Functional characterization of transcription factor motifs using cross-species comparison across large evolutionary distances.

We address the problem of finding statistically significant associations between cis-regulatory motifs and functional gene sets, in order to understand the biological roles of transcription factors. We develop a computational framework for this task, whose features include a new statistical score fo...

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Main Authors: Jaebum Kim, Ryan Cunningham, Brian James, Stefan Wyder, Joshua D Gibson, Oliver Niehuis, Evgeny M Zdobnov, Hugh M Robertson, Gene E Robinson, John H Werren, Saurabh Sinha
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2010-01-01
Series:PLoS Computational Biology
Online Access:https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1000652&type=printable
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author Jaebum Kim
Ryan Cunningham
Brian James
Stefan Wyder
Joshua D Gibson
Oliver Niehuis
Evgeny M Zdobnov
Hugh M Robertson
Gene E Robinson
John H Werren
Saurabh Sinha
author_facet Jaebum Kim
Ryan Cunningham
Brian James
Stefan Wyder
Joshua D Gibson
Oliver Niehuis
Evgeny M Zdobnov
Hugh M Robertson
Gene E Robinson
John H Werren
Saurabh Sinha
author_sort Jaebum Kim
collection DOAJ
description We address the problem of finding statistically significant associations between cis-regulatory motifs and functional gene sets, in order to understand the biological roles of transcription factors. We develop a computational framework for this task, whose features include a new statistical score for motif scanning, the use of different scores for predicting targets of different motifs, and new ways to deal with redundancies among significant motif-function associations. This framework is applied to the recently sequenced genome of the jewel wasp, Nasonia vitripennis, making use of the existing knowledge of motifs and gene annotations in another insect genome, that of the fruitfly. The framework uses cross-species comparison to improve the specificity of its predictions, and does so without relying upon non-coding sequence alignment. It is therefore well suited for comparative genomics across large evolutionary divergences, where existing alignment-based methods are not applicable. We also apply the framework to find motifs associated with socially regulated gene sets in the honeybee, Apis mellifera, using comparisons with Nasonia, a solitary species, to identify honeybee-specific associations.
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publishDate 2010-01-01
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spelling doaj-art-8785e2bc96b541cd9a93034296c8fa322025-08-20T03:19:50ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582010-01-0161e100065210.1371/journal.pcbi.1000652Functional characterization of transcription factor motifs using cross-species comparison across large evolutionary distances.Jaebum KimRyan CunninghamBrian JamesStefan WyderJoshua D GibsonOliver NiehuisEvgeny M ZdobnovHugh M RobertsonGene E RobinsonJohn H WerrenSaurabh SinhaWe address the problem of finding statistically significant associations between cis-regulatory motifs and functional gene sets, in order to understand the biological roles of transcription factors. We develop a computational framework for this task, whose features include a new statistical score for motif scanning, the use of different scores for predicting targets of different motifs, and new ways to deal with redundancies among significant motif-function associations. This framework is applied to the recently sequenced genome of the jewel wasp, Nasonia vitripennis, making use of the existing knowledge of motifs and gene annotations in another insect genome, that of the fruitfly. The framework uses cross-species comparison to improve the specificity of its predictions, and does so without relying upon non-coding sequence alignment. It is therefore well suited for comparative genomics across large evolutionary divergences, where existing alignment-based methods are not applicable. We also apply the framework to find motifs associated with socially regulated gene sets in the honeybee, Apis mellifera, using comparisons with Nasonia, a solitary species, to identify honeybee-specific associations.https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1000652&type=printable
spellingShingle Jaebum Kim
Ryan Cunningham
Brian James
Stefan Wyder
Joshua D Gibson
Oliver Niehuis
Evgeny M Zdobnov
Hugh M Robertson
Gene E Robinson
John H Werren
Saurabh Sinha
Functional characterization of transcription factor motifs using cross-species comparison across large evolutionary distances.
PLoS Computational Biology
title Functional characterization of transcription factor motifs using cross-species comparison across large evolutionary distances.
title_full Functional characterization of transcription factor motifs using cross-species comparison across large evolutionary distances.
title_fullStr Functional characterization of transcription factor motifs using cross-species comparison across large evolutionary distances.
title_full_unstemmed Functional characterization of transcription factor motifs using cross-species comparison across large evolutionary distances.
title_short Functional characterization of transcription factor motifs using cross-species comparison across large evolutionary distances.
title_sort functional characterization of transcription factor motifs using cross species comparison across large evolutionary distances
url https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1000652&type=printable
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