Transcriptional programs: Modelling higher order structure in transcriptional control
<p>Abstract</p> <p>Background</p> <p>Transcriptional regulation is an important part of regulatory control in eukaryotes. Even if binding motifs for transcription factors are known, the task of finding binding sites by scanning sequences is plagued by false positives. O...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2009-07-01
|
| Series: | BMC Bioinformatics |
| Online Access: | http://www.biomedcentral.com/1471-2105/10/218 |
| _version_ | 1818565460519550976 |
|---|---|
| author | Wernisch Lorenz Ott Sascha Reid John E |
| author_facet | Wernisch Lorenz Ott Sascha Reid John E |
| author_sort | Wernisch Lorenz |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Transcriptional regulation is an important part of regulatory control in eukaryotes. Even if binding motifs for transcription factors are known, the task of finding binding sites by scanning sequences is plagued by false positives. One way to improve the detection of binding sites from motifs is by taking cooperativity of transcription factor binding into account. We propose a non-parametric probabilistic model, similar to a document topic model, for detecting <it>transcriptional programs</it>, groups of cooperative transcription factors and co-regulated genes. The analysis results in transcriptional programs which generalise both transcriptional modules and TF-target gene incidence matrices and provide a higher-level summary of these structures. The method is independent of prior specification of training sets of genes, for example, via gene expression data. The analysis is based on known binding motifs.</p> <p>Results</p> <p>We applied our method to putative regulatory regions of 18,445 <it>Mus musculus </it>genes. We discovered just 68 transcriptional programs that effectively summarised the action of 149 transcription factors on these genes. Several of these programs were significantly enriched for known biological processes and signalling pathways. One transcriptional program has a significant overlap with a reference set of cell cycle specific transcription factors.</p> <p>Conclusion</p> <p>Our method is able to pick out higher order structure from noisy sequence analyses. The transcriptional programs it identifies potentially represent common mechanisms of regulatory control across the genome. It simultaneously predicts which genes are co-regulated and which sets of transcription factors cooperate to achieve this co-regulation. The programs we discovered enable biologists to choose new genes and transcription factors to study in specific transcriptional regulatory systems.</p> |
| first_indexed | 2024-12-14T01:41:39Z |
| format | Article |
| id | doaj.art-674e230888bb436ebe8ace580c2d6c41 |
| institution | Directory Open Access Journal |
| issn | 1471-2105 |
| language | English |
| last_indexed | 2024-12-14T01:41:39Z |
| publishDate | 2009-07-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Bioinformatics |
| spelling | doaj.art-674e230888bb436ebe8ace580c2d6c412022-12-21T23:21:42ZengBMCBMC Bioinformatics1471-21052009-07-0110121810.1186/1471-2105-10-218Transcriptional programs: Modelling higher order structure in transcriptional controlWernisch LorenzOtt SaschaReid John E<p>Abstract</p> <p>Background</p> <p>Transcriptional regulation is an important part of regulatory control in eukaryotes. Even if binding motifs for transcription factors are known, the task of finding binding sites by scanning sequences is plagued by false positives. One way to improve the detection of binding sites from motifs is by taking cooperativity of transcription factor binding into account. We propose a non-parametric probabilistic model, similar to a document topic model, for detecting <it>transcriptional programs</it>, groups of cooperative transcription factors and co-regulated genes. The analysis results in transcriptional programs which generalise both transcriptional modules and TF-target gene incidence matrices and provide a higher-level summary of these structures. The method is independent of prior specification of training sets of genes, for example, via gene expression data. The analysis is based on known binding motifs.</p> <p>Results</p> <p>We applied our method to putative regulatory regions of 18,445 <it>Mus musculus </it>genes. We discovered just 68 transcriptional programs that effectively summarised the action of 149 transcription factors on these genes. Several of these programs were significantly enriched for known biological processes and signalling pathways. One transcriptional program has a significant overlap with a reference set of cell cycle specific transcription factors.</p> <p>Conclusion</p> <p>Our method is able to pick out higher order structure from noisy sequence analyses. The transcriptional programs it identifies potentially represent common mechanisms of regulatory control across the genome. It simultaneously predicts which genes are co-regulated and which sets of transcription factors cooperate to achieve this co-regulation. The programs we discovered enable biologists to choose new genes and transcription factors to study in specific transcriptional regulatory systems.</p>http://www.biomedcentral.com/1471-2105/10/218 |
| spellingShingle | Wernisch Lorenz Ott Sascha Reid John E Transcriptional programs: Modelling higher order structure in transcriptional control BMC Bioinformatics |
| title | Transcriptional programs: Modelling higher order structure in transcriptional control |
| title_full | Transcriptional programs: Modelling higher order structure in transcriptional control |
| title_fullStr | Transcriptional programs: Modelling higher order structure in transcriptional control |
| title_full_unstemmed | Transcriptional programs: Modelling higher order structure in transcriptional control |
| title_short | Transcriptional programs: Modelling higher order structure in transcriptional control |
| title_sort | transcriptional programs modelling higher order structure in transcriptional control |
| url | http://www.biomedcentral.com/1471-2105/10/218 |
| work_keys_str_mv | AT wernischlorenz transcriptionalprogramsmodellinghigherorderstructureintranscriptionalcontrol AT ottsascha transcriptionalprogramsmodellinghigherorderstructureintranscriptionalcontrol AT reidjohne transcriptionalprogramsmodellinghigherorderstructureintranscriptionalcontrol |