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Predicting the binding preference of transcription factors to individual DNA k-mers

Identifieur interne : 000938 ( Pmc/Curation ); précédent : 000937; suivant : 000939

Predicting the binding preference of transcription factors to individual DNA k-mers

Auteurs : Trevis M. Alleyne ; Lourdes Pe A-Castillo [Canada] ; Gwenael Badis [Canada] ; Shaheynoor Talukder ; Michael F. Berger [États-Unis] ; Andrew R. Gehrke [États-Unis] ; Anthony A. Philippakis [États-Unis] ; Martha L. Bulyk [États-Unis] ; Quaid D. Morris [Canada] ; Timothy R. Hughes [Canada]

Source :

RBID : PMC:2666811

Abstract

Motivation: Recognition of specific DNA sequences is a central mechanism by which transcription factors (TFs) control gene expression. Many TF-binding preferences, however, are unknown or poorly characterized, in part due to the difficulty associated with determining their specificity experimentally, and an incomplete understanding of the mechanisms governing sequence specificity. New techniques that estimate the affinity of TFs to all possible k-mers provide a new opportunity to study DNA–protein interaction mechanisms, and may facilitate inference of binding preferences for members of a given TF family when such information is available for other family members.

Results: We employed a new dataset consisting of the relative preferences of mouse homeodomains for all eight-base DNA sequences in order to ask how well we can predict the binding profiles of homeodomains when only their protein sequences are given. We evaluated a panel of standard statistical inference techniques, as well as variations of the protein features considered. Nearest neighbour among functionally important residues emerged among the most effective methods. Our results underscore the complexity of TF–DNA recognition, and suggest a rational approach for future analyses of TF families.

Contact: t.hughes@utorotno.ca

Supplementary information: Supplementary data are available at Bioinformatics online.


Url:
DOI: 10.1093/bioinformatics/btn645
PubMed: 19088121
PubMed Central: 2666811

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PMC:2666811

Le document en format XML

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<bold>Motivation:</bold>
Recognition of specific DNA sequences is a central mechanism by which transcription factors (TFs) control gene expression. Many TF-binding preferences, however, are unknown or poorly characterized, in part due to the difficulty associated with determining their specificity experimentally, and an incomplete understanding of the mechanisms governing sequence specificity. New techniques that estimate the affinity of TFs to all possible
<italic>k</italic>
-mers provide a new opportunity to study DNA–protein interaction mechanisms, and may facilitate inference of binding preferences for members of a given TF family when such information is available for other family members.</p>
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<bold>Results:</bold>
We employed a new dataset consisting of the relative preferences of mouse homeodomains for all eight-base DNA sequences in order to ask how well we can predict the binding profiles of homeodomains when only their protein sequences are given. We evaluated a panel of standard statistical inference techniques, as well as variations of the protein features considered. Nearest neighbour among functionally important residues emerged among the most effective methods. Our results underscore the complexity of TF–DNA recognition, and suggest a rational approach for future analyses of TF families.</p>
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<bold>Contact:</bold>
<email>t.hughes@utorotno.ca</email>
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<bold>Supplementary information:</bold>
<ext-link ext-link-type="uri" xlink:href="http://bioinformatics.oxfordjournals.org/cgi/content/full/btn645/DC1">Supplementary data</ext-link>
are available at
<italic>Bioinformatics</italic>
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<italic>k</italic>
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<name>
<surname>Alleyne</surname>
<given-names>Trevis M.</given-names>
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<sup>1</sup>
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<name>
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<given-names>Lourdes</given-names>
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<xref ref-type="aff" rid="AFF1">
<sup>2</sup>
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<given-names>Gwenael</given-names>
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<xref ref-type="aff" rid="AFF1">
<sup>2</sup>
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<name>
<surname>Talukder</surname>
<given-names>Shaheynoor</given-names>
</name>
<xref ref-type="aff" rid="AFF1">
<sup>1</sup>
</xref>
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<contrib contrib-type="author">
<name>
<surname>Berger</surname>
<given-names>Michael F.</given-names>
</name>
<xref ref-type="aff" rid="AFF1">
<sup>3</sup>
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<xref ref-type="aff" rid="AFF1">
<sup>4</sup>
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<given-names>Andrew R.</given-names>
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<given-names>Anthony A.</given-names>
</name>
<xref ref-type="aff" rid="AFF1">
<sup>3</sup>
</xref>
<xref ref-type="aff" rid="AFF1">
<sup>4</sup>
</xref>
<xref ref-type="aff" rid="AFF1">
<sup>5</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Bulyk</surname>
<given-names>Martha L.</given-names>
</name>
<xref ref-type="aff" rid="AFF1">
<sup>3</sup>
</xref>
<xref ref-type="aff" rid="AFF1">
<sup>4</sup>
</xref>
<xref ref-type="aff" rid="AFF1">
<sup>5</sup>
</xref>
<xref ref-type="aff" rid="AFF1">
<sup>6</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Morris</surname>
<given-names>Quaid D.</given-names>
</name>
<xref ref-type="aff" rid="AFF1">
<sup>1</sup>
</xref>
<xref ref-type="aff" rid="AFF1">
<sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Hughes</surname>
<given-names>Timothy R.</given-names>
</name>
<xref ref-type="aff" rid="AFF1">
<sup>1</sup>
</xref>
<xref ref-type="aff" rid="AFF1">
<sup>2</sup>
</xref>
<xref ref-type="corresp" rid="COR1">*</xref>
</contrib>
</contrib-group>
<aff id="AFF1">
<sup>1</sup>
Department of Molecular Genetics,
<sup>2</sup>
Banting and Best Department of Medical Research, University of Toronto, Toronto, ON M5S 3E1, Canada,
<sup>3</sup>
Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115,
<sup>4</sup>
Committee on Higher Degrees in Biophysics, Harvard University, Cambridge, MA 02138,
<sup>5</sup>
Harvard/MIT Division of Health Sciences and Technology (HST), Harvard Medical School, Boston, MA 02115 and
<sup>6</sup>
Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA</aff>
<author-notes>
<corresp id="COR1">*To whom correspondence should be addressed.</corresp>
<fn>
<p>Associate Editor: David Rocke</p>
</fn>
</author-notes>
<pub-date pub-type="ppub">
<day>15</day>
<month>4</month>
<year>2009</year>
</pub-date>
<pub-date pub-type="epub">
<day>16</day>
<month>12</month>
<year>2008</year>
</pub-date>
<pub-date pub-type="pmc-release">
<day>16</day>
<month>12</month>
<year>2008</year>
</pub-date>
<pmc-comment> PMC Release delay is 0 months and 0 days and was based on the . </pmc-comment>
<volume>25</volume>
<issue>8</issue>
<fpage>1012</fpage>
<lpage>1018</lpage>
<history>
<date date-type="received">
<day>10</day>
<month>8</month>
<year>2008</year>
</date>
<date date-type="rev-recd">
<day>16</day>
<month>11</month>
<year>2008</year>
</date>
<date date-type="accepted">
<day>11</day>
<month>12</month>
<year>2008</year>
</date>
</history>
<permissions>
<copyright-statement>© 2008 The Author(s)</copyright-statement>
<copyright-year>2008</copyright-year>
<license license-type="creative-commons" xlink:href="http://creativecommons.org/licenses/by-nc/2.0/uk/">
<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.</p>
</license>
</permissions>
<abstract>
<p>
<bold>Motivation:</bold>
Recognition of specific DNA sequences is a central mechanism by which transcription factors (TFs) control gene expression. Many TF-binding preferences, however, are unknown or poorly characterized, in part due to the difficulty associated with determining their specificity experimentally, and an incomplete understanding of the mechanisms governing sequence specificity. New techniques that estimate the affinity of TFs to all possible
<italic>k</italic>
-mers provide a new opportunity to study DNA–protein interaction mechanisms, and may facilitate inference of binding preferences for members of a given TF family when such information is available for other family members.</p>
<p>
<bold>Results:</bold>
We employed a new dataset consisting of the relative preferences of mouse homeodomains for all eight-base DNA sequences in order to ask how well we can predict the binding profiles of homeodomains when only their protein sequences are given. We evaluated a panel of standard statistical inference techniques, as well as variations of the protein features considered. Nearest neighbour among functionally important residues emerged among the most effective methods. Our results underscore the complexity of TF–DNA recognition, and suggest a rational approach for future analyses of TF families.</p>
<p>
<bold>Contact:</bold>
<email>t.hughes@utorotno.ca</email>
</p>
<p>
<bold>Supplementary information:</bold>
<ext-link ext-link-type="uri" xlink:href="http://bioinformatics.oxfordjournals.org/cgi/content/full/btn645/DC1">Supplementary data</ext-link>
are available at
<italic>Bioinformatics</italic>
online.</p>
</abstract>
</article-meta>
</front>
</pmc>
</record>

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