><given-names>S.</given-names></name><etal></etal></person-group> (<year>2015</year>). <article-title>MinION nanopore sequencing identifies the position and structure of a bacterial antibiotic resistance island</article-title>. <source>Nat. Biotechnol.</source><volume>33</volume>, <fpage>296</fpage>–<lpage>300</lpage>.<pub-id pub-id-type="doi">10.1038/nbt.3103</pub-id><pub-id pub-id-type="pmid">25485618</pub-id></mixed-citation></ref><ref id="B8"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bansal</surname><given-names>V.</given-names></name><name><surname>Dorn</surname><given-names>C.</given-names></name><name><surname>Grunert</surname><given-names>M.</given-names></name><name><surname>Klaassen</surname><given-names>S.</given-names></name><name><surname>Hetzer</surname><given-names>R.</given-names></name><name><surname>Berger</surname><given-names>F.</given-names></name><etal></etal></person-group> (<year>2014</year>). <article-title>Outlier-based identification of copy number variations using targeted resequencing in a small cohort of patients with tetralogy of fallot</article-title>. <source>PLoS ONE</source><volume>9</volume>:<fpage>e85375</fpage>.<pub-id pub-id-type="doi">10.1371/journal.pone.0085375</pub-id><pub-id pub-id-type="pmid">24400131</pub-id></mixed-citation></ref><ref id="B9"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bayley</surname><given-names>H.</given-names></name></person-group> (<year>2015</year>). <article-title>Nanopore sequencing: from imagination to reality</article-title>. <source>Clin. Chem.</source><volume>61</volume>, <fpage>25</fpage>–<lpage>31</lpage>.<pub-id pub-id-type="doi">10.1373/clinchem.2014.223016</pub-id><pub-id pub-id-type="pmid">25477535</pub-id></mixed-citation></ref><ref id="B10"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Beadling</surname><given-names>C.</given-names></name><name><surname>Neff</surname><given-names>T. L.</given-names></name><name><surname>Heinrich</surname><given-names>M. C.</given-names></name><name><surname>Rhodes</surname><given-names>K.</given-names></name><name><surname>Thornton</surname><given-names>M.</given-names></name><name><surname>Leamon</surname><given-names>J.</given-names></name><etal></etal></person-group> (<year>2013</year>). <article-title>Combining highly multiplexed pcr with semiconductor-based sequencing for rapid cancer genotyping</article-title>. <source>J. Mol. Diagn.</source><volume>15</volume>, <fpage>171</fpage>–<lpage>176</lpage>.<pub-id pub-id-type="doi">10.1016/j.jmoldx.2012.09.003</pub-id><pub-id pub-id-type="pmid">23274167</pub-id></mixed-citation></ref><ref id="B11"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Boeva</surname><given-names>V.</given-names></name><name><surname>Popova</surname><given-names>T.</given-names></name><name><surname>Lienard</surname><given-names>M.</given-names></name><name><surname>Toffoli</surname><given-names>S.</given-names></name><name><surname>Kamal</surname><given-names>M.</given-names></name><name><surname>Le Tourneau</surname><given-names>C.</given-names></name><etal></etal></person-group> (<year>2014</year>). <article-title>Multi-factor data normalization enables the detection of copy number aberrations in amplicon sequencing data</article-title>. <source>Bioinformatics</source><volume>30</volume>, <fpage>3443</fpage>–<lpage>3450</lpage>.<pub-id pub-id-type="doi">10.1093/bioinformatics/btu436</pub-id><pub-id pub-id-type="pmid">25016581</pub-id></mixed-citation></ref><ref id="B12"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Campbell</surname><given-names>P. J.</given-names></name><name><surname>Stephens</surname><given-names>P. J.</given-names></name><name><surname>Pleasance</surname><given-names>E. D.</given-names></name><name><surname>O’Meara</surname><given-names>S.</given-names></name><name><surname>Li</surname><given-names>H.</given-names></name><name><surname>Santarius</surname><given-names>T.</given-names></name><etal></etal></person-group> (<year>2008</year>). <article-title>Identification of somatically acquired rearrangements in cancer using genome-wide massively parallel paired-end sequencing</article-title>. <source>Nat. Genet.</source><volume>40</volume>, <fpage>722</fpage>–<lpage>729</lpage>.<pub-id pub-id-type="doi">10.1038/ng.128</pub-id><pub-id pub-id-type="pmid">18438408</pub-id></mixed-citation></ref><ref id="B13"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Chaisson</surname><given-names>M. J.</given-names></name><name><surname>Tesler</surname><given-names>G.</given-names></name></person-group> (<year>2012</year>). <article-title>Mapping single molecule sequencing reads using basic local alignment with successive refinement (blasr): application and theory</article-title>. <source>BMC Bioinformatics</source><volume>13</volume>:<fpage>238</fpage>.<pub-id pub-id-type="doi">10.1186/1471-2105-13-238</pub-id><pub-id pub-id-type="pmid">22988817</pub-id></mixed-citation></ref><ref id="B14"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Chaisson</surname><given-names>M. J. P.</given-names></name><name><surname>Huddleston</surname><given-names>J.</given-names></name><name><surname>Dennis</surname><given-names>M. Y.</given-names></name><name><surname>Sudmant</surname><given-names>P. H.</given-names></name><name><surname>Malig</surname><given-names>M.</given-names></name><name><surname>Hormozdiari</surname><given-names>F.</given-names></name><etal></etal></person-group> (<year>2015</year>). <article-title>Resolving the complexity of the human genome using single-molecule sequencing</article-title>. <source>Nature</source><volume>517</volume>, <fpage>608</fpage>–<lpage>611</lpage>.<pub-id pub-id-type="doi">10.1038/nature13907</pub-id><pub-id pub-id-type="pmid">25383537</pub-id></mixed-citation></ref><ref id="B15"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Chen</surname><given-names>K.</given-names></name><name><surname>Wallis</surname><given-names>J. W.</given-names></name><name><surname>McLellan</surname><given-names>M. D.</given-names></name><name><surname>Larson</surname><given-names>D. E.</given-names></name><name><surname>Kalicki</surname><given-names>J. M.</given-names></name><name><surname>Pohl</surname><given-names>C. S.</given-names></name><etal></etal></person-group> (<year>2009</year>). <article-title>Breakdancer: an algorithm for high-resolution mapping of genomic structural variation</article-title>. <source>Nat. Methods</source><volume>6</volume>, <fpage>677</fpage>–<lpage>681</lpage>.<pub-id pub-id-type="doi">10.1038/nmeth.1363</pub-id><pub-id pub-id-type="pmid">19668202</pub-id></mixed-citation></ref><ref id="B16"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Chiang</surname><given-names>D. Y.</given-names></name><name><surname>Getz</surname><given-names>G.</given-names></name><name><surname>Jaffe</surname><given-names>D. B.</given-names></name><name><surname>O’Kelly</surname><given-names>M. J. T.</given-names></name><name><surname>Zhao</surname><given-names>X.</given-names></name><name><surname>Carter</surname><given-names>S. L.</given-names></name><etal></etal></person-group> (<year>2009</year>). <article-title>High-resolution mapping of copy-number alterations with massively parallel sequencing</article-title>. <source>Nat. Methods</source><volume>6</volume>, <fpage>99</fpage>–<lpage>103</lpage>.<pub-id pub-id-type="doi">10.1038/nmeth.1276</pub-id><pub-id pub-id-type="pmid">19043412</pub-id></mixed-citation></ref><ref id="B17"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Conrad</surname><given-names>D. F.</given-names></name><name><surname>Pinto</surname><given-names>D.</given-names></name><name><surname>Redon</surname><given-names>R.</given-names></name><name><surname>Feuk</surname><given-names>L.</given-names></name><name><surname>Gokcumen</surname><given-names>O.</given-names></name><name><surname>Zhang</surname><given-names>Y.</given-names></name><etal></etal></person-group> (<year>2010</year>). <article-title>Origins and functional impact of copy number variation in the human genome</article-title>. <source>Nature</source><volume>464</volume>, <fpage>704</fpage>–<lpage>712</lpage>.<pub-id pub-id-type="doi">10.1038/nature08516</pub-id><pub-id pub-id-type="pmid">19812545</pub-id></mixed-citation></ref><ref id="B18"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>de Koning</surname><given-names>A. P. J.</given-names></name><name><surname>Gu</surname><given-names>W.</given-names></name><name><surname>Castoe</surname><given-names>T. A.</given-names></name><name><surname>Batzer</surname><given-names>M. A.</given-names></name><name><surname>Pollock</surname><given-names>D. D.</given-names></name></person-group> (<year>2011</year>). <article-title>Repetitive elements may comprise over two-thirds of the human genome</article-title>. <source>PLoS Genet.</source><volume>7</volume>:<fpage>e1002384</fpage>.<pub-id pub-id-type="doi">10.1371/journal.pgen.1002384</pub-id><pub-id pub-id-type="pmid">22144907</pub-id></mixed-citation></ref><ref id="B19"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Desai</surname><given-names>A. N.</given-names></name><name><surname>Jere</surname><given-names>A.</given-names></name></person-group> (<year>2012</year>). <article-title>Next-generation sequencing: ready for the clinics?</article-title><source>Clin. Genet.</source><volume>81</volume>, <fpage>503</fpage>–<lpage>510</lpage>.<pub-id pub-id-type="doi">10.1111/j.1399-0004.2012.01865.x</pub-id><pub-id pub-id-type="pmid">22375550</pub-id></mixed-citation></ref><ref id="B20"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Duan</surname><given-names>J.</given-names></name><name><surname>Zhang</surname><given-names>J.-G.</given-names></name><name><surname>Deng</surname><given-names>H.-W.</given-names></name><name><surname>Wang</surname><given-names>Y.-P.</given-names></name></person-group> (<year>2013</year>). <article-title>Comparative studies of copy number variation detection methods for next-generation sequencing technologies</article-title>. <source>PLoS ONE</source><volume>8</volume>:<fpage>e59128</fpage>.<pub-id pub-id-type="doi">10.1371/journal.pone.0059128</pub-id><pub-id pub-id-type="pmid">23527109</pub-id></mixed-citation></ref><ref id="B21"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Earl</surname><given-names>D.</given-names></name><name><surname>Bradnam</surname><given-names>K.</given-names></name><name><surname>St John</surname><given-names>J.</given-names></name><name><surname>Darling</surname><given-names>A.</given-names></name><name><surname>Lin</surname><given-names>D.</given-names></name><name><surname>Fass</surname><given-names>J.</given-names></name><etal></etal></person-group> (<year>2011</year>). <article-title>Assemblathon 1: a competitive assessment of de novo short read assembly methods</article-title>. <source>Genome Res.</source><volume>21</volume>, <fpage>2224</fpage>–<lpage>2241</lpage>.<pub-id pub-id-type="doi">10.1101/gr.126599.111</pub-id><pub-id pub-id-type="pmid">21926179</pub-id></mixed-citation></ref><ref id="B22"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Fromer</surname><given-names>M.</given-names></name><name><surname>Moran</surname><given-names>J. L.</given-names></name><name><surname>Chambert</surname><given-names>K.</given-names></name><name><surname>Banks</surname><given-names>E.</given-names></name><name><surname>Bergen</surname><given-names>S. E.</given-names></name><name><surname>Ruderfer</surname><given-names>D. M.</given-names></name><etal></etal></person-group> (<year>2012</year>). <article-title>Discovery and statistical genotyping of copy-number variation from whole-exome sequencing depth</article-title>. <source>Am. J. Hum. Genet.</source><volume>91</volume>, <fpage>597</fpage>–<lpage>607</lpage>.<pub-id pub-id-type="doi">10.1016/j.ajhg.2012.08.005</pub-id><pub-id pub-id-type="pmid">23040492</pub-id></mixed-citation></ref><ref id="B23"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Girirajan</surname><given-names>S.</given-names></name><name><surname>Dennis</surname><given-names>M. Y.</given-names></name><name><surname>Baker</surname><given-names>C.</given-names></name><name><surname>Malig</surname><given-names>M.</given-names></name><name><surname>Coe</surname><given-names>B. P.</given-names></name><name><surname>Campbell</surname><given-names>C. D.</given-names></name><etal></etal></person-group> (<year>2013</year>). <article-title>Refinement and discovery of new hotspots of copy-number variation associated with autism spectrum disorder</article-title>. <source>Am. J. Hum. Genet.</source><volume>92</volume>, <fpage>221</fpage>–<lpage>237</lpage>.<pub-id pub-id-type="doi">10.1016/j.ajhg.2012.12.016</pub-id><pub-id pub-id-type="pmid">23375656</pub-id></mixed-citation></ref><ref id="B24"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Gnerre</surname><given-names>S.</given-names></name><name><surname>Maccallum</surname><given-names>I.</given-names></name><name><surname>Przybylski</surname><given-names>D.</given-names></name><name><surname>Ribeiro</surname><given-names>F. J.</given-names></name><name><surname>Burton</surname><given-names>J. N.</given-names></name><name><surname>Walker</surname><given-names>B. J.</given-names></name><etal></etal></person-group> (<year>2011</year>). <article-title>High-quality draft assemblies of mammalian genomes from massively parallel sequence data</article-title>. <source>Proc. Natl. Acad. Sci. U.S.A.</source><volume>108</volume>, <fpage>1513</fpage>–<lpage>1518</lpage>.<pub-id pub-id-type="doi">10.1073/pnas.1017351108</pub-id><pub-id pub-id-type="pmid">21187386</pub-id></mixed-citation></ref><ref id="B25"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Gusnanto</surname><given-names>A.</given-names></name><name><surname>Wood</surname><given-names>H. M.</given-names></name><name><surname>Pawitan</surname><given-names>Y.</given-names></name><name><surname>Rabbitts</surname><given-names>P.</given-names></name><name><surname>Berri</surname><given-names>S.</given-names></name></person-group> (<year>2012</year>). <article-title>Correcting for cancer genome size and tumour cell content enables better estimation of copy number alterations from next-generation sequence data</article-title>. <source>Bioinformatics</source><volume>28</volume>, <fpage>40</fpage>–<lpage>47</lpage>.<pub-id pub-id-type="doi">10.1093/bioinformatics/btr593</pub-id><pub-id pub-id-type="pmid">22039209</pub-id></mixed-citation></ref><ref id="B26"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hach</surname><given-names>F.</given-names></name><name><surname>Hormozdiari</surname><given-names>F.</given-names></name><name><surname>Alkan</surname><given-names>C.</given-names></name><name><surname>Hormozdiari</surname><given-names>F.</given-names></name><name><surname>Birol</surname><given-names>I.</given-names></name><name><surname>Eichler</surname><given-names>E. E.</given-names></name><etal></etal></person-group> (<year>2010</year>). <article-title>mrsfast: a cache-oblivious algorithm for short-read mapping</article-title>. <source>Nat. Methods</source><volume>7</volume>, <fpage>576</fpage>–<lpage>577</lpage>.<pub-id pub-id-type="doi">10.1038/nmeth0810-576</pub-id><pub-id pub-id-type="pmid">20676076</pub-id></mixed-citation></ref><ref id="B27"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hajirasouliha</surname><given-names>I.</given-names></name><name><surname>Hormozdiari</surname><given-names>F.</given-names></name><name><surname>Alkan</surname><given-names>C.</given-names></name><name><surname>Kidd</surname><given-names>J. M.</given-names></name><name><surname>Birol</surname><given-names>I.</given-names></name><name><surname>Eichler</surname><given-names>E. E.</given-names></name><etal></etal></person-group> (<year>2010</year>). <article-title>Detection and characterization of novel sequence insertions using paired-end next-generation sequencing</article-title>. <source>Bioinformatics</source><volume>26</volume>, <fpage>1277</fpage>–<lpage>1283</lpage>.<pub-id pub-id-type="doi">10.1093/bioinformatics/btq152</pub-id><pub-id pub-id-type="pmid">20385726</pub-id></mixed-citation></ref><ref id="B28"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Handsaker</surname><given-names>R. E.</given-names></name><name><surname>Korn</surname><given-names>J. M.</given-names></name><name><surname>Nemesh</surname><given-names>J.</given-names></name><name><surname>McCarroll</surname><given-names>S. A.</given-names></name></person-group> (<year>2011</year>). <article-title>Discovery and genotyping of genome structural polymorphism by sequencing on a population scale</article-title>. <source>Nat. Genet.</source><volume>43</volume>, <fpage>269</fpage>–<lpage>276</lpage>.<pub-id pub-id-type="doi">10.1038/ng.768</pub-id><pub-id pub-id-type="pmid">21317889</pub-id></mixed-citation></ref><ref id="B29"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Harismendy</surname><given-names>O.</given-names></name><name><surname>Ng</surname><given-names>P. C.</given-names></name><name><surname>Strausberg</surname><given-names>R. L.</given-names></name><name><surname>Wang</surname><given-names>X.</given-names></name><name><surname>Stockwell</surname><given-names>T. B.</given-names></name><name><surname>Beeson</surname><given-names>K. Y.</given-names></name><etal></etal></person-group> (<year>2009</year>). <article-title>Evaluation of next generation sequencing platforms for population targeted sequencing studies</article-title>. <source>Genome Biol.</source><volume>10</volume>, <fpage>R32</fpage>.<pub-id pub-id-type="doi">10.1186/gb-2009-10-3-r32</pub-id><pub-id pub-id-type="pmid">19327155</pub-id></mixed-citation></ref><ref id="B30"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hart</surname><given-names>S. N.</given-names></name><name><surname>Sarangi</surname><given-names>V.</given-names></name><name><surname>Moore</surname><given-names>R.</given-names></name><name><surname>Baheti</surname><given-names>S.</given-names></name><name><surname>Bhavsar</surname><given-names>J. D.</given-names></name><name><surname>Couch</surname><given-names>F. J.</given-names></name><etal></etal></person-group> (<year>2013</year>). <article-title>Softsearch: integration of multiple sequence features to identify breakpoints of structural variations</article-title>. <source>PLoS ONE</source><volume>8</volume>:<fpage>e83356</fpage>.<pub-id pub-id-type="doi">10.1371/journal.pone.0083356</pub-id><pub-id pub-id-type="pmid">24358278</pub-id></mixed-citation></ref><ref id="B31"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hormozdiari</surname><given-names>F.</given-names></name><name><surname>Alkan</surname><given-names>C.</given-names></name><name><surname>Eichler</surname><given-names>E. E.</given-names></name><name><surname>Sahinalp</surname><given-names>S. C.</given-names></name></person-group> (<year>2009</year>). <article-title>Combinatorial algorithms for structural variation detection in high-throughput sequenced genomes</article-title>. <source>Genome Res.</source><volume>19</volume>, <fpage>1270</fpage>–<lpage>1278</lpage>.<pub-id pub-id-type="doi">10.1101/gr.088633.108</pub-id><pub-id pub-id-type="pmid">19447966</pub-id></mixed-citation></ref><ref id="B32"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hormozdiari</surname><given-names>F.</given-names></name><name><surname>Hajirasouliha</surname><given-names>I.</given-names></name><name><surname>Dao</surname><given-names>P.</given-names></name><name><surname>Hach</surname><given-names>F.</given-names></name><name><surname>Yorukoglu</surname><given-names>D.</given-names></name><name><surname>Alkan</surname><given-names>C.</given-names></name><etal></etal></person-group> (<year>2010</year>). <article-title>Next-generation variationhunter: combinatorial algorithms for transposon insertion discovery</article-title>. <source>Bioinformatics</source><volume>26</volume>, <fpage>i350</fpage>–<lpage>i357</lpage>.<pub-id pub-id-type="doi">10.1093/bioinformatics/btq216</pub-id><pub-id pub-id-type="pmid">20529927</pub-id></mixed-citation></ref><ref id="B33"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hormozdiari</surname><given-names>F.</given-names></name><name><surname>Hajirasouliha</surname><given-names>I.</given-names></name><name><surname>McPherson</surname><given-names>A.</given-names></name><name><surname>Eichler</surname><given-names>E. E.</given-names></name><name><surname>Sahinalp</surname><given-names>S. C.</given-names></name></person-group> (<year>2011</year>). <article-title>Simultaneous structural variation discovery among multiple paired-end sequenced genomes</article-title>. <source>Genome Res.</source><volume>21</volume>, <fpage>2203</fpage>–<lpage>2212</lpage>.<pub-id pub-id-type="doi">10.1101/gr.120501.111</pub-id><pub-id pub-id-type="pmid">22048523</pub-id></mixed-citation></ref><ref id="B34"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Iafrate</surname><given-names>A. J.</given-names></name><name><surname>Feuk</surname><given-names>L.</given-names></name><name><surname>Rivera</surname><given-names>M. N.</given-names></name><name><surname>Listewnik</surname><given-names>M. L.</given-names></name><name><surname>Donahoe</surname><given-names>P. K.</given-names></name><name><surname>Qi</surname><given-names>Y.</given-names></name><etal></etal></person-group> (<year>2004</year>). <article-title>Detection of large-scale variation in the human genome</article-title>. <source>Nat. Genet.</source><volume>36</volume>, <fpage>949</fpage>–<lpage>951</lpage>.<pub-id pub-id-type="doi">10.1038/ng1416</pub-id><pub-id pub-id-type="pmid">15286789</pub-id></mixed-citation></ref><ref id="B35"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Iqbal</surname><given-names>Z.</given-names></name><name><surname>Caccamo</surname><given-names>M.</given-names></name><name><surname>Turner</surname><given-names>I.</given-names></name><name><surname>Flicek</surname><given-names>P.</given-names></name><name><surname>McVean</surname><given-names>G.</given-names></name></person-group> (<year>2012</year>). <article-title>De novo assembly and genotyping of variants using colored de bruijn graphs</article-title>. <source>Nat. Genet.</source><volume>44</volume>, <fpage>226</fpage>–<lpage>232</lpage>.<pub-id pub-id-type="doi">10.1038/ng.1028</pub-id><pub-id pub-id-type="pmid">22231483</pub-id></mixed-citation></ref><ref id="B36"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ivakhno</surname><given-names>S.</given-names></name><name><surname>Royce</surname><given-names>T.</given-names></name><name><surname>Cox</surname><given-names>A. J.</given-names></name><name><surname>Evers</surname><given-names>D. J.</given-names></name><name><surname>Cheetham</surname><given-names>R. K.</given-names></name><name><surname>Tavaré</surname><given-names>S.</given-names></name></person-group> (<year>2010</year>). <article-title>Cnaseg – a novel framework for identification of copy number changes in cancer from second-generation sequencing data</article-title>. <source>Bioinformatics</source><volume>26</volume>, <fpage>3051</fpage>–<lpage>3058</lpage>.<pub-id pub-id-type="doi">10.1093/bioinformatics/btq587</pub-id><pub-id pub-id-type="pmid">20966003</pub-id></mixed-citation></ref><ref id="B37"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Jain</surname><given-names>M.</given-names></name><name><surname>Fiddes</surname><given-names>I. T.</given-names></name><name><surname>Miga</surname><given-names>K. H.</given-names></name><name><surname>Olsen</surname><given-names>H. E.</given-names></name><name><surname>Paten</surname><given-names>B.</given-names></name><name><surname>Akeson</surname><given-names>M.</given-names></name></person-group> (<year>2015</year>). <article-title>Improved data analysis for the minion nanopore sequencer</article-title>. <source>Nat. Methods</source><volume>12</volume>, <fpage>351</fpage>–<lpage>356</lpage>.<pub-id pub-id-type="doi">10.1038/nmeth.3290</pub-id><pub-id pub-id-type="pmid">25686389</pub-id></mixed-citation></ref><ref id="B38"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Jiang</surname><given-names>Y.</given-names></name><name><surname>Oldridge</surname><given-names>D. A.</given-names></name><name><surname>Diskin</surname><given-names>S. J.</given-names></name><name><surname>Zhang</surname><given-names>N. R.</given-names></name></person-group> (<year>2015</year>). <article-title>Codex: a normalization and copy number variation detection method for whole exome sequencing</article-title>. <source>Nucleic Acids Res.</source><volume>43</volume>, <fpage>e39</fpage>.<pub-id pub-id-type="doi">10.1093/nar/gku1363</pub-id><pub-id pub-id-type="pmid">25618849</pub-id></mixed-citation></ref><ref id="B39"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Jiang</surname><given-names>Y.</given-names></name><name><surname>Wang</surname><given-names>Y.</given-names></name><name><surname>Brudno</surname><given-names>M.</given-names></name></person-group> (<year>2012</year>). <article-title>Prism: pair-read informed split-read mapping for base-pair level detection of insertion, deletion and structural variants</article-title>. <source>Bioinformatics</source><volume>28</volume>, <fpage>2576</fpage>–<lpage>2583</lpage>.<pub-id pub-id-type="doi">10.1093/bioinformatics/bts484</pub-id><pub-id pub-id-type="pmid">22851530</pub-id></mixed-citation></ref><ref id="B40"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kadalayil</surname><given-names>L.</given-names></name><name><surname>Rafiq</surname><given-names>S.</given-names></name><name><surname>Rose-Zerilli</surname><given-names>M. J. J.</given-names></name><name><surname>Pengelly</surname><given-names>R. J.</given-names></name><name><surname>Parker</surname><given-names>H.</given-names></name><name><surname>Oscier</surname><given-names>D.</given-names></name><etal></etal></person-group> (<year>2015</year>). <article-title>Exome sequence read depth methods for identifying copy number changes</article-title>. <source>Brief. Bioinform.</source><volume>16</volume>, <fpage>380</fpage>–<lpage>392</lpage>.<pub-id pub-id-type="doi">10.1093/bib/bbu027</pub-id><pub-id pub-id-type="pmid">25169955</pub-id></mixed-citation></ref><ref id="B41"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Karakoc</surname><given-names>E.</given-names></name><name><surname>Alkan</surname><given-names>C.</given-names></name><name><surname>O’Roak</surname><given-names>B. J.</given-names></name><name><surname>Dennis</surname><given-names>M. Y.</given-names></name><name><surname>Vives</surname><given-names>L.</given-names></name><name><surname>Mark</surname><given-names>K.</given-names></name><etal></etal></person-group> (<year>2012</year>). <article-title>Detection of structural variants and indels within exome data</article-title>. <source>Nat. Methods</source><volume>9</volume>, <fpage>176</fpage>–<lpage>178</lpage>.<pub-id pub-id-type="doi">10.1038/nmeth.1810</pub-id><pub-id pub-id-type="pmid">22179552</pub-id></mixed-citation></ref><ref id="B42"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Keane</surname><given-names>T. M.</given-names></name><name><surname>Wong</surname><given-names>K.</given-names></name><name><surname>Adams</surname><given-names>D. J.</given-names></name></person-group> (<year>2013</year>). <article-title>Retroseq: transposable element discovery from next-generation sequencing data</article-title>. <source>Bioinformatics</source><volume>29</volume>, <fpage>389</fpage>–<lpage>390</lpage>.<pub-id pub-id-type="doi">10.1093/bioinformatics/bts697</pub-id><pub-id pub-id-type="pmid">23233656</pub-id></mixed-citation></ref><ref id="B43"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kelley</surname><given-names>D. R.</given-names></name><name><surname>Schatz</surname><given-names>M. C.</given-names></name><name><surname>Salzberg</surname><given-names>S. L.</given-names></name></person-group> (<year>2010</year>). <article-title>Quake: quality-aware detection and correction of sequencing errors</article-title>. <source>Genome Biol.</source><volume>11</volume>, <fpage>R116</fpage>.<pub-id pub-id-type="doi">10.1186/gb-2010-11-11-r116</pub-id><pub-id pub-id-type="pmid">21114842</pub-id></mixed-citation></ref><ref id="B44"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kiełbasa</surname><given-names>S. M.</given-names></name><name><surname>Wan</surname><given-names>R.</given-names></name><name><surname>Sato</surname><given-names>K.</given-names></name><name><surname>Horton</surname><given-names>P.</given-names></name><name><surname>Frith</surname><given-names>M. C.</given-names></name></person-group> (<year>2011</year>). <article-title>Adaptive seeds tame genomic sequence comparison</article-title>. <source>Genome Res.</source><volume>21</volume>, <fpage>487</fpage>–<lpage>493</lpage>.<pub-id pub-id-type="doi">10.1101/gr.113985.110</pub-id><pub-id pub-id-type="pmid">21209072</pub-id></mixed-citation></ref><ref id="B45"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kim</surname><given-names>K. E.</given-names></name><name><surname>Peluso</surname><given-names>P.</given-names></name><name><surname>Babayan</surname><given-names>P.</given-names></name><name><surname>Yeadon</surname><given-names>P. J.</given-names></name><name><surname>Yu</surname><given-names>C.</given-names></name><name><surname>Fisher</surname><given-names>W. W.</given-names></name><etal></etal></person-group> (<year>2014</year>). <article-title>Long-read, whole-genome shotgun sequence data for five model organisms</article-title>. <source>Sci. Data</source><volume>1</volume>, <fpage>140045</fpage>.<pub-id pub-id-type="doi">10.1038/sdata.2014.45</pub-id><pub-id pub-id-type="pmid">25977796</pub-id></mixed-citation></ref><ref id="B46"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kim</surname><given-names>T.-M.</given-names></name><name><surname>Luquette</surname><given-names>L. J.</given-names></name><name><surname>Xi</surname><given-names>R.</given-names></name><name><surname>Park</surname><given-names>P. J.</given-names></name></person-group> (<year>2010</year>). <article-title>rsw-seq: algorithm for detection of copy number alterations in deep sequencing data</article-title>. <source>BMC Bioinformatics</source><volume>11</volume>:<fpage>432</fpage>.<pub-id pub-id-type="doi">10.1186/1471-2105-11-432</pub-id><pub-id pub-id-type="pmid">20718989</pub-id></mixed-citation></ref><ref id="B47"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Klambauer</surname><given-names>G.</given-names></name><name><surname>Schwarzbauer</surname><given-names>K.</given-names></name><name><surname>Mayr</surname><given-names>A.</given-names></name><name><surname>Clevert</surname><given-names>D.-A.</given-names></name><name><surname>Mitterecker</surname><given-names>A.</given-names></name><name><surname>Bodenhofer</surname><given-names>U.</given-names></name><etal></etal></person-group> (<year>2012</year>). <article-title>cn.mops: mixture of poissons for discovering copy number variations in next-generation sequencing data with a low false discovery rate</article-title>. <source>Nucleic Acids Res.</source><volume>40</volume>, <fpage>e69</fpage>.<pub-id pub-id-type="doi">10.1093/nar/gks003</pub-id><pub-id pub-id-type="pmid">22302147</pub-id></mixed-citation></ref><ref id="B48"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Korbel</surname><given-names>J. O.</given-names></name><name><surname>Abyzov</surname><given-names>A.</given-names></name><name><surname>Mu</surname><given-names>X. J.</given-names></name><name><surname>Carriero</surname><given-names>N.</given-names></name><name><surname>Cayting</surname><given-names>P.</given-names></name><name><surname>Zhang</surname><given-names>Z.</given-names></name><etal></etal></person-group> (<year>2009</year>). <article-title>Pemer: a computational framework with simulation-based error models for inferring genomic structural variants from massive paired-end sequencing data</article-title>. <source>Genome Biol.</source><volume>10</volume>, <fpage>R23</fpage>.<pub-id pub-id-type="doi">10.1186/gb-2009-10-2-r23</pub-id><pub-id pub-id-type="pmid">19236709</pub-id></mixed-citation></ref><ref id="B49"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Krumm</surname><given-names>N.</given-names></name><name><surname>Sudmant</surname><given-names>P. H.</given-names></name><name><surname>Ko</surname><given-names>A.</given-names></name><name><surname>O’Roak</surname><given-names>B. J.</given-names></name><name><surname>Malig</surname><given-names>M.</given-names></name><name><surname>Coe</surname><given-names>B. P.</given-names></name><etal></etal></person-group> (<year>2012</year>). <article-title>Copy number variation detection and genotyping from exome sequence data</article-title>. <source>Genome Res.</source><volume>22</volume>, <fpage>1525</fpage>–<lpage>1532</lpage>.<pub-id pub-id-type="doi">10.1101/gr.138115.112</pub-id><pub-id pub-id-type="pmid">22585873</pub-id></mixed-citation></ref><ref id="B50"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lam</surname><given-names>H. Y. K.</given-names></name><name><surname>Pan</surname><given-names>C.</given-names></name><name><surname>Clark</surname><given-names>M. J.</given-names></name><name><surname>Lacroute</surname><given-names>P.</given-names></name><name><surname>Chen</surname><given-names>R.</given-names></name><name><surname>Haraksingh</surname><given-names>R.</given-names></name><etal></etal></person-group> (<year>2012</year>). <article-title>Detecting and annotating genetic variations using the hugeseq pipeline</article-title>. <source>Nat. Biotechnol.</source><volume>30</volume>, <fpage>226</fpage>–<lpage>229</lpage>.<pub-id pub-id-type="doi">10.1038/nbt.2134</pub-id><pub-id pub-id-type="pmid">22398614</pub-id></mixed-citation></ref><ref id="B51"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lander</surname><given-names>E. S.</given-names></name><name><surname>Linton</surname><given-names>L. M.</given-names></name><name><surname>Birren</surname><given-names>B.</given-names></name><name><surname>Nusbaum</surname><given-names>C.</given-names></name><name><surname>Zody</surname><given-names>M. C.</given-names></name><name><surname>Baldwin</surname><given-names>J.</given-names></name><etal></etal></person-group> (<year>2001</year>). <article-title>Initial sequencing and analysis of the human genome</article-title>. <source>Nature</source><volume>409</volume>, <fpage>860</fpage>–<lpage>921</lpage>.<pub-id pub-id-type="doi">10.1038/35057062</pub-id><pub-id pub-id-type="pmid">11237011</pub-id></mixed-citation></ref><ref id="B52"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Langmead</surname><given-names>B.</given-names></name><name><surname>Trapnell</surname><given-names>C.</given-names></name><name><surname>Pop</surname><given-names>M.</given-names></name><name><surname>Salzberg</surname><given-names>S. L.</given-names></name></person-group> (<year>2009</year>). <article-title>Ultrafast and memory-efficient alignment of short DNA sequences to the human genome</article-title>. <source>Genome Biol.</source><volume>10</volume>, <fpage>R25</fpage>.<pub-id pub-id-type="doi">10.1186/gb-2009-10-3-r25</pub-id><pub-id pub-id-type="pmid">19261174</pub-id></mixed-citation></ref><ref id="B53"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lappalainen</surname><given-names>I.</given-names></name><name><surname>Lopez</surname><given-names>J.</given-names></name><name><surname>Skipper</surname><given-names>L.</given-names></name><name><surname>Hefferon</surname><given-names>T.</given-names></name><name><surname>Spalding</surname><given-names>J. D.</given-names></name><name><surname>Garner</surname><given-names>J.</given-names></name><etal></etal></person-group> (<year>2013</year>). <article-title>Dbvar and dgva: public archives for genomic structural variation</article-title>. <source>Nucleic Acids Res.</source><volume>41</volume>, <fpage>D936</fpage>–<lpage>D941</lpage>.<pub-id pub-id-type="doi">10.1093/nar/gks1213</pub-id><pub-id pub-id-type="pmid">23193291</pub-id></mixed-citation></ref><ref id="B54"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Layer</surname><given-names>R. M.</given-names></name><name><surname>Chiang</surname><given-names>C.</given-names></name><name><surname>Quinlan</surname><given-names>A. R.</given-names></name><name><surname>Hall</surname><given-names>I. M.</given-names></name></person-group> (<year>2014</year>). <article-title>Lumpy: a probabilistic framework for structural variant discovery</article-title>. <source>Genome Biol.</source><volume>15</volume>, <fpage>R84</fpage>.<pub-id pub-id-type="doi">10.1186/gb-2014-15-6-r84</pub-id><pub-id pub-id-type="pmid">24970577</pub-id></mixed-citation></ref><ref id="B55"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lee</surname><given-names>E.</given-names></name><name><surname>Iskow</surname><given-names>R.</given-names></name><name><surname>Yang</surname><given-names>L.</given-names></name><name><surname>Gokcumen</surname><given-names>O.</given-names></name><name><surname>Haseley</surname><given-names>P.</given-names></name><name><surname>Luquette</surname><given-names>L. J.</given-names><suffix>III</suffix></name><etal></etal></person-group> (<year>2012</year>). <article-title>Landscape of somatic retrotransposition in human cancers</article-title>. <source>Science</source><volume>337</volume>, <fpage>967</fpage>–<lpage>971</lpage>.<pub-id pub-id-type="doi">10.1126/science.1222077</pub-id><pub-id pub-id-type="pmid">22745252</pub-id></mixed-citation></ref><ref id="B56"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lee</surname><given-names>S.</given-names></name><name><surname>Hormozdiari</surname><given-names>F.</given-names></name><name><surname>Alkan</surname><given-names>C.</given-names></name><name><surname>Brudno</surname><given-names>M.</given-names></name></person-group> (<year>2009</year>). <article-title>Modil: detecting small indels from clone-end sequencing with mixtures of distributions</article-title>. <source>Nat. Methods</source><volume>6</volume>, <fpage>473</fpage>–<lpage>474</lpage>.<pub-id pub-id-type="doi">10.1038/nmeth.f.256</pub-id><pub-id pub-id-type="pmid">19483690</pub-id></mixed-citation></ref><ref id="B57"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lee</surname><given-names>W.-P.</given-names></name><name><surname>Stromberg</surname><given-names>M. P.</given-names></name><name><surname>Ward</surname><given-names>A.</given-names></name><name><surname>Stewart</surname><given-names>C.</given-names></name><name><surname>Garrison</surname><given-names>E. P.</given-names></name><name><surname>Marth</surname><given-names>G. T.</given-names></name></person-group> (<year>2014</year>). <article-title>Mosaik: a hash-based algorithm for accurate next-generation sequencing short-read mapping</article-title>. <source>PLoS ONE</source><volume>9</volume>:<fpage>e90581</fpage>.<pub-id pub-id-type="doi">10.1371/journal.pone.0090581</pub-id><pub-id pub-id-type="pmid">24599324</pub-id></mixed-citation></ref><ref id="B58"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Li</surname><given-names>H.</given-names></name><name><surname>Durbin</surname><given-names>R.</given-names></name></person-group> (<year>2010</year>). <article-title>Fast and accurate long-read alignment with burrows-wheeler transform</article-title>. <source>Bioinformatics</source><volume>26</volume>, <fpage>589</fpage>–<lpage>595</lpage>.<pub-id pub-id-type="doi">10.1093/bioinformatics/btp698</pub-id><pub-id pub-id-type="pmid">20080505</pub-id></mixed-citation></ref><ref id="B59"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Li</surname><given-names>R.</given-names></name><name><surname>Fan</surname><given-names>W.</given-names></name><name><surname>Tian</surname><given-names>G.</given-names></name><name><surname>Zhu</surname><given-names>H.</given-names></name><name><surname>He</surname><given-names>L.</given-names></name><name><surname>Cai</surname><given-names>J.</given-names></name><etal></etal></person-group> (<year>2010</year>). <article-title>The sequence and de novo assembly of the giant panda genome</article-title>. <source>Nature</source><volume>463</volume>, <fpage>311</fpage>–<lpage>317</lpage>.<pub-id pub-id-type="doi">10.1038/nature08696</pub-id><pub-id pub-id-type="pmid">20010809</pub-id></mixed-citation></ref><ref id="B60"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Li</surname><given-names>X.</given-names></name><name><surname>Chen</surname><given-names>S.</given-names></name><name><surname>Xie</surname><given-names>W.</given-names></name><name><surname>Vogel</surname><given-names>I.</given-names></name><name><surname>Choy</surname><given-names>K. W.</given-names></name><name><surname>Chen</surname><given-names>F.</given-names></name><etal></etal></person-group> (<year>2014</year>). <article-title>Pscc: sensitive and reliable population-scale copy number variation detection method based on low coverage sequencing</article-title>. <source>PLoS ONE</source><volume>9</volume>:<fpage>e85096</fpage>.<pub-id pub-id-type="doi">10.1371/journal.pone.0085096</pub-id><pub-id pub-id-type="pmid">24465483</pub-id></mixed-citation></ref><ref id="B61"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lin</surname><given-names>K.</given-names></name><name><surname>Smit</surname><given-names>S.</given-names></name><name><surname>Bonnema</surname><given-names>G.</given-names></name><name><surname>Sanchez-Perez</surname><given-names>G.</given-names></name><name><surname>de Ridder</surname><given-names>D.</given-names></name></person-group> (<year>2014</year>). <article-title>Making the difference: integrating structural variation detection tools</article-title>. <source>Brief. Bioinform.</source><pub-id pub-id-type="doi">10.1093/bib/bbu047</pub-id><pub-id pub-id-type="pmid">25504367</pub-id></mixed-citation></ref><ref id="B62"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Luo</surname><given-names>R.</given-names></name><name><surname>Liu</surname><given-names>B.</given-names></name><name><surname>Xie</surname><given-names>Y.</given-names></name><name><surname>Li</surname><given-names>Z.</given-names></name><name><surname>Huang</surname><given-names>W.</given-names></name><name><surname>Yuan</surname><given-names>J.</given-names></name><etal></etal></person-group> (<year>2012</year>). <article-title>Soapdenovo2: an empirically improved memory-efficient short-read de novo assembler</article-title>. <source>Gigascience</source><volume>1</volume>, <fpage>18</fpage>.<pub-id pub-id-type="doi">10.1186/2047-217X-1-18</pub-id><pub-id pub-id-type="pmid">23587118</pub-id></mixed-citation></ref><ref id="B63"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Magi</surname><given-names>A.</given-names></name><name><surname>Benelli</surname><given-names>M.</given-names></name><name><surname>Marseglia</surname><given-names>G.</given-names></name><name><surname>Nannetti</surname><given-names>G.</given-names></name><name><surname>Scordo</surname><given-names>M. R.</given-names></name><name><surname>Torricelli</surname><given-names>F.</given-names></name></person-group> (<year>2010</year>). <article-title>A shifting level model algorithm that identifies aberrations in array-cgh data</article-title>. <source>Biostatistics</source><volume>11</volume>, <fpage>265</fpage>–<lpage>280</lpage>.<pub-id pub-id-type="doi">10.1093/biostatistics/kxp051</pub-id><pub-id pub-id-type="pmid">19948744</pub-id></mixed-citation></ref><ref id="B64"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Magi</surname><given-names>A.</given-names></name><name><surname>Benelli</surname><given-names>M.</given-names></name><name><surname>Yoon</surname><given-names>S.</given-names></name><name><surname>Roviello</surname><given-names>F.</given-names></name><name><surname>Torricelli</surname><given-names>F.</given-names></name></person-group> (<year>2011</year>). <article-title>Detecting common copy number variants in high-throughput sequencing data by using jointslm algorithm</article-title>. <source>Nucleic Acids Res.</source><volume>39</volume>, <fpage>e65</fpage>.<pub-id pub-id-type="doi">10.1093/nar/gkr068</pub-id><pub-id pub-id-type="pmid">21321017</pub-id></mixed-citation></ref><ref id="B65"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Magi</surname><given-names>A.</given-names></name><name><surname>Tattini</surname><given-names>L.</given-names></name><name><surname>Cifola</surname><given-names>I.</given-names></name><name><surname>D’Aurizio</surname><given-names>R.</given-names></name><name><surname>Benelli</surname><given-names>M.</given-names></name><name><surname>Mangano</surname><given-names>E.</given-names></name><etal></etal></person-group> (<year>2013</year>). <article-title>Excavator: detecting copy number variants from whole-exome sequencing data</article-title>. <source>Genome Biol.</source><volume>14</volume>, <fpage>R120</fpage>.<pub-id pub-id-type="doi">10.1186/gb-2013-14-10-r120</pub-id><pub-id pub-id-type="pmid">24172663</pub-id></mixed-citation></ref><ref id="B66"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Magi</surname><given-names>A.</given-names></name><name><surname>Tattini</surname><given-names>L.</given-names></name><name><surname>Pippucci</surname><given-names>T.</given-names></name><name><surname>Torricelli</surname><given-names>F.</given-names></name><name><surname>Benelli</surname><given-names>M.</given-names></name></person-group> (<year>2012</year>). <article-title>Read count approach for dna copy number variants detection</article-title>. <source>Bioinformatics</source><volume>28</volume>, <fpage>470</fpage>–<lpage>478</lpage>.<pub-id pub-id-type="doi">10.1093/bioinformatics/btr707</pub-id><pub-id pub-id-type="pmid">22199393</pub-id></mixed-citation></ref><ref id="B67"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Marschall</surname><given-names>T.</given-names></name><name><surname>Costa</surname><given-names>I. G.</given-names></name><name><surname>Canzar</surname><given-names>S.</given-names></name><name><surname>Bauer</surname><given-names>M.</given-names></name><name><surname>Klau</surname><given-names>G. W.</given-names></name><name><surname>Schliep</surname><given-names>A.</given-names></name><etal></etal></person-group> (<year>2012</year>). <article-title>Clever: clique-enumerating variant finder</article-title>. <source>Bioinformatics</source><volume>28</volume>, <fpage>2875</fpage>–<lpage>2882</lpage>.<pub-id pub-id-type="doi">10.1093/bioinformatics/bts566</pub-id><pub-id pub-id-type="pmid">23060616</pub-id></mixed-citation></ref><ref id="B68"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Marschall</surname><given-names>T.</given-names></name><name><surname>Hajirasouliha</surname><given-names>I.</given-names></name><name><surname>Schönhuth</surname><given-names>A.</given-names></name></person-group> (<year>2013</year>). <article-title>Mate-clever: Mendelian-inheritance-aware discovery and genotyping of midsize and long indels</article-title>. <source>Bioinformatics</source><volume>29</volume>, <fpage>3143</fpage>–<lpage>3150</lpage>.<pub-id pub-id-type="doi">10.1093/bioinformatics/btt556</pub-id><pub-id pub-id-type="pmid">24072733</pub-id></mixed-citation></ref><ref id="B69"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Medvedev</surname><given-names>P.</given-names></name><name><surname>Fiume</surname><given-names>M.</given-names></name><name><surname>Dzamba</surname><given-names>M.</given-names></name><name><surname>Smith</surname><given-names>T.</given-names></name><name><surname>Brudno</surname><given-names>M.</given-names></name></person-group> (<year>2010</year>). <article-title>Detecting copy number variation with mated short reads</article-title>. <source>Genome Res.</source><volume>20</volume>, <fpage>1613</fpage>–<lpage>1622</lpage>.<pub-id pub-id-type="doi">10.1101/gr.106344.110</pub-id><pub-id pub-id-type="pmid">20805290</pub-id></mixed-citation></ref><ref id="B70"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Metzker</surname><given-names>M. L.</given-names></name></person-group> (<year>2010</year>). <article-title>Sequencing technologies – the next generation</article-title>. <source>Nat. Rev. Genet.</source><volume>11</volume>, <fpage>31</fpage>–<lpage>46</lpage>.<pub-id pub-id-type="doi">10.1038/nrg2626</pub-id><pub-id pub-id-type="pmid">19997069</pub-id></mixed-citation></ref><ref id="B71"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Miller</surname><given-names>C. A.</given-names></name><name><surname>Hampton</surname><given-names>O.</given-names></name><name><surname>Coarfa</surname><given-names>C.</given-names></name><name><surname>Milosavljevic</surname><given-names>A.</given-names></name></person-group> (<year>2011</year>). <article-title>Readdepth: a parallel r package for detecting copy number alterations from short sequencing reads</article-title>. <source>PLoS ONE</source><volume>6</volume>:<fpage>e16327</fpage>.<pub-id pub-id-type="doi">10.1371/journal.pone.0016327</pub-id><pub-id pub-id-type="pmid">21305028</pub-id></mixed-citation></ref><ref id="B72"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mills</surname><given-names>R. E.</given-names></name><name><surname>Luttig</surname><given-names>C. T.</given-names></name><name><surname>Larkins</surname><given-names>C. E.</given-names></name><name><surname>Beauchamp</surname><given-names>A.</given-names></name><name><surname>Tsui</surname><given-names>C.</given-names></name><name><surname>Pittard</surname><given-names>W. S.</given-names></name><etal></etal></person-group> (<year>2006</year>). <article-title>An initial map of insertion and deletion (indel) variation in the human genome</article-title>. <source>Genome Res.</source><volume>16</volume>, <fpage>1182</fpage>–<lpage>1190</lpage>.<pub-id pub-id-type="doi">10.1101/gr.4565806</pub-id><pub-id pub-id-type="pmid">16902084</pub-id></mixed-citation></ref><ref id="B73"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mills</surname><given-names>R. E.</given-names></name><name><surname>Walter</surname><given-names>K.</given-names></name><name><surname>Stewart</surname><given-names>C.</given-names></name><name><surname>Handsaker</surname><given-names>R. E.</given-names></name><name><surname>Chen</surname><given-names>K.</given-names></name><name><surname>Alkan</surname><given-names>C.</given-names></name><etal></etal></person-group> (<year>2011</year>). <article-title>Mapping copy number variation by population-scale genome sequencing</article-title>. <source>Nature</source><volume>470</volume>, <fpage>59</fpage>–<lpage>65</lpage>.<pub-id pub-id-type="doi">10.1038/nature09708</pub-id><pub-id pub-id-type="pmid">21293372</pub-id></mixed-citation></ref><ref id="B74"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mimori</surname><given-names>T.</given-names></name><name><surname>Nariai</surname><given-names>N.</given-names></name><name><surname>Kojima</surname><given-names>K.</given-names></name><name><surname>Takahashi</surname><given-names>M.</given-names></name><name><surname>Ono</surname><given-names>A.</given-names></name><name><surname>Sato</surname><given-names>Y.</given-names></name><etal></etal></person-group> (<year>2013</year>). <article-title>isvp: an integrated structural variant calling pipeline from high-throughput sequencing data</article-title>. <source>BMC Syst. Biol.</source><volume>7</volume>(<issue>Suppl. 6</issue>):<fpage>S8</fpage>.<pub-id pub-id-type="doi">10.1186/1752-0509-7-S6-S8</pub-id><pub-id pub-id-type="pmid">24564972</pub-id></mixed-citation></ref><ref id="B75"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mullikin</surname><given-names>J. C.</given-names></name><name><surname>Ning</surname><given-names>Z.</given-names></name></person-group> (<year>2003</year>). <article-title>The phusion assembler</article-title>. <source>Genome Res.</source><volume>13</volume>, <fpage>81</fpage>–<lpage>90</lpage>.<pub-id pub-id-type="doi">10.1101/gr.731003</pub-id><pub-id pub-id-type="pmid">12529309</pub-id></mixed-citation></ref><ref id="B76"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Myers</surname><given-names>E. W.</given-names></name></person-group> (<year>2005</year>). <article-title>The fragment assembly string graph</article-title>. <source>Bioinformatics</source><volume>21</volume>(<issue>Suppl. 2</issue>), <fpage>ii79</fpage>–<lpage>ii85</lpage>.<pub-id pub-id-type="doi">10.1093/bioinformatics/bti1114</pub-id><pub-id pub-id-type="pmid">16204131</pub-id></mixed-citation></ref><ref id="B77"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Niedringhaus</surname><given-names>T. P.</given-names></name><name><surname>Milanova</surname><given-names>D.</given-names></name><name><surname>Kerby</surname><given-names>M. B.</given-names></name><name><surname>Snyder</surname><given-names>M. P.</given-names></name><name><surname>Barron</surname><given-names>A. E.</given-names></name></person-group> (<year>2011</year>). <article-title>Landscape of next-generation sequencing technologies</article-title>. <source>Anal. Chem.</source><volume>83</volume>, <fpage>4327</fpage>–<lpage>4341</lpage>.<pub-id pub-id-type="doi">10.1021/ac2010857</pub-id><pub-id pub-id-type="pmid">21612267</pub-id></mixed-citation></ref><ref id="B78"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Nijkamp</surname><given-names>J. F.</given-names></name><name><surname>van den Broek</surname><given-names>M. A.</given-names></name><name><surname>Geertman</surname><given-names>J.-M. A.</given-names></name><name><surname>Reinders</surname><given-names>M. J. T.</given-names></name><name><surname>Daran</surname><given-names>J.-M. G.</given-names></name><name><surname>de Ridder</surname><given-names>D.</given-names></name></person-group> (<year>2012</year>). <article-title>De novo detection of copy number variation by co-assembly</article-title>. <source>Bioinformatics</source><volume>28</volume>, <fpage>3195</fpage>–<lpage>3202</lpage>.<pub-id pub-id-type="doi">10.1093/bioinformatics/bts601</pub-id><pub-id pub-id-type="pmid">23047563</pub-id></mixed-citation></ref><ref id="B79"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ning</surname><given-names>Z.</given-names></name><name><surname>Cox</surname><given-names>A. J.</given-names></name><name><surname>Mullikin</surname><given-names>J. C.</given-names></name></person-group> (<year>2001</year>). <article-title>Ssaha: a fast search method for large dna databases</article-title>. <source>Genome Res.</source><volume>11</volume>, <fpage>1725</fpage>–<lpage>1729</lpage>.<pub-id pub-id-type="doi">10.1101/gr.194201</pub-id><pub-id pub-id-type="pmid">11591649</pub-id></mixed-citation></ref><ref id="B80"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>O’Rawe</surname><given-names>J. A.</given-names></name><name><surname>Ferson</surname><given-names>S.</given-names></name><name><surname>Lyon</surname><given-names>G. J.</given-names></name></person-group> (<year>2015</year>). <article-title>Accounting for uncertainty in dna sequencing data</article-title>. <source>Trends Genet.</source><volume>31</volume>, <fpage>61</fpage>–<lpage>66</lpage>.<pub-id pub-id-type="doi">10.1016/j.tig.2014.12.002</pub-id><pub-id pub-id-type="pmid">25579994</pub-id></mixed-citation></ref><ref id="B81"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Pabinger</surname><given-names>S.</given-names></name><name><surname>Dander</surname><given-names>A.</given-names></name><name><surname>Fischer</surname><given-names>M.</given-names></name><name><surname>Snajder</surname><given-names>R.</given-names></name><name><surname>Sperk</surname><given-names>M.</given-names></name><name><surname>Efremova</surname><given-names>M.</given-names></name><etal></etal></person-group> (<year>2014</year>). <article-title>A survey of tools for variant analysis of next-generation genome sequencing data</article-title>. <source>Brief. Bioinformatics</source><volume>15</volume>, <fpage>256</fpage>–<lpage>278</lpage>.<pub-id pub-id-type="doi">10.1093/bib/bbs086</pub-id><pub-id pub-id-type="pmid">23341494</pub-id></mixed-citation></ref><ref id="B82"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Pang</surname><given-names>A. W.</given-names></name><name><surname>MacDonald</surname><given-names>J. R.</given-names></name><name><surname>Pinto</surname><given-names>D.</given-names></name><name><surname>Wei</surname><given-names>J.</given-names></name><name><surname>Rafiq</surname><given-names>M. A.</given-names></name><name><surname>Conrad</surname><given-names>D. F.</given-names></name><etal></etal></person-group> (<year>2010</year>). <article-title>Towards a comprehensive structural variation map of an individual human genome</article-title>. <source>Genome Biol.</source><volume>11</volume>, <fpage>R52</fpage>.<pub-id pub-id-type="doi">10.1186/gb-2010-11-5-r52</pub-id><pub-id pub-id-type="pmid">20482838</pub-id></mixed-citation></ref><ref id="B83"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Pareek</surname><given-names>C. S.</given-names></name><name><surname>Smoczynski</surname><given-names>R.</given-names></name><name><surname>Tretyn</surname><given-names>A.</given-names></name></person-group> (<year>2011</year>). <article-title>Sequencing technologies and genome sequencing</article-title>. <source>J. Appl. Genet.</source><volume>52</volume>, <fpage>413</fpage>–<lpage>435</lpage>.<pub-id pub-id-type="doi">10.1007/s13353-011-0057-x</pub-id><pub-id pub-id-type="pmid">21698376</pub-id></mixed-citation></ref><ref id="B84"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Pinkel</surname><given-names>D.</given-names></name><name><surname>Segraves</surname><given-names>R.</given-names></name><name><surname>Sudar</surname><given-names>D.</given-names></name><name><surname>Clark</surname><given-names>S.</given-names></name><name><surname>Poole</surname><given-names>I.</given-names></name><name><surname>Kowbel</surname><given-names>D.</given-names></name><etal></etal></person-group> (<year>1998</year>). <article-title>High resolution analysis of dna copy number variation using comparative genomic hybridization to microarrays</article-title>. <source>Nat. Genet.</source><volume>20</volume>, <fpage>207</fpage>–<lpage>211</lpage>.<pub-id pub-id-type="doi">10.1038/2524</pub-id><pub-id pub-id-type="pmid">9771718</pub-id></mixed-citation></ref><ref id="B85"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Qi</surname><given-names>J.</given-names></name><name><surname>Zhao</surname><given-names>F.</given-names></name></person-group> (<year>2011</year>). <article-title>ingap-sv: a novel scheme to identify and visualize structural variation from paired end mapping data</article-title>. <source>Nucleic Acids Res.</source><volume>39</volume>, <fpage>W567</fpage>–<lpage>W575</lpage>.<pub-id pub-id-type="doi">10.1093/nar/gkr506</pub-id><pub-id pub-id-type="pmid">21715388</pub-id></mixed-citation></ref><ref id="B86"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Quail</surname><given-names>M. A.</given-names></name><name><surname>Smith</surname><given-names>M.</given-names></name><name><surname>Coupland</surname><given-names>P.</given-names></name><name><surname>Otto</surname><given-names>T. D.</given-names></name><name><surname>Harris</surname><given-names>S. R.</given-names></name><name><surname>Connor</surname><given-names>T. R.</given-names></name><etal></etal></person-group> (<year>2012</year>). <article-title>A tale of three next generation sequencing platforms: comparison of ion torrent, pacific biosciences and illumina miseq sequencers</article-title>. <source>BMC Genomics</source><volume>13</volume>:<fpage>341</fpage>.<pub-id pub-id-type="doi">10.1186/1471-2164-13-341</pub-id><pub-id pub-id-type="pmid">22827831</pub-id></mixed-citation></ref><ref id="B87"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Quick</surname><given-names>J.</given-names></name><name><surname>Quinlan</surname><given-names>A. R.</given-names></name><name><surname>Loman</surname><given-names>N. J.</given-names></name></person-group> (<year>2014</year>). <article-title>A reference bacterial genome dataset generated on the minion™ portable single-molecule nanopore sequencer</article-title>. <source>Gigascience</source><volume>3</volume>, <fpage>22</fpage><pub-id pub-id-type="doi">10.1186/2047-217X-3-22</pub-id><pub-id pub-id-type="pmid">25386338</pub-id></mixed-citation></ref><ref id="B88"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Quinlan</surname><given-names>A. R.</given-names></name><name><surname>Clark</surname><given-names>R. A.</given-names></name><name><surname>Sokolova</surname><given-names>S.</given-names></name><name><surname>Leibowitz</surname><given-names>M. L.</given-names></name><name><surname>Zhang</surname><given-names>Y.</given-names></name><name><surname>Hurles</surname><given-names>M. E.</given-names></name><etal></etal></person-group> (<year>2010</year>). <article-title>Genome-wide mapping and assembly of structural variant breakpoints in the mouse genome</article-title>. <source>Genome Res.</source><volume>20</volume>, <fpage>623</fpage>–<lpage>635</lpage>.<pub-id pub-id-type="doi">10.1101/gr.102970.109</pub-id><pub-id pub-id-type="pmid">20308636</pub-id></mixed-citation></ref><ref id="B89"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Rausch</surname><given-names>T.</given-names></name><name><surname>Zichner</surname><given-names>T.</given-names></name><name><surname>Schlattl</surname><given-names>A.</given-names></name><name><surname>Stütz</surname><given-names>A. M.</given-names></name><name><surname>Benes</surname><given-names>V.</given-names></name><name><surname>Korbel</surname><given-names>J. O.</given-names></name></person-group> (<year>2012</year>). <article-title>Delly: structural variant discovery by integrated paired-end and split-read analysis</article-title>. <source>Bioinformatics</source><volume>28</volume>, <fpage>i333</fpage>–<lpage>i339</lpage>.<pub-id pub-id-type="doi">10.1093/bioinformatics/bts378</pub-id><pub-id pub-id-type="pmid">22962449</pub-id></mixed-citation></ref><ref id="B90"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Samarakoon</surname><given-names>P. S.</given-names></name><name><surname>Sorte</surname><given-names>H. S.</given-names></name><name><surname>Kristiansen</surname><given-names>B. E.</given-names></name><name><surname>Skodje</surname><given-names>T.</given-names></name><name><surname>Sheng</surname><given-names>Y.</given-names></name><name><surname>Tjønnfjord</surname><given-names>G. E.</given-names></name><etal></etal></person-group> (<year>2014</year>). <article-title>Identification of copy number variants from exome sequence data</article-title>. <source>BMC Genomics</source><volume>15</volume>:<fpage>661</fpage>.<pub-id pub-id-type="doi">10.1186/1471-2164-15-661</pub-id><pub-id pub-id-type="pmid">25102989</pub-id></mixed-citation></ref><ref id="B91"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sathirapongsasuti</surname><given-names>J. F.</given-names></name><name><surname>Lee</surname><given-names>H.</given-names></name><name><surname>Horst</surname><given-names>B. A. J.</given-names></name><name><surname>Brunner</surname><given-names>G.</given-names></name><name><surname>Cochran</surname><given-names>A. J.</given-names></name><name><surname>Binder</surname><given-names>S.</given-names></name><etal></etal></person-group> (<year>2011</year>). <article-title>Exome sequencing-based copy-number variation and loss of heterozygosity detection: Exomecnv</article-title>. <source>Bioinformatics</source><volume>27</volume>, <fpage>2648</fpage>–<lpage>2654</lpage>.<pub-id pub-id-type="doi">10.1093/bioinformatics/btr462</pub-id><pub-id pub-id-type="pmid">21828086</pub-id></mixed-citation></ref><ref id="B92"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Schadt</surname><given-names>E. E.</given-names></name><name><surname>Turner</surname><given-names>S.</given-names></name><name><surname>Kasarskis</surname><given-names>A.</given-names></name></person-group> (<year>2010</year>). <article-title>A window into third-generation sequencing</article-title>. <source>Hum. Mol. Genet.</source><volume>19</volume>, <fpage>R227</fpage>–<lpage>R240</lpage>.<pub-id pub-id-type="doi">10.1093/hmg/ddq416</pub-id><pub-id pub-id-type="pmid">20858600</pub-id></mixed-citation></ref><ref id="B93"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Schröder</surname><given-names>J.</given-names></name><name><surname>Hsu</surname><given-names>A.</given-names></name><name><surname>Boyle</surname><given-names>S. E.</given-names></name><name><surname>Macintyre</surname><given-names>G.</given-names></name><name><surname>Cmero</surname><given-names>M.</given-names></name><name><surname>Tothill</surname><given-names>R. W.</given-names></name><etal></etal></person-group> (<year>2014</year>). <article-title>Socrates: identification of genomic rearrangements in tumour genomes by re-aligning soft clipped reads</article-title>. <source>Bioinformatics</source>. <volume>30</volume>, <fpage>1064</fpage>–<lpage>1072</lpage>.<pub-id pub-id-type="doi">10.1093/bioinformatics/btt767</pub-id><pub-id pub-id-type="pmid">24389656</pub-id></mixed-citation></ref><ref id="B94"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sebat</surname><given-names>J.</given-names></name><name><surname>Lakshmi</surname><given-names>B.</given-names></name><name><surname>Malhotra</surname><given-names>D.</given-names></name><name><surname>Troge</surname><given-names>J.</given-names></name><name><surname>Lese-Martin</surname><given-names>C.</given-names></name><name><surname>Walsh</surname><given-names>T.</given-names></name><etal></etal></person-group> (<year>2007</year>). <article-title>Strong association of de novo copy number mutations with autism</article-title>. <source>Science</source><volume>316</volume>, <fpage>445</fpage>–<lpage>449</lpage>.<pub-id pub-id-type="doi">10.1126/science.1138659</pub-id><pub-id pub-id-type="pmid">17363630</pub-id></mixed-citation></ref><ref id="B95"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Shendure</surname><given-names>J.</given-names></name><name><surname>Ji</surname><given-names>H.</given-names></name></person-group> (<year>2008</year>). <article-title>Next-generation dna sequencing</article-title>. <source>Nat. Biotechnol.</source><volume>26</volume>, <fpage>1135</fpage>–<lpage>1145</lpage>.<pub-id pub-id-type="doi">10.1038/nbt1486</pub-id><pub-id pub-id-type="pmid">18846087</pub-id></mixed-citation></ref><ref id="B96"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Shendure</surname><given-names>J. A.</given-names></name><name><surname>Porreca</surname><given-names>G. J.</given-names></name><name><surname>Church</surname><given-names>G. M.</given-names></name><name><surname>Gardner</surname><given-names>A. F.</given-names></name><name><surname>Hendrickson</surname><given-names>C. L.</given-names></name><name><surname>Kieleczawa</surname><given-names>J.</given-names></name><etal></etal></person-group> (<year>2011</year>). <article-title>Overview of dna sequencing strategies</article-title>. <source>Curr. Protoc. Mol. Biol.</source> Chapter 7, Unit7.1.<pub-id pub-id-type="doi">10.1002/0471142727.mb0701s96</pub-id><pub-id pub-id-type="pmid">21987056</pub-id></mixed-citation></ref><ref id="B97"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Simpson</surname><given-names>J. T.</given-names></name><name><surname>Durbin</surname><given-names>R.</given-names></name></person-group> (<year>2010</year>). <article-title>Efficient construction of an assembly string graph using the fm-index</article-title>. <source>Bioinformatics</source><volume>26</volume>, <fpage>i367</fpage>–<lpage>i373</lpage>.<pub-id pub-id-type="doi">10.1093/bioinformatics/btq217</pub-id><pub-id pub-id-type="pmid">20529929</pub-id></mixed-citation></ref><ref id="B98"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Simpson</surname><given-names>J. T.</given-names></name><name><surname>Durbin</surname><given-names>R.</given-names></name></person-group> (<year>2012</year>). <article-title>Efficient de novo assembly of large genomes using compressed data structures</article-title>. <source>Genome Res.</source><volume>22</volume>, <fpage>549</fpage>–<lpage>556</lpage>.<pub-id pub-id-type="doi">10.1101/gr.126953.111</pub-id><pub-id pub-id-type="pmid">22156294</pub-id></mixed-citation></ref><ref id="B99"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sindi</surname><given-names>S.</given-names></name><name><surname>Helman</surname><given-names>E.</given-names></name><name><surname>Bashir</surname><given-names>A.</given-names></name><name><surname>Raphael</surname><given-names>B. J.</given-names></name></person-group> (<year>2009</year>). <article-title>A geometric approach for classification and comparison of structural variants</article-title>. <source>Bioinformatics</source><volume>25</volume>, <fpage>i222</fpage>–<lpage>i230</lpage>.<pub-id pub-id-type="doi">10.1093/bioinformatics/btp208</pub-id><pub-id pub-id-type="pmid">19477992</pub-id></mixed-citation></ref><ref id="B100"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sindi</surname><given-names>S. S.</given-names></name><name><surname>Onal</surname><given-names>S.</given-names></name><name><surname>Peng</surname><given-names>L. C.</given-names></name><name><surname>Wu</surname><given-names>H.-T.</given-names></name><name><surname>Raphael</surname><given-names>B. J.</given-names></name></person-group> (<year>2012</year>). <article-title>An integrative probabilistic model for identification of structural variation in sequencing data</article-title>. <source>Genome Biol.</source><volume>13</volume>, <fpage>R22</fpage>.<pub-id pub-id-type="doi">10.1186/gb-2012-13-3-r22</pub-id><pub-id pub-id-type="pmid">22452995</pub-id></mixed-citation></ref><ref id="B101"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Snijders</surname><given-names>A. M.</given-names></name><name><surname>Nowak</surname><given-names>N.</given-names></name><name><surname>Segraves</surname><given-names>R.</given-names></name><name><surname>Blackwood</surname><given-names>S.</given-names></name><name><surname>Brown</surname><given-names>N.</given-names></name><name><surname>Conroy</surname><given-names>J.</given-names></name><etal></etal></person-group> (<year>2001</year>). <article-title>Assembly of microarrays for genome-wide measurement of dna copy number</article-title>. <source>Nat. Genet.</source><volume>29</volume>, <fpage>263</fpage>–<lpage>264</lpage>.<pub-id pub-id-type="doi">10.1038/ng754</pub-id><pub-id pub-id-type="pmid">11687795</pub-id></mixed-citation></ref><ref id="B102"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Tan</surname><given-names>R.</given-names></name><name><surname>Wang</surname><given-names>Y.</given-names></name><name><surname>Kleinstein</surname><given-names>S. E.</given-names></name><name><surname>Liu</surname><given-names>Y.</given-names></name><name><surname>Zhu</surname><given-names>X.</given-names></name><name><surname>Guo</surname><given-names>H.</given-names></name><etal></etal></person-group> (<year>2014</year>). <article-title>An evaluation of copy number variation detection tools from whole-exome sequencing data</article-title>. <source>Hum. Mutat.</source><volume>35</volume>, <fpage>899</fpage>–<lpage>907</lpage>.<pub-id pub-id-type="doi">10.1002/humu.22537</pub-id><pub-id pub-id-type="pmid">24599517</pub-id></mixed-citation></ref><ref id="B103"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Teo</surname><given-names>S. M.</given-names></name><name><surname>Pawitan</surname><given-names>Y.</given-names></name><name><surname>Ku</surname><given-names>C. S.</given-names></name><name><surname>Chia</surname><given-names>K. S.</given-names></name><name><surname>Salim</surname><given-names>A.</given-names></name></person-group> (<year>2012</year>). <article-title>Statistical challenges associated with detecting copy number variations with next-generation sequencing</article-title>. <source>Bioinformatics</source><volume>28</volume>, <fpage>2711</fpage>–<lpage>2718</lpage>.<pub-id pub-id-type="doi">10.1093/bioinformatics/bts535</pub-id><pub-id pub-id-type="pmid">22942022</pub-id></mixed-citation></ref><ref id="B104"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Thung</surname><given-names>D.</given-names></name><name><surname>de Ligt</surname><given-names>J.</given-names></name><name><surname>Vissers</surname><given-names>L.</given-names></name><name><surname>Steehouwer</surname><given-names>M.</given-names></name><name><surname>Kroon</surname><given-names>M.</given-names></name><name><surname>de Vries</surname><given-names>P.</given-names></name><etal></etal></person-group> (<year>2014</year>). <article-title>Mobster: accurate detection of mobile element insertions in next generation sequencing data</article-title>. <source>Genome Biol.</source><volume>15</volume>, <fpage>488</fpage>.<pub-id pub-id-type="doi">10.1186/s13059-014-0488-x</pub-id><pub-id pub-id-type="pmid">25348035</pub-id></mixed-citation></ref><ref id="B105"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Trappe</surname><given-names>K.</given-names></name><name><surname>Emde</surname><given-names>A.-K.</given-names></name><name><surname>Ehrlich</surname><given-names>H.-C.</given-names></name><name><surname>Reinert</surname><given-names>K.</given-names></name></person-group> (<year>2014</year>). <article-title>Gustaf: detecting and correctly classifying SVs in the NGS twilight zone</article-title>. <source>Bioinformatics</source><volume>30</volume>, <fpage>3484</fpage>–<lpage>3490</lpage>.<pub-id pub-id-type="doi">10.1093/bioinformatics/btu431</pub-id><pub-id pub-id-type="pmid">25028727</pub-id></mixed-citation></ref><ref id="B106"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Venkatesan</surname><given-names>B. M.</given-names></name><name><surname>Bashir</surname><given-names>R.</given-names></name></person-group> (<year>2011</year>). <article-title>Nanopore sensors for nucleic acid analysis</article-title>. <source>Nat. Nanotechnol.</source><volume>6</volume>, <fpage>615</fpage>–<lpage>624</lpage>.<pub-id pub-id-type="doi">10.1038/nnano.2011.129</pub-id><pub-id pub-id-type="pmid">21926981</pub-id></mixed-citation></ref><ref id="B107"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Venkatraman</surname><given-names>E. S.</given-names></name><name><surname>Olshen</surname><given-names>A. B.</given-names></name></person-group> (<year>2007</year>). <article-title>A faster circular binary segmentation algorithm for the analysis of array cgh data</article-title>. <source>Bioinformatics</source><volume>23</volume>, <fpage>657</fpage>–<lpage>663</lpage>.<pub-id pub-id-type="doi">10.1093/bioinformatics/btl646</pub-id><pub-id pub-id-type="pmid">17234643</pub-id></mixed-citation></ref><ref id="B108"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Voelkerding</surname><given-names>K. V.</given-names></name><name><surname>Dames</surname><given-names>S. A.</given-names></name><name><surname>Durtschi</surname><given-names>J. D.</given-names></name></person-group> (<year>2009</year>). <article-title>Next-generation sequencing: from basic research to diagnostics</article-title>. <source>Clin. Chem.</source><volume>55</volume>, <fpage>641</fpage>–<lpage>658</lpage>.<pub-id pub-id-type="doi">10.1373/clinchem.2008.112789</pub-id><pub-id pub-id-type="pmid">19246620</pub-id></mixed-citation></ref><ref id="B109"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wang</surname><given-names>J.</given-names></name><name><surname>Mullighan</surname><given-names>C. G.</given-names></name><name><surname>Easton</surname><given-names>J.</given-names></name><name><surname>Roberts</surname><given-names>S.</given-names></name><name><surname>Heatley</surname><given-names>S. L.</given-names></name><name><surname>Ma</surname><given-names>J.</given-names></name><etal></etal></person-group> (<year>2011</year>). <article-title>Crest maps somatic structural variation in cancer genomes with base-pair resolution</article-title>. <source>Nat. Methods</source><volume>8</volume>, <fpage>652</fpage>–<lpage>654</lpage>.<pub-id pub-id-type="doi">10.1038/nmeth.1628</pub-id><pub-id pub-id-type="pmid">21666668</pub-id></mixed-citation></ref><ref id="B110"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wong</surname><given-names>K.</given-names></name><name><surname>Keane</surname><given-names>T. M.</given-names></name><name><surname>Stalker</surname><given-names>J.</given-names></name><name><surname>Adams</surname><given-names>D. J.</given-names></name></person-group> (<year>2010</year>). <article-title>Enhanced structural variant and breakpoint detection using svmerge by integration of multiple detection methods and local assembly</article-title>. <source>Genome Biol.</source><volume>11</volume>, <fpage>R128</fpage>.<pub-id pub-id-type="doi">10.1186/gb-2010-11-12-r128</pub-id><pub-id pub-id-type="pmid">21194472</pub-id></mixed-citation></ref><ref id="B111"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wu</surname><given-names>J.</given-names></name><name><surname>Lee</surname><given-names>W.-P.</given-names></name><name><surname>Ward</surname><given-names>A.</given-names></name><name><surname>Walker</surname><given-names>J. A.</given-names></name><name><surname>Konkel</surname><given-names>M. K.</given-names></name><name><surname>Batzer</surname><given-names>M. A.</given-names></name><etal></etal></person-group> (<year>2014</year>). <article-title>Tangram: a comprehensive toolbox for mobile element insertion detection</article-title>. <source>BMC Genomics</source><volume>15</volume>:<fpage>795</fpage>.<pub-id pub-id-type="doi">10.1186/1471-2164-15-795</pub-id><pub-id pub-id-type="pmid">25228379</pub-id></mixed-citation></ref><ref id="B112"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Xi</surname><given-names>R.</given-names></name><name><surname>Hadjipanayis</surname><given-names>A. G.</given-names></name><name><surname>Luquette</surname><given-names>L. J.</given-names></name><name><surname>Kim</surname><given-names>T.-M.</given-names></name><name><surname>Lee</surname><given-names>E.</given-names></name><name><surname>Zhang</surname><given-names>J.</given-names></name><etal></etal></person-group> (<year>2011</year>). <article-title>Copy number variation detection in whole-genome sequencing data using the bayesian information criterion</article-title>. <source>Proc. Natl. Acad. Sci. U.S.A.</source><volume>108</volume>, <fpage>E1128</fpage>–<lpage>E1136</lpage>.<pub-id pub-id-type="doi">10.1073/pnas.1110574108</pub-id><pub-id pub-id-type="pmid">22065754</pub-id></mixed-citation></ref><ref id="B113"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Xie</surname><given-names>C.</given-names></name><name><surname>Tammi</surname><given-names>M. T.</given-names></name></person-group> (<year>2009</year>). <article-title>Cnv-seq, a new method to detect copy number variation using high-throughput sequencing</article-title>. <source>BMC Bioinformatics</source><volume>10</volume>:<fpage>80</fpage>.<pub-id pub-id-type="doi">10.1186/1471-2105-10-80</pub-id><pub-id pub-id-type="pmid">19267900</pub-id></mixed-citation></ref><ref id="B114"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ye</surname><given-names>K.</given-names></name><name><surname>Schulz</surname><given-names>M. H.</given-names></name><name><surname>Long</surname><given-names>Q.</given-names></name><name><surname>Apweiler</surname><given-names>R.</given-names></name><name><surname>Ning</surname><given-names>Z.</given-names></name></person-group> (<year>2009</year>). <article-title>Pindel: a pattern growth approach to detect break points of large deletions and medium sized insertions from paired-end short reads</article-title>. <source>Bioinformatics</source><volume>25</volume>, <fpage>2865</fpage>–<lpage>2871</lpage>.<pub-id pub-id-type="doi">10.1093/bioinformatics/btp394</pub-id><pub-id pub-id-type="pmid">19561018</pub-id></mixed-citation></ref><ref id="B115"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Yoon</surname><given-names>S.</given-names></name><name><surname>Xuan</surname><given-names>Z.</given-names></name><name><surname>Makarov</surname><given-names>V.</given-names></name><name><surname>Ye</surname><given-names>K.</given-names></name><name><surname>Sebat</surname><given-names>J.</given-names></name></person-group> (<year>2009</year>). <article-title>Sensitive and accurate detection of copy number variants using read depth of coverage</article-title>. <source>Genome Res.</source><volume>19</volume>, <fpage>1586</fpage>–<lpage>1592</lpage>.<pub-id pub-id-type="doi">10.1101/gr.092981.109</pub-id><pub-id pub-id-type="pmid">19657104</pub-id></mixed-citation></ref><ref id="B116"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Zeitouni</surname><given-names>B.</given-names></name><name><surname>Boeva</surname><given-names>V.</given-names></name><name><surname>Janoueix-Lerosey</surname><given-names>I.</given-names></name><name><surname>Loeillet</surname><given-names>S.</given-names></name><name><surname>Legoix-né</surname><given-names>P.</given-names></name><name><surname>Nicolas</surname><given-names>A.</given-names></name><etal></etal></person-group> (<year>2010</year>). <article-title>Svdetect: a tool to identify genomic structural variations from paired-end and mate-pair sequencing data</article-title>. <source>Bioinformatics</source><volume>26</volume>, <fpage>1895</fpage>–<lpage>1896</lpage>.<pub-id pub-id-type="doi">10.1093/bioinformatics/btq293</pub-id><pub-id pub-id-type="pmid">20639544</pub-id></mixed-citation></ref><ref id="B117"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Zhang</surname><given-names>F.</given-names></name><name><surname>Gu</surname><given-names>W.</given-names></name><name><surname>Hurles</surname><given-names>M. E.</given-names></name><name><surname>Lupski</surname><given-names>J. R.</given-names></name></person-group> (<year>2009</year>). <article-title>Copy number variation in human health, disease, and evolution</article-title>. <source>Annu. Rev. Genomics Hum. Genet.</source><volume>10</volume>, <fpage>451</fpage>–<lpage>481</lpage>.<pub-id pub-id-type="doi">10.1146/annurev.genom.9.081307.164217</pub-id><pub-id pub-id-type="pmid">19715442</pub-id></mixed-citation></ref><ref id="B118"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Zhang</surname><given-names>J.</given-names></name><name><surname>Wu</surname><given-names>Y.</given-names></name></person-group> (<year>2011</year>). <article-title>Svseq: an approach for detecting exact breakpoints of deletions with low-coverage sequence data</article-title>. <source>Bioinformatics</source><volume>27</volume>, <fpage>3228</fpage>–<lpage>3234</lpage>.<pub-id pub-id-type="doi">10.1093/bioinformatics/btr563</pub-id><pub-id pub-id-type="pmid">21994222</pub-id></mixed-citation></ref><ref id="B119"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Zhao</surname><given-names>M.</given-names></name><name><surname>Wang</surname><given-names>Q.</given-names></name><name><surname>Wang</surname><given-names>Q.</given-names></name><name><surname>Jia</surname><given-names>P.</given-names></name><name><surname>Zhao</surname><given-names>Z.</given-names></name></person-group> (<year>2013</year>). <article-title>Computational tools for copy number variation (CNV) detection using next-generation sequencing data: features and perspectives</article-title>. <source>BMC Bioinformatics</source><volume>14</volume>(<issue>Suppl. 11</issue>):<fpage>S1</fpage>.<pub-id pub-id-type="doi">10.1186/1471-2105-14-S11-S1</pub-id><pub-id pub-id-type="pmid">24564169</pub-id></mixed-citation></ref></ref-list></back></pmc></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Ticri/CIDE/explor/TelematiV1/Data/Pmc/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000052 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Pmc/Corpus/biblio.hfd -nk 000052 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Ticri/CIDE
|area= TelematiV1
|flux= Pmc
|étape= Corpus
|type= RBID
|clé= PMC:4479793
|texte= Detection of Genomic Structural Variants from Next-Generation Sequencing Data
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Pmc/Corpus/RBID.i -Sk "pubmed:26161383" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Pmc/Corpus/biblio.hfd \
| NlmPubMed2Wicri -a TelematiV1
| This area was generated with Dilib version V0.6.31. |  |