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A comparative analysis of transcription factor binding models learned from PBM, HT-SELEX and ChIP data

Identifieur interne : 001145 ( Pmc/Checkpoint ); précédent : 001144; suivant : 001146

A comparative analysis of transcription factor binding models learned from PBM, HT-SELEX and ChIP data

Auteurs : Yaron Orenstein ; Ron Shamir

Source :

RBID : PMC:4005680

Abstract

Understanding gene regulation is a key challenge in today's biology. The new technologies of protein-binding microarrays (PBMs) and high-throughput SELEX (HT-SELEX) allow measurement of the binding intensities of one transcription factor (TF) to numerous synthetic double-stranded DNA sequences in a single experiment. Recently, Jolma et al. reported the results of 547 HT-SELEX experiments covering human and mouse TFs. Because 162 of these TFs were also covered by PBM technology, for the first time, a large-scale comparison between implementations of these two in vitro technologies is possible. Here we assessed the similarities and differences between binding models, represented as position weight matrices, inferred from PBM and HT-SELEX, and also measured how well these models predict in vivo binding. Our results show that HT-SELEX- and PBM-derived models agree for most TFs. For some TFs, the HT-SELEX-derived models are longer versions of the PBM-derived models, whereas for other TFs, the HT-SELEX models match the secondary PBM-derived models. Remarkably, PBM-based 8-mer ranking is more accurate than that of HT-SELEX, but models derived from HT-SELEX predict in vivo binding better. In addition, we reveal several biases in HT-SELEX data including nucleotide frequency bias, enrichment of C-rich k-mers and oligos and underrepresentation of palindromes.


Url:
DOI: 10.1093/nar/gku117
PubMed: 24500199
PubMed Central: 4005680


Affiliations:


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PMC:4005680

Le document en format XML

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<p>Understanding gene regulation is a key challenge in today's biology. The new technologies of protein-binding microarrays (PBMs) and high-throughput SELEX (HT-SELEX) allow measurement of the binding intensities of one transcription factor (TF) to numerous synthetic double-stranded DNA sequences in a single experiment. Recently, Jolma
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reported the results of 547 HT-SELEX experiments covering human and mouse TFs. Because 162 of these TFs were also covered by PBM technology, for the first time, a large-scale comparison between implementations of these two
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technologies is possible. Here we assessed the similarities and differences between binding models, represented as position weight matrices, inferred from PBM and HT-SELEX, and also measured how well these models predict
<italic>in vivo</italic>
binding. Our results show that HT-SELEX- and PBM-derived models agree for most TFs. For some TFs, the HT-SELEX-derived models are longer versions of the PBM-derived models, whereas for other TFs, the HT-SELEX models match the secondary PBM-derived models. Remarkably, PBM-based 8-mer ranking is more accurate than that of HT-SELEX, but models derived from HT-SELEX predict
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<name sortKey="Shen, N" uniqKey="Shen N">N Shen</name>
</author>
<author>
<name sortKey="Dror, I" uniqKey="Dror I">I Dror</name>
</author>
<author>
<name sortKey="Zhou, T" uniqKey="Zhou T">T Zhou</name>
</author>
<author>
<name sortKey="Horton, J" uniqKey="Horton J">J Horton</name>
</author>
<author>
<name sortKey="Rohs, R" uniqKey="Rohs R">R Rohs</name>
</author>
<author>
<name sortKey="Bulyk, Ml" uniqKey="Bulyk M">ML Bulyk</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Yang, L" uniqKey="Yang L">L Yang</name>
</author>
<author>
<name sortKey="Zhou, T" uniqKey="Zhou T">T Zhou</name>
</author>
<author>
<name sortKey="Dror, I" uniqKey="Dror I">I Dror</name>
</author>
<author>
<name sortKey="Mathelier, A" uniqKey="Mathelier A">A Mathelier</name>
</author>
<author>
<name sortKey="Wasserman, Ww" uniqKey="Wasserman W">WW Wasserman</name>
</author>
<author>
<name sortKey="Gordan, R" uniqKey="Gordan R">R Gordan</name>
</author>
<author>
<name sortKey="Rohs, R" uniqKey="Rohs R">R Rohs</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="publisher-id">nar</journal-id>
<journal-id journal-id-type="hwp">nar</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">24500199</article-id>
<article-id pub-id-type="pmc">4005680</article-id>
<article-id pub-id-type="doi">10.1093/nar/gku117</article-id>
<article-id pub-id-type="publisher-id">gku117</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Methods Online</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>A comparative analysis of transcription factor binding models learned from PBM, HT-SELEX and ChIP data</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Orenstein</surname>
<given-names>Yaron</given-names>
</name>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Shamir</surname>
<given-names>Ron</given-names>
</name>
<xref ref-type="corresp" rid="gku117-COR1">*</xref>
</contrib>
<aff>Blavatnik School of Computer Science, Tel-Aviv University, Tel Aviv 69978, Israel</aff>
</contrib-group>
<author-notes>
<corresp id="gku117-COR1">*To whom correspondence should be addressed. Tel:
<phone>+972 3 6405383</phone>
; Fax:
<fax>+972 3 640 5384</fax>
; Email:
<email>rshamir@tau.ac.il</email>
</corresp>
<fn>
<p>Present address: Ron Shamir, School of Computer Science, Tel-Aviv University, P.O.B. 39040, Tel-Aviv 69978, Israel.</p>
</fn>
</author-notes>
<pub-date pub-type="ppub">
<month>4</month>
<year>2014</year>
</pub-date>
<pub-date pub-type="epub">
<day>5</day>
<month>2</month>
<year>2014</year>
</pub-date>
<pub-date pub-type="pmc-release">
<day>5</day>
<month>2</month>
<year>2014</year>
</pub-date>
<pmc-comment> PMC Release delay is 0 months and 0 days and was based on the . </pmc-comment>
<volume>42</volume>
<issue>8</issue>
<fpage>e63</fpage>
<lpage>e63</lpage>
<history>
<date date-type="received">
<day>11</day>
<month>11</month>
<year>2013</year>
</date>
<date date-type="rev-recd">
<day>22</day>
<month>12</month>
<year>2013</year>
</date>
<date date-type="accepted">
<day>16</day>
<month>1</month>
<year>2014</year>
</date>
</history>
<permissions>
<copyright-statement>© The Author(s) 2014. Published by Oxford University Press.</copyright-statement>
<copyright-year>2014</copyright-year>
<license license-type="creative-commons" xlink:href="http://creativecommons.org/licenses/by/3.0/">
<license-p>
<pmc-comment>CREATIVE COMMONS</pmc-comment>
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (
<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/3.0/">http://creativecommons.org/licenses/by/3.0/</ext-link>
), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
</license>
</permissions>
<abstract>
<p>Understanding gene regulation is a key challenge in today's biology. The new technologies of protein-binding microarrays (PBMs) and high-throughput SELEX (HT-SELEX) allow measurement of the binding intensities of one transcription factor (TF) to numerous synthetic double-stranded DNA sequences in a single experiment. Recently, Jolma
<italic>et al.</italic>
reported the results of 547 HT-SELEX experiments covering human and mouse TFs. Because 162 of these TFs were also covered by PBM technology, for the first time, a large-scale comparison between implementations of these two
<italic>in vitro</italic>
technologies is possible. Here we assessed the similarities and differences between binding models, represented as position weight matrices, inferred from PBM and HT-SELEX, and also measured how well these models predict
<italic>in vivo</italic>
binding. Our results show that HT-SELEX- and PBM-derived models agree for most TFs. For some TFs, the HT-SELEX-derived models are longer versions of the PBM-derived models, whereas for other TFs, the HT-SELEX models match the secondary PBM-derived models. Remarkably, PBM-based 8-mer ranking is more accurate than that of HT-SELEX, but models derived from HT-SELEX predict
<italic>in vivo</italic>
binding better. In addition, we reveal several biases in HT-SELEX data including nucleotide frequency bias, enrichment of C-rich k-mers and oligos and underrepresentation of palindromes.</p>
</abstract>
<counts>
<page-count count="10"></page-count>
</counts>
</article-meta>
</front>
</pmc>
<affiliations>
<list></list>
<tree>
<noCountry>
<name sortKey="Orenstein, Yaron" sort="Orenstein, Yaron" uniqKey="Orenstein Y" first="Yaron" last="Orenstein">Yaron Orenstein</name>
<name sortKey="Shamir, Ron" sort="Shamir, Ron" uniqKey="Shamir R" first="Ron" last="Shamir">Ron Shamir</name>
</noCountry>
</tree>
</affiliations>
</record>

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