More complete gene silencing by fewer siRNAs: transparent optimized design and biophysical signature
Identifieur interne : 000017 ( Ncbi/Merge ); précédent : 000016; suivant : 000018More complete gene silencing by fewer siRNAs: transparent optimized design and biophysical signature
Auteurs : Istvan LadungaSource :
- Nucleic Acids Research [ 0305-1048 ] ; 2006.
Abstract
Highly accurate knockdown functional analyses based on RNA interference (RNAi) require the possible most complete hydrolysis of the targeted mRNA while avoiding the degradation of untargeted genes (off-target effects). This in turn requires significant improvements to target selection for two reasons. First, the average silencing activity of randomly selected siRNAs is as low as 62%. Second, applying more than five different siRNAs may lead to saturation of the RNA-induced silencing complex (RISC) and to the degradation of untargeted genes. Therefore, selecting a small number of highly active siRNAs is critical for maximizing knockdown and minimizing off-target effects. To satisfy these needs, a publicly available and transparent machine learning tool is presented that ranks all possible siRNAs for each targeted gene. Support vector machines (SVMs) with polynomial kernels and constrained optimization models select and utilize the most predictive effective combinations from 572 sequence, thermodynamic, accessibility and self-hairpin features over 2200 published siRNAs. This tool reaches an accuracy of 92.3% in cross-validation experiments. We fully present the underlying biophysical signature that involves free energy, accessibility and dinucleotide characteristics. We show that while complete silencing is possible at certain structured target sites, accessibility information improves the prediction of the 90% active siRNA target sites. Fast siRNA activity predictions can be performed on our web server at
Url:
DOI: 10.1093/nar/gkl1065
PubMed: 17169992
PubMed Central: 1802606
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<front><div type="abstract" xml:lang="en"><p>Highly accurate knockdown functional analyses based on RNA interference (RNAi) require the possible most complete hydrolysis of the targeted mRNA while avoiding the degradation of untargeted genes (off-target effects). This in turn requires significant improvements to target selection for two reasons. First, the average silencing activity of randomly selected siRNAs is as low as 62%. Second, applying more than five different siRNAs may lead to saturation of the RNA-induced silencing complex (RISC) and to the degradation of untargeted genes. Therefore, selecting a small number of highly active siRNAs is critical for maximizing knockdown and minimizing off-target effects. To satisfy these needs, a publicly available and transparent machine learning tool is presented that ranks all possible siRNAs for each targeted gene. Support vector machines (SVMs) with polynomial kernels and constrained optimization models select and utilize the most predictive effective combinations from 572 sequence, thermodynamic, accessibility and self-hairpin features over 2200 published siRNAs. This tool reaches an accuracy of 92.3% in cross-validation experiments. We fully present the underlying biophysical signature that involves free energy, accessibility and dinucleotide characteristics. We show that while complete silencing is possible at certain structured target sites, accessibility information improves the prediction of the 90% active siRNA target sites. Fast siRNA activity predictions can be performed on our web server at <ext-link ext-link-type="uri" xlink:href="http://optirna.unl.edu/"></ext-link>
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<back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Huesken, D" uniqKey="Huesken D">D. Huesken</name>
</author>
<author><name sortKey="Lange, J" uniqKey="Lange J">J. Lange</name>
</author>
<author><name sortKey="Mickanin, C" uniqKey="Mickanin C">C. Mickanin</name>
</author>
<author><name sortKey="Weiler, J" uniqKey="Weiler J">J. Weiler</name>
</author>
<author><name sortKey="Asselbergs, F" uniqKey="Asselbergs F">F. Asselbergs</name>
</author>
<author><name sortKey="Warner, J" uniqKey="Warner J">J. Warner</name>
</author>
<author><name sortKey="Meloon, B" uniqKey="Meloon B">B. Meloon</name>
</author>
<author><name sortKey="Engel, S" uniqKey="Engel S">S. Engel</name>
</author>
<author><name sortKey="Rosenberg, A" uniqKey="Rosenberg A">A. Rosenberg</name>
</author>
<author><name sortKey="Cohen, D" uniqKey="Cohen D">D. Cohen</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Elbashir, S M" uniqKey="Elbashir S">S.M. Elbashir</name>
</author>
<author><name sortKey="Martinez, J" uniqKey="Martinez J">J. Martinez</name>
</author>
<author><name sortKey="Patkaniowska, A" uniqKey="Patkaniowska A">A. Patkaniowska</name>
</author>
<author><name sortKey="Lendeckel, W" uniqKey="Lendeckel W">W. Lendeckel</name>
</author>
<author><name sortKey="Tuschl, T" uniqKey="Tuschl T">T. Tuschl</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Reynolds, A" uniqKey="Reynolds A">A. Reynolds</name>
</author>
<author><name sortKey="Leake, D" uniqKey="Leake D">D. Leake</name>
</author>
<author><name sortKey="Boese, Q" uniqKey="Boese Q">Q. Boese</name>
</author>
<author><name sortKey="Scaringe, S" uniqKey="Scaringe S">S. Scaringe</name>
</author>
<author><name sortKey="Marshall, W S" uniqKey="Marshall W">W.S. Marshall</name>
</author>
<author><name sortKey="Khvorova, A" uniqKey="Khvorova A">A. Khvorova</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Yuan, B" uniqKey="Yuan B">B. Yuan</name>
</author>
<author><name sortKey="Latek, R" uniqKey="Latek R">R. Latek</name>
</author>
<author><name sortKey="Hossbach, M" uniqKey="Hossbach M">M. Hossbach</name>
</author>
<author><name sortKey="Tuschl, T" uniqKey="Tuschl T">T. Tuschl</name>
</author>
<author><name sortKey="Lewitter, F" uniqKey="Lewitter F">F. Lewitter</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Ui Tei, K" uniqKey="Ui Tei K">K. Ui-Tei</name>
</author>
<author><name sortKey="Naito, Y" uniqKey="Naito Y">Y. Naito</name>
</author>
<author><name sortKey="Takahashi, F" uniqKey="Takahashi F">F. Takahashi</name>
</author>
<author><name sortKey="Haraguchi, T" uniqKey="Haraguchi T">T. Haraguchi</name>
</author>
<author><name sortKey="Ohki Hamazaki, H" uniqKey="Ohki Hamazaki H">H. Ohki-Hamazaki</name>
</author>
<author><name sortKey="Juni, A" uniqKey="Juni A">A. Juni</name>
</author>
<author><name sortKey="Ueda, R" uniqKey="Ueda R">R. Ueda</name>
</author>
<author><name sortKey="Saigo, K" uniqKey="Saigo K">K. Saigo</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Amarzguioui, M" uniqKey="Amarzguioui M">M. Amarzguioui</name>
</author>
<author><name sortKey="Prydz, H" uniqKey="Prydz H">H. Prydz</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Khvorova, A" uniqKey="Khvorova A">A. Khvorova</name>
</author>
<author><name sortKey="Reynolds, A" uniqKey="Reynolds A">A. Reynolds</name>
</author>
<author><name sortKey="Jayasena, S D" uniqKey="Jayasena S">S.D. Jayasena</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Lee, N S" uniqKey="Lee N">N.S. Lee</name>
</author>
<author><name sortKey="Dohjima, T" uniqKey="Dohjima T">T. Dohjima</name>
</author>
<author><name sortKey="Bauer, G" uniqKey="Bauer G">G. Bauer</name>
</author>
<author><name sortKey="Li, H" uniqKey="Li H">H. Li</name>
</author>
<author><name sortKey="Li, M J" uniqKey="Li M">M.J. Li</name>
</author>
<author><name sortKey="Ehsani, A" uniqKey="Ehsani A">A. Ehsani</name>
</author>
<author><name sortKey="Salvaterra, P" uniqKey="Salvaterra P">P. Salvaterra</name>
</author>
<author><name sortKey="Rossi, J" uniqKey="Rossi J">J. Rossi</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Bohula, E A" uniqKey="Bohula E">E.A. Bohula</name>
</author>
<author><name sortKey="Salisbury, A J" uniqKey="Salisbury A">A.J. Salisbury</name>
</author>
<author><name sortKey="Sohail, M" uniqKey="Sohail M">M. Sohail</name>
</author>
<author><name sortKey="Playford, M P" uniqKey="Playford M">M.P. Playford</name>
</author>
<author><name sortKey="Riedemann, J" uniqKey="Riedemann J">J. Riedemann</name>
</author>
<author><name sortKey="Southern, E M" uniqKey="Southern E">E.M. Southern</name>
</author>
<author><name sortKey="Macaulay, V M" uniqKey="Macaulay V">V.M. Macaulay</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Kretschmer Kazemi Far, R" uniqKey="Kretschmer Kazemi Far R">R. Kretschmer-Kazemi Far</name>
</author>
<author><name sortKey="Sczakiel, G" uniqKey="Sczakiel G">G. Sczakiel</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Scholkopf, B" uniqKey="Scholkopf B">B. Schölkopf</name>
</author>
<author><name sortKey="Smola, A J" uniqKey="Smola A">A.J. Smola</name>
</author>
<author><name sortKey="Williamson, R C" uniqKey="Williamson R">R.C. Williamson</name>
</author>
<author><name sortKey="Bartlett, P L" uniqKey="Bartlett P">P.L. Bartlett</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Camps Valls, G" uniqKey="Camps Valls G">G. Camps-Valls</name>
</author>
<author><name sortKey="Chalk, A M" uniqKey="Chalk A">A.M. Chalk</name>
</author>
<author><name sortKey="Serrano Lopez, A J" uniqKey="Serrano Lopez A">A.J. Serrano-Lopez</name>
</author>
<author><name sortKey="Martin Guerrero, J D" uniqKey="Martin Guerrero J">J.D. Martin-Guerrero</name>
</author>
<author><name sortKey="Sonnhammer, E L" uniqKey="Sonnhammer E">E.L. Sonnhammer</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="S Trom, P" uniqKey="S Trom P">P. Sætrom</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Shabalina, S A" uniqKey="Shabalina S">S.A. Shabalina</name>
</author>
<author><name sortKey="Spiridonov, A N" uniqKey="Spiridonov A">A.N. Spiridonov</name>
</author>
<author><name sortKey="Ogurtsov, A Y" uniqKey="Ogurtsov A">A.Y. Ogurtsov</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Holen, T" uniqKey="Holen T">T. Holen</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Chalk, A M" uniqKey="Chalk A">A.M. Chalk</name>
</author>
<author><name sortKey="Wahlestedt, C" uniqKey="Wahlestedt C">C. Wahlestedt</name>
</author>
<author><name sortKey="Sonnhammer, E L" uniqKey="Sonnhammer E">E.L. Sonnhammer</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="S Trom, P" uniqKey="S Trom P">P. Sætrom</name>
</author>
<author><name sortKey="Snove, J O" uniqKey="Snove J">J.O. Snove</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Xia, T" uniqKey="Xia T">T. Xia</name>
</author>
<author><name sortKey="Santalucia, J" uniqKey="Santalucia J">J., SantaLucia</name>
</author>
<author><name sortKey="Burkard, M E" uniqKey="Burkard M">M.E. Burkard</name>
</author>
<author><name sortKey="Kierzek, R" uniqKey="Kierzek R">R. Kierzek</name>
</author>
<author><name sortKey="Schroeder, S J" uniqKey="Schroeder S">S.J. Schroeder</name>
</author>
<author><name sortKey="Jiao, X" uniqKey="Jiao X">X. Jiao</name>
</author>
<author><name sortKey="Cox, C" uniqKey="Cox C">C. Cox</name>
</author>
<author><name sortKey="Turner, D H" uniqKey="Turner D">D.H. Turner</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Muckstein, U" uniqKey="Muckstein U">U. Muckstein</name>
</author>
<author><name sortKey="Tafer, H" uniqKey="Tafer H">H. Tafer</name>
</author>
<author><name sortKey="Hackermuller, J" uniqKey="Hackermuller J">J. Hackermuller</name>
</author>
<author><name sortKey="Bernhart, S H" uniqKey="Bernhart S">S.H. Bernhart</name>
</author>
<author><name sortKey="Stadler, P F" uniqKey="Stadler P">P.F. Stadler</name>
</author>
<author><name sortKey="Hofacker, I L" uniqKey="Hofacker I">I.L. Hofacker</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Ding, Y" uniqKey="Ding Y">Y. Ding</name>
</author>
<author><name sortKey="Lawrence, C E" uniqKey="Lawrence C">C.E. Lawrence</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Ding, Y" uniqKey="Ding Y">Y. Ding</name>
</author>
<author><name sortKey="Lawrence, C E" uniqKey="Lawrence C">C.E. Lawrence</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Ding, Y" uniqKey="Ding Y">Y. Ding</name>
</author>
<author><name sortKey="Lawrence, C E" uniqKey="Lawrence C">C.E. Lawrence</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Dantzig, G B" uniqKey="Dantzig G">G.B. Dantzig</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Goldfarb, D" uniqKey="Goldfarb D">D. Goldfarb</name>
</author>
<author><name sortKey="Todd, M" uniqKey="Todd M">M. Todd</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Scholkopf, B" uniqKey="Scholkopf B">B. Schölkopf</name>
</author>
<author><name sortKey="Smola, A J" uniqKey="Smola A">A.J. Smola</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Tsang, I W" uniqKey="Tsang I">I.W. Tsang</name>
</author>
<author><name sortKey="Kwok, J T" uniqKey="Kwok J">J.T. Kwok</name>
</author>
<author><name sortKey="Cheung, P M" uniqKey="Cheung P">P.-M. Cheung</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Joachims, T" uniqKey="Joachims T">T. Joachims</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Ladunga, I" uniqKey="Ladunga I">I. Ladunga</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Bennett, K" uniqKey="Bennett K">K. Bennett</name>
</author>
<author><name sortKey="Mangasarian, O L" uniqKey="Mangasarian O">O.L. Mangasarian</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Chvatal, V" uniqKey="Chvatal V">V. Chvàtal</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Huber, P J" uniqKey="Huber P">P.J. Huber</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Kohavi, R" uniqKey="Kohavi R">R. Kohavi</name>
</author>
<author><name sortKey="John, G H" uniqKey="John G">G.H. John</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Guyon, I" uniqKey="Guyon I">I. Guyon</name>
</author>
<author><name sortKey="Weston, J" uniqKey="Weston J">J. Weston</name>
</author>
<author><name sortKey="Barnhill, S" uniqKey="Barnhill S">S. Barnhill</name>
</author>
<author><name sortKey="Vapnik, V" uniqKey="Vapnik V">V. Vapnik</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Furlanello, C" uniqKey="Furlanello C">C. Furlanello</name>
</author>
<author><name sortKey="Serafini, M" uniqKey="Serafini M">M. Serafini</name>
</author>
<author><name sortKey="Merler, S" uniqKey="Merler S">S. Merler</name>
</author>
<author><name sortKey="Jurman, G" uniqKey="Jurman G">G. Jurman</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Block, P" uniqKey="Block P">P. Block</name>
</author>
<author><name sortKey="Paern, J" uniqKey="Paern J">J. Paern</name>
</author>
<author><name sortKey="Hullermeier, E" uniqKey="Hullermeier E">E. Hullermeier</name>
</author>
<author><name sortKey="Sanschagrin, P" uniqKey="Sanschagrin P">P. Sanschagrin</name>
</author>
<author><name sortKey="Sotriffer, C A" uniqKey="Sotriffer C">C.A. Sotriffer</name>
</author>
<author><name sortKey="Klebe, G" uniqKey="Klebe G">G. Klebe</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Hoffmann, R" uniqKey="Hoffmann R">R. Hoffmann</name>
</author>
<author><name sortKey="Valencia, A" uniqKey="Valencia A">A. Valencia</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Mladenic, D" uniqKey="Mladenic D">D. Mladenic</name>
</author>
<author><name sortKey="Brank, J" uniqKey="Brank J">J. Brank</name>
</author>
<author><name sortKey="Grobelnik, M" uniqKey="Grobelnik M">M. Grobelnik</name>
</author>
<author><name sortKey="Milic Frayling, N" uniqKey="Milic Frayling N">N. Milic-Frayling</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Joachims, T" uniqKey="Joachims T">T. Joachims</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Le Cun, Y" uniqKey="Le Cun Y">Y. Le Cun</name>
</author>
<author><name sortKey="Denker, J S" uniqKey="Denker J">J.S. Denker</name>
</author>
<author><name sortKey="Solla, S A" uniqKey="Solla S">S.A. Solla</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Boese, Q" uniqKey="Boese Q">Q. Boese</name>
</author>
<author><name sortKey="Leake, D" uniqKey="Leake D">D. Leake</name>
</author>
<author><name sortKey="Reynolds, A" uniqKey="Reynolds A">A. Reynolds</name>
</author>
<author><name sortKey="Read, S" uniqKey="Read S">S. Read</name>
</author>
<author><name sortKey="Scaringe, S A" uniqKey="Scaringe S">S.A. Scaringe</name>
</author>
<author><name sortKey="Marshall, W S" uniqKey="Marshall W">W.S. Marshall</name>
</author>
<author><name sortKey="Khvorova, A" uniqKey="Khvorova A">A. Khvorova</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Mathews, D H" uniqKey="Mathews D">D.H. Mathews</name>
</author>
<author><name sortKey="Turner, D H" uniqKey="Turner D">D.H. Turner</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Eisenfeld, J" uniqKey="Eisenfeld J">J. Eisenfeld</name>
</author>
<author><name sortKey="Vajda, S" uniqKey="Vajda S">S. Vajda</name>
</author>
<author><name sortKey="Sugar, I" uniqKey="Sugar I">I. Sugar</name>
</author>
<author><name sortKey="Delisi, C" uniqKey="Delisi C">C. DeLisi</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Matranga, C" uniqKey="Matranga C">C. Matranga</name>
</author>
<author><name sortKey="Tomari, Y" uniqKey="Tomari Y">Y. Tomari</name>
</author>
<author><name sortKey="Shin, C" uniqKey="Shin C">C. Shin</name>
</author>
<author><name sortKey="Bartel, D P" uniqKey="Bartel D">D.P. Bartel</name>
</author>
<author><name sortKey="Zamore, P D" uniqKey="Zamore P">P.D. Zamore</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Far, R K" uniqKey="Far R">R.K. Far</name>
</author>
<author><name sortKey="Nedbal, W" uniqKey="Nedbal W">W. Nedbal</name>
</author>
<author><name sortKey="Sczakiel, G" uniqKey="Sczakiel G">G. Sczakiel</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Patzel, V" uniqKey="Patzel V">V. Patzel</name>
</author>
<author><name sortKey="Rutz, S" uniqKey="Rutz S">S. Rutz</name>
</author>
<author><name sortKey="Dietrich, I" uniqKey="Dietrich I">I. Dietrich</name>
</author>
<author><name sortKey="Koberle, C" uniqKey="Koberle C">C. Koberle</name>
</author>
<author><name sortKey="Scheffold, A" uniqKey="Scheffold A">A. Scheffold</name>
</author>
<author><name sortKey="Kaufmann, S H E" uniqKey="Kaufmann S">S.H.E. Kaufmann</name>
</author>
</analytic>
</biblStruct>
</listBibl>
</div1>
</back>
</TEI>
<pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Nucleic Acids Res</journal-id>
<journal-id journal-id-type="iso-abbrev">Nucleic Acids Res</journal-id>
<journal-id journal-id-type="pmc">nar</journal-id>
<journal-id journal-id-type="publisher-id">Nucleic Acids Research</journal-id>
<journal-title-group><journal-title>Nucleic Acids Research</journal-title>
</journal-title-group>
<issn pub-type="ppub">0305-1048</issn>
<issn pub-type="epub">1362-4962</issn>
<publisher><publisher-name>Oxford University Press</publisher-name>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">17169992</article-id>
<article-id pub-id-type="pmc">1802606</article-id>
<article-id pub-id-type="doi">10.1093/nar/gkl1065</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Computational Biology</subject>
</subj-group>
</article-categories>
<title-group><article-title>More complete gene silencing by fewer siRNAs: transparent optimized design and biophysical signature</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Ladunga</surname>
<given-names>Istvan</given-names>
</name>
<xref ref-type="corresp" rid="cor1">*</xref>
</contrib>
<aff><institution>Center for Biotechnology and Department of Statistics, University of Nebraska–Lincoln</institution>
<addr-line>Lincoln, NE 68588-0665, USA</addr-line>
</aff>
</contrib-group>
<author-notes><corresp id="cor1"><sup>*</sup>
Tel: +1 402 472 6074; Email: <email>sladunga@unl.edu</email>
</corresp>
</author-notes>
<pub-date pub-type="ppub"><month>1</month>
<year>2007</year>
</pub-date>
<pub-date pub-type="epub"><day>14</day>
<month>12</month>
<year>2006</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>14</day>
<month>12</month>
<year>2006</year>
</pub-date>
<pmc-comment> PMC Release delay is 0 months and 0 days and was based on the
. </pmc-comment>
<volume>35</volume>
<issue>2</issue>
<fpage>433</fpage>
<lpage>440</lpage>
<history><date date-type="received"><day>05</day>
<month>10</month>
<year>2006</year>
</date>
<date date-type="rev-recd"><day>14</day>
<month>11</month>
<year>2006</year>
</date>
<date date-type="accepted"><day>20</day>
<month>11</month>
<year>2006</year>
</date>
</history>
<permissions><copyright-statement>© 2006 The Author(s).</copyright-statement>
<copyright-year>2006</copyright-year>
<license license-type="openaccess"><license-p><pmc-comment>CREATIVE COMMONS</pmc-comment>
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by-nc/2.0/uk/">http://creativecommons.org/licenses/by-nc/2.0/uk/</ext-link>
) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
</license>
</permissions>
<abstract><p>Highly accurate knockdown functional analyses based on RNA interference (RNAi) require the possible most complete hydrolysis of the targeted mRNA while avoiding the degradation of untargeted genes (off-target effects). This in turn requires significant improvements to target selection for two reasons. First, the average silencing activity of randomly selected siRNAs is as low as 62%. Second, applying more than five different siRNAs may lead to saturation of the RNA-induced silencing complex (RISC) and to the degradation of untargeted genes. Therefore, selecting a small number of highly active siRNAs is critical for maximizing knockdown and minimizing off-target effects. To satisfy these needs, a publicly available and transparent machine learning tool is presented that ranks all possible siRNAs for each targeted gene. Support vector machines (SVMs) with polynomial kernels and constrained optimization models select and utilize the most predictive effective combinations from 572 sequence, thermodynamic, accessibility and self-hairpin features over 2200 published siRNAs. This tool reaches an accuracy of 92.3% in cross-validation experiments. We fully present the underlying biophysical signature that involves free energy, accessibility and dinucleotide characteristics. We show that while complete silencing is possible at certain structured target sites, accessibility information improves the prediction of the 90% active siRNA target sites. Fast siRNA activity predictions can be performed on our web server at <ext-link ext-link-type="uri" xlink:href="http://optirna.unl.edu/"></ext-link>
.</p>
</abstract>
</article-meta>
</front>
</pmc>
<affiliations><list></list>
<tree><noCountry><name sortKey="Ladunga, Istvan" sort="Ladunga, Istvan" uniqKey="Ladunga I" first="Istvan" last="Ladunga">Istvan Ladunga</name>
</noCountry>
</tree>
</affiliations>
</record>
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