Sequence characteristics define trade-offs between on-target and genome-wide off-target hybridization of oligoprobes.
Identifieur interne : 000859 ( PubMed/Corpus ); précédent : 000858; suivant : 000860Sequence characteristics define trade-offs between on-target and genome-wide off-target hybridization of oligoprobes.
Auteurs : Olga V. Matveeva ; Aleksey Y. Ogurtsov ; Nafisa N. Nazipova ; Svetlana A. ShabalinaSource :
- PloS one [ 1932-6203 ] ; 2018.
English descriptors
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Abstract
Off-target oligoprobe's interaction with partially complementary nucleotide sequences represents a problem for many bio-techniques. The goal of the study was to identify oligoprobe sequence characteristics that control the ratio between on-target and off-target hybridization. To understand the complex interplay between specific and genome-wide off-target (cross-hybridization) signals, we analyzed a database derived from genomic comparison hybridization experiments performed with an Affymetrix tiling array. The database included two types of probes with signals derived from (i) a combination of specific signal and cross-hybridization and (ii) genomic cross-hybridization only. All probes from the database were grouped into bins according to their sequence characteristics, where both hybridization signals were averaged separately. For selection of specific probes, we analyzed the following sequence characteristics: vulnerability to self-folding, nucleotide composition bias, numbers of G nucleotides and GGG-blocks, and occurrence of probe's k-mers in the human genome. Increases in bin ranges for these characteristics are simultaneously accompanied by a decrease in hybridization specificity-the ratio between specific and cross-hybridization signals. However, both averaged hybridization signals exhibit growing trends along with an increase of probes' binding energy, where the hybridization specific signal increases significantly faster in comparison to the cross-hybridization. The same trend is evident for the S function, which serves as a combined evaluation of probe binding energy and occurrence of probe's k-mers in the genome. Application of S allows extracting a larger number of specific probes, as compared to using only binding energy. Thus, we showed that high values of specific and cross-hybridization signals are not mutually exclusive for probes with high values of binding energy and S. In this study, the application of a new set of sequence characteristics allows detection of probes that are highly specific to their targets for array design and other bio-techniques that require selection of specific probes.
DOI: 10.1371/journal.pone.0199162
PubMed: 29928000
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Sequence characteristics define trade-offs between on-target and genome-wide off-target hybridization of oligoprobes.</title><author><name sortKey="Matveeva, Olga V" sort="Matveeva, Olga V" uniqKey="Matveeva O" first="Olga V" last="Matveeva">Olga V. Matveeva</name><affiliation><nlm:affiliation>Biopolymer Design LLC, Acton, Massachusetts, United States of America.</nlm:affiliation></affiliation></author><author><name sortKey="Ogurtsov, Aleksey Y" sort="Ogurtsov, Aleksey Y" uniqKey="Ogurtsov A" first="Aleksey Y" last="Ogurtsov">Aleksey Y. Ogurtsov</name><affiliation><nlm:affiliation>National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland, United States of America.</nlm:affiliation></affiliation></author><author><name sortKey="Nazipova, Nafisa N" sort="Nazipova, Nafisa N" uniqKey="Nazipova N" first="Nafisa N" last="Nazipova">Nafisa N. Nazipova</name><affiliation><nlm:affiliation>Institute of Mathematical Problems of Biology, RAS - the Branch of Keldysh Institute of Applied Mathematics of Russian Academy of Sciences, Pushchino, Moscow Region, Russia.</nlm:affiliation></affiliation></author><author><name sortKey="Shabalina, Svetlana A" sort="Shabalina, Svetlana A" uniqKey="Shabalina S" first="Svetlana A" last="Shabalina">Svetlana A. Shabalina</name><affiliation><nlm:affiliation>National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland, United States of America.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2018">2018</date><idno type="RBID">pubmed:29928000</idno><idno type="pmid">29928000</idno><idno type="doi">10.1371/journal.pone.0199162</idno><idno type="wicri:Area/PubMed/Corpus">000859</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000859</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Sequence characteristics define trade-offs between on-target and genome-wide off-target hybridization of oligoprobes.</title><author><name sortKey="Matveeva, Olga V" sort="Matveeva, Olga V" uniqKey="Matveeva O" first="Olga V" last="Matveeva">Olga V. Matveeva</name><affiliation><nlm:affiliation>Biopolymer Design LLC, Acton, Massachusetts, United States of America.</nlm:affiliation></affiliation></author><author><name sortKey="Ogurtsov, Aleksey Y" sort="Ogurtsov, Aleksey Y" uniqKey="Ogurtsov A" first="Aleksey Y" last="Ogurtsov">Aleksey Y. Ogurtsov</name><affiliation><nlm:affiliation>National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland, United States of America.</nlm:affiliation></affiliation></author><author><name sortKey="Nazipova, Nafisa N" sort="Nazipova, Nafisa N" uniqKey="Nazipova N" first="Nafisa N" last="Nazipova">Nafisa N. Nazipova</name><affiliation><nlm:affiliation>Institute of Mathematical Problems of Biology, RAS - the Branch of Keldysh Institute of Applied Mathematics of Russian Academy of Sciences, Pushchino, Moscow Region, Russia.</nlm:affiliation></affiliation></author><author><name sortKey="Shabalina, Svetlana A" sort="Shabalina, Svetlana A" uniqKey="Shabalina S" first="Svetlana A" last="Shabalina">Svetlana A. Shabalina</name><affiliation><nlm:affiliation>National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland, United States of America.</nlm:affiliation></affiliation></author></analytic><series><title level="j">PloS one</title><idno type="eISSN">1932-6203</idno><imprint><date when="2018" type="published">2018</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Base Sequence</term><term>Databases, Genetic</term><term>Genome</term><term>Humans</term><term>Nucleic Acid Hybridization</term><term>Oligonucleotide Array Sequence Analysis (methods)</term></keywords><keywords scheme="MESH" qualifier="methods" xml:lang="en"><term>Oligonucleotide Array Sequence Analysis</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Base Sequence</term><term>Databases, Genetic</term><term>Genome</term><term>Humans</term><term>Nucleic Acid Hybridization</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Off-target oligoprobe's interaction with partially complementary nucleotide sequences represents a problem for many bio-techniques. The goal of the study was to identify oligoprobe sequence characteristics that control the ratio between on-target and off-target hybridization. To understand the complex interplay between specific and genome-wide off-target (cross-hybridization) signals, we analyzed a database derived from genomic comparison hybridization experiments performed with an Affymetrix tiling array. The database included two types of probes with signals derived from (i) a combination of specific signal and cross-hybridization and (ii) genomic cross-hybridization only. All probes from the database were grouped into bins according to their sequence characteristics, where both hybridization signals were averaged separately. For selection of specific probes, we analyzed the following sequence characteristics: vulnerability to self-folding, nucleotide composition bias, numbers of G nucleotides and GGG-blocks, and occurrence of probe's k-mers in the human genome. Increases in bin ranges for these characteristics are simultaneously accompanied by a decrease in hybridization specificity-the ratio between specific and cross-hybridization signals. However, both averaged hybridization signals exhibit growing trends along with an increase of probes' binding energy, where the hybridization specific signal increases significantly faster in comparison to the cross-hybridization. The same trend is evident for the S function, which serves as a combined evaluation of probe binding energy and occurrence of probe's k-mers in the genome. Application of S allows extracting a larger number of specific probes, as compared to using only binding energy. Thus, we showed that high values of specific and cross-hybridization signals are not mutually exclusive for probes with high values of binding energy and S. In this study, the application of a new set of sequence characteristics allows detection of probes that are highly specific to their targets for array design and other bio-techniques that require selection of specific probes.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">29928000</PMID><DateCompleted><Year>2018</Year><Month>12</Month><Day>31</Day></DateCompleted><DateRevised><Year>2018</Year><Month>12</Month><Day>31</Day></DateRevised><Article PubModel="Electronic-eCollection"><Journal><ISSN IssnType="Electronic">1932-6203</ISSN><JournalIssue CitedMedium="Internet"><Volume>13</Volume><Issue>6</Issue><PubDate><Year>2018</Year></PubDate></JournalIssue><Title>PloS one</Title><ISOAbbreviation>PLoS ONE</ISOAbbreviation></Journal><ArticleTitle>Sequence characteristics define trade-offs between on-target and genome-wide off-target hybridization of oligoprobes.</ArticleTitle><Pagination><MedlinePgn>e0199162</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1371/journal.pone.0199162</ELocationID><Abstract><AbstractText>Off-target oligoprobe's interaction with partially complementary nucleotide sequences represents a problem for many bio-techniques. The goal of the study was to identify oligoprobe sequence characteristics that control the ratio between on-target and off-target hybridization. To understand the complex interplay between specific and genome-wide off-target (cross-hybridization) signals, we analyzed a database derived from genomic comparison hybridization experiments performed with an Affymetrix tiling array. The database included two types of probes with signals derived from (i) a combination of specific signal and cross-hybridization and (ii) genomic cross-hybridization only. All probes from the database were grouped into bins according to their sequence characteristics, where both hybridization signals were averaged separately. For selection of specific probes, we analyzed the following sequence characteristics: vulnerability to self-folding, nucleotide composition bias, numbers of G nucleotides and GGG-blocks, and occurrence of probe's k-mers in the human genome. Increases in bin ranges for these characteristics are simultaneously accompanied by a decrease in hybridization specificity-the ratio between specific and cross-hybridization signals. However, both averaged hybridization signals exhibit growing trends along with an increase of probes' binding energy, where the hybridization specific signal increases significantly faster in comparison to the cross-hybridization. The same trend is evident for the S function, which serves as a combined evaluation of probe binding energy and occurrence of probe's k-mers in the genome. Application of S allows extracting a larger number of specific probes, as compared to using only binding energy. Thus, we showed that high values of specific and cross-hybridization signals are not mutually exclusive for probes with high values of binding energy and S. In this study, the application of a new set of sequence characteristics allows detection of probes that are highly specific to their targets for array design and other bio-techniques that require selection of specific probes.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Matveeva</LastName><ForeName>Olga V</ForeName><Initials>OV</Initials><AffiliationInfo><Affiliation>Biopolymer Design LLC, Acton, Massachusetts, United States of America.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ogurtsov</LastName><ForeName>Aleksey Y</ForeName><Initials>AY</Initials><AffiliationInfo><Affiliation>National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland, United States of America.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Nazipova</LastName><ForeName>Nafisa N</ForeName><Initials>NN</Initials><AffiliationInfo><Affiliation>Institute of Mathematical Problems of Biology, RAS - the Branch of Keldysh Institute of Applied Mathematics of Russian Academy of Sciences, Pushchino, Moscow Region, Russia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Shabalina</LastName><ForeName>Svetlana A</ForeName><Initials>SA</Initials><Identifier Source="ORCID">0000-0002-3774-819X</Identifier><AffiliationInfo><Affiliation>National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland, United States of America.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D052060">Research Support, N.I.H., Intramural</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2018</Year><Month>06</Month><Day>21</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>PLoS One</MedlineTA><NlmUniqueID>101285081</NlmUniqueID><ISSNLinking>1932-6203</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D001483" MajorTopicYN="N">Base Sequence</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D030541" MajorTopicYN="N">Databases, Genetic</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016678" MajorTopicYN="N">Genome</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009693" MajorTopicYN="Y">Nucleic Acid Hybridization</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D020411" MajorTopicYN="N">Oligonucleotide Array Sequence Analysis</DescriptorName><QualifierName UI="Q000379" 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