Cargando…
Assessing quality and completeness of human transcriptional regulatory pathways on a genome-wide scale
BACKGROUND: Pathway databases are becoming increasingly important and almost omnipresent in most types of biological and translational research. However, little is known about the quality and completeness of pathways stored in these databases. The present study conducts a comprehensive assessment of...
Autores principales: | , , , |
---|---|
Formato: | Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2011
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3055855/ https://www.ncbi.nlm.nih.gov/pubmed/21356087 http://dx.doi.org/10.1186/1745-6150-6-15 |
_version_ | 1782200151436165120 |
---|---|
author | Shmelkov, Evgeny Tang, Zuojian Aifantis, Iannis Statnikov, Alexander |
author_facet | Shmelkov, Evgeny Tang, Zuojian Aifantis, Iannis Statnikov, Alexander |
author_sort | Shmelkov, Evgeny |
collection | PubMed |
description | BACKGROUND: Pathway databases are becoming increasingly important and almost omnipresent in most types of biological and translational research. However, little is known about the quality and completeness of pathways stored in these databases. The present study conducts a comprehensive assessment of transcriptional regulatory pathways in humans for seven well-studied transcription factors: MYC, NOTCH1, BCL6, TP53, AR, STAT1, and RELA. The employed benchmarking methodology first involves integrating genome-wide binding with functional gene expression data to derive direct targets of transcription factors. Then the lists of experimentally obtained direct targets are compared with relevant lists of transcriptional targets from 10 commonly used pathway databases. RESULTS: The results of this study show that for the majority of pathway databases, the overlap between experimentally obtained target genes and targets reported in transcriptional regulatory pathway databases is surprisingly small and often is not statistically significant. The only exception is MetaCore pathway database which yields statistically significant intersection with experimental results in 84% cases. Additionally, we suggest that the lists of experimentally derived direct targets obtained in this study can be used to reveal new biological insight in transcriptional regulation and suggest novel putative therapeutic targets in cancer. CONCLUSIONS: Our study opens a debate on validity of using many popular pathway databases to obtain transcriptional regulatory targets. We conclude that the choice of pathway databases should be informed by solid scientific evidence and rigorous empirical evaluation. REVIEWERS: This article was reviewed by Prof. Wing Hung Wong, Dr. Thiago Motta Venancio (nominated by Dr. L Aravind), and Prof. Geoff J McLachlan. |
format | Text |
id | pubmed-3055855 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-30558552011-03-12 Assessing quality and completeness of human transcriptional regulatory pathways on a genome-wide scale Shmelkov, Evgeny Tang, Zuojian Aifantis, Iannis Statnikov, Alexander Biol Direct Research BACKGROUND: Pathway databases are becoming increasingly important and almost omnipresent in most types of biological and translational research. However, little is known about the quality and completeness of pathways stored in these databases. The present study conducts a comprehensive assessment of transcriptional regulatory pathways in humans for seven well-studied transcription factors: MYC, NOTCH1, BCL6, TP53, AR, STAT1, and RELA. The employed benchmarking methodology first involves integrating genome-wide binding with functional gene expression data to derive direct targets of transcription factors. Then the lists of experimentally obtained direct targets are compared with relevant lists of transcriptional targets from 10 commonly used pathway databases. RESULTS: The results of this study show that for the majority of pathway databases, the overlap between experimentally obtained target genes and targets reported in transcriptional regulatory pathway databases is surprisingly small and often is not statistically significant. The only exception is MetaCore pathway database which yields statistically significant intersection with experimental results in 84% cases. Additionally, we suggest that the lists of experimentally derived direct targets obtained in this study can be used to reveal new biological insight in transcriptional regulation and suggest novel putative therapeutic targets in cancer. CONCLUSIONS: Our study opens a debate on validity of using many popular pathway databases to obtain transcriptional regulatory targets. We conclude that the choice of pathway databases should be informed by solid scientific evidence and rigorous empirical evaluation. REVIEWERS: This article was reviewed by Prof. Wing Hung Wong, Dr. Thiago Motta Venancio (nominated by Dr. L Aravind), and Prof. Geoff J McLachlan. BioMed Central 2011-02-28 /pmc/articles/PMC3055855/ /pubmed/21356087 http://dx.doi.org/10.1186/1745-6150-6-15 Text en Copyright ©2011 Shmelkov et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Shmelkov, Evgeny Tang, Zuojian Aifantis, Iannis Statnikov, Alexander Assessing quality and completeness of human transcriptional regulatory pathways on a genome-wide scale |
title | Assessing quality and completeness of human transcriptional regulatory pathways on a genome-wide scale |
title_full | Assessing quality and completeness of human transcriptional regulatory pathways on a genome-wide scale |
title_fullStr | Assessing quality and completeness of human transcriptional regulatory pathways on a genome-wide scale |
title_full_unstemmed | Assessing quality and completeness of human transcriptional regulatory pathways on a genome-wide scale |
title_short | Assessing quality and completeness of human transcriptional regulatory pathways on a genome-wide scale |
title_sort | assessing quality and completeness of human transcriptional regulatory pathways on a genome-wide scale |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3055855/ https://www.ncbi.nlm.nih.gov/pubmed/21356087 http://dx.doi.org/10.1186/1745-6150-6-15 |
work_keys_str_mv | AT shmelkovevgeny assessingqualityandcompletenessofhumantranscriptionalregulatorypathwaysonagenomewidescale AT tangzuojian assessingqualityandcompletenessofhumantranscriptionalregulatorypathwaysonagenomewidescale AT aifantisiannis assessingqualityandcompletenessofhumantranscriptionalregulatorypathwaysonagenomewidescale AT statnikovalexander assessingqualityandcompletenessofhumantranscriptionalregulatorypathwaysonagenomewidescale |