dorsal/arxiv
View SchemaAb initio identification of putative human transcription factor binding sites by comparative genomics
| Authors | Davide Cora', Carl Herrmann, Christoph Dieterich, Ferdinando Di Cunto, Paolo Provero, Michele Caselle |
|---|---|
| Categories | |
| ArXiv ID | q-bio/0505005 |
| URL | https://arxiv.org/abs/q-bio/0505005 |
| Journal | BMC Bioinformatics 2005, 6:110 |
Abstract
We discuss a simple and powerful approach for the ab initio identification of cis-regulatory motifs involved in transcriptional regulation. The method we present integrates several elements: human-mouse comparison, statistical analysis of genomic sequences and the concept of coregulation. We apply it to a complete scan of the human genome. By using the catalogue of conserved upstream sequences collected in the CORG database we construct sets of genes sharing the same overrepresented motif (short DNA sequence) in their upstream regions both in human and in mouse. We perform this construction for all possible motifs from 5 to 8 nucleotides in length and then filter the resulting sets looking for two types of evidence of coregulation: first, we analyze the Gene Ontology annotation of the genes in the set, searching for statistically significant common annotations; second, we analyze the expression profiles of the genes in the set as measured by microarray experiments, searching for evidence of coexpression. The sets which pass one or both filters are conjectured to contain a significant fraction of coregulated genes, and the upstream motifs characterizing the sets are thus good candidates to be the binding sites of the TF's involved in such regulation. In this way we find various known motifs and also some new candidate binding sites.
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"abstract": "We discuss a simple and powerful approach for the ab initio identification of\ncis-regulatory motifs involved in transcriptional regulation. The method we\npresent integrates several elements: human-mouse comparison, statistical\nanalysis of genomic sequences and the concept of coregulation. We apply it to a\ncomplete scan of the human genome. By using the catalogue of conserved upstream\nsequences collected in the CORG database we construct sets of genes sharing the\nsame overrepresented motif (short DNA sequence) in their upstream regions both\nin human and in mouse. We perform this construction for all possible motifs\nfrom 5 to 8 nucleotides in length and then filter the resulting sets looking\nfor two types of evidence of coregulation: first, we analyze the Gene Ontology\nannotation of the genes in the set, searching for statistically significant\ncommon annotations; second, we analyze the expression profiles of the genes in\nthe set as measured by microarray experiments, searching for evidence of\ncoexpression. The sets which pass one or both filters are conjectured to\ncontain a significant fraction of coregulated genes, and the upstream motifs\ncharacterizing the sets are thus good candidates to be the binding sites of the\nTF\u0027s involved in such regulation. In this way we find various known motifs and\nalso some new candidate binding sites.",
"arxiv_id": "q-bio/0505005",
"authors": [
"Davide Cora\u0027",
"Carl Herrmann",
"Christoph Dieterich",
"Ferdinando Di Cunto",
"Paolo Provero",
"Michele Caselle"
],
"categories": [
"q-bio.GN"
],
"journal_ref": "BMC Bioinformatics 2005, 6:110",
"title": "Ab initio identification of putative human transcription factor binding sites by comparative genomics",
"url": "https://arxiv.org/abs/q-bio/0505005"
},
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