Cargando…

Identification of conserved regulatory elements by comparative genome analysis

BACKGROUND: For genes that have been successfully delineated within the human genome sequence, most regulatory sequences remain to be elucidated. The annotation and interpretation process requires additional data resources and significant improvements in computational methods for the detection of re...

Descripción completa

Detalles Bibliográficos
Autores principales: Lenhard, Boris, Sandelin, Albin, Mendoza, Luis, Engström, Pär, Jareborg, Niclas, Wasserman, Wyeth W
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2003
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC193685/
https://www.ncbi.nlm.nih.gov/pubmed/12760745
http://dx.doi.org/10.1186/1475-4924-2-13
_version_ 1782120911010267136
author Lenhard, Boris
Sandelin, Albin
Mendoza, Luis
Engström, Pär
Jareborg, Niclas
Wasserman, Wyeth W
author_facet Lenhard, Boris
Sandelin, Albin
Mendoza, Luis
Engström, Pär
Jareborg, Niclas
Wasserman, Wyeth W
author_sort Lenhard, Boris
collection PubMed
description BACKGROUND: For genes that have been successfully delineated within the human genome sequence, most regulatory sequences remain to be elucidated. The annotation and interpretation process requires additional data resources and significant improvements in computational methods for the detection of regulatory regions. One approach of growing popularity is based on the preferential conservation of functional sequences over the course of evolution by selective pressure, termed 'phylogenetic footprinting'. Mutations are more likely to be disruptive if they appear in functional sites, resulting in a measurable difference in evolution rates between functional and non-functional genomic segments. RESULTS: We have devised a flexible suite of methods for the identification and visualization of conserved transcription-factor-binding sites. The system reports those putative transcription-factor-binding sites that are both situated in conserved regions and located as pairs of sites in equivalent positions in alignments between two orthologous sequences. An underlying collection of metazoan transcription-factor-binding profiles was assembled to facilitate the study. This approach results in a significant improvement in the detection of transcription-factor-binding sites because of an increased signal-to-noise ratio, as demonstrated with two sets of promoter sequences. The method is implemented as a graphical web application, ConSite, which is at the disposal of the scientific community at . CONCLUSIONS: Phylogenetic footprinting dramatically improves the predictive selectivity of bioinformatic approaches to the analysis of promoter sequences. ConSite delivers unparalleled performance using a novel database of high-quality binding models for metazoan transcription factors. With a dynamic interface, this bioinformatics tool provides broad access to promoter analysis with phylogenetic footprinting.
format Text
id pubmed-193685
institution National Center for Biotechnology Information
language English
publishDate 2003
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-1936852003-09-15 Identification of conserved regulatory elements by comparative genome analysis Lenhard, Boris Sandelin, Albin Mendoza, Luis Engström, Pär Jareborg, Niclas Wasserman, Wyeth W J Biol Research Article BACKGROUND: For genes that have been successfully delineated within the human genome sequence, most regulatory sequences remain to be elucidated. The annotation and interpretation process requires additional data resources and significant improvements in computational methods for the detection of regulatory regions. One approach of growing popularity is based on the preferential conservation of functional sequences over the course of evolution by selective pressure, termed 'phylogenetic footprinting'. Mutations are more likely to be disruptive if they appear in functional sites, resulting in a measurable difference in evolution rates between functional and non-functional genomic segments. RESULTS: We have devised a flexible suite of methods for the identification and visualization of conserved transcription-factor-binding sites. The system reports those putative transcription-factor-binding sites that are both situated in conserved regions and located as pairs of sites in equivalent positions in alignments between two orthologous sequences. An underlying collection of metazoan transcription-factor-binding profiles was assembled to facilitate the study. This approach results in a significant improvement in the detection of transcription-factor-binding sites because of an increased signal-to-noise ratio, as demonstrated with two sets of promoter sequences. The method is implemented as a graphical web application, ConSite, which is at the disposal of the scientific community at . CONCLUSIONS: Phylogenetic footprinting dramatically improves the predictive selectivity of bioinformatic approaches to the analysis of promoter sequences. ConSite delivers unparalleled performance using a novel database of high-quality binding models for metazoan transcription factors. With a dynamic interface, this bioinformatics tool provides broad access to promoter analysis with phylogenetic footprinting. BioMed Central 2003 2003-05-22 /pmc/articles/PMC193685/ /pubmed/12760745 http://dx.doi.org/10.1186/1475-4924-2-13 Text en Copyright © 2003 Lenhard et al., licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.
spellingShingle Research Article
Lenhard, Boris
Sandelin, Albin
Mendoza, Luis
Engström, Pär
Jareborg, Niclas
Wasserman, Wyeth W
Identification of conserved regulatory elements by comparative genome analysis
title Identification of conserved regulatory elements by comparative genome analysis
title_full Identification of conserved regulatory elements by comparative genome analysis
title_fullStr Identification of conserved regulatory elements by comparative genome analysis
title_full_unstemmed Identification of conserved regulatory elements by comparative genome analysis
title_short Identification of conserved regulatory elements by comparative genome analysis
title_sort identification of conserved regulatory elements by comparative genome analysis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC193685/
https://www.ncbi.nlm.nih.gov/pubmed/12760745
http://dx.doi.org/10.1186/1475-4924-2-13
work_keys_str_mv AT lenhardboris identificationofconservedregulatoryelementsbycomparativegenomeanalysis
AT sandelinalbin identificationofconservedregulatoryelementsbycomparativegenomeanalysis
AT mendozaluis identificationofconservedregulatoryelementsbycomparativegenomeanalysis
AT engstrompar identificationofconservedregulatoryelementsbycomparativegenomeanalysis
AT jareborgniclas identificationofconservedregulatoryelementsbycomparativegenomeanalysis
AT wassermanwyethw identificationofconservedregulatoryelementsbycomparativegenomeanalysis