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ChEA: transcription factor regulation inferred from integrating genome-wide ChIP-X experiments.

MOTIVATION: Experiments such as ChIP-chip, ChIP-seq, ChIP-PET and DamID (the four methods referred herein as ChIP-X) are used to profile the binding of transcription factors to DNA at a genome-wide scale. Such experiments provide hundreds to thousands of potential binding sites for a given transcription factor in proximity to gene coding regions. RESULTS: In order to integrate data from such studies and utilize it for further biological discovery, we collected interactions from such experiments to construct a mammalian ChIP-X database. The database contains 189,933 interactions, manually extracted from 87 publications, describing the binding of 92 transcription factors to 31,932 target genes. We used the database to analyze mRNA expression data where we perform gene-list enrichment analysis using the ChIP-X database as the prior biological knowledge gene-list library. The system is delivered as a web-based interactive application called ChIP Enrichment Analysis (ChEA). With ChEA, users can input lists of mammalian gene symbols for which the program computes over-representation of transcription factor targets from the ChIP-X database. The ChEA database allowed us to reconstruct an initial network of transcription factors connected based on shared overlapping targets and binding site proximity. To demonstrate the utility of ChEA we present three case studies. We show how by combining the Connectivity Map (CMAP) with ChEA, we can rank pairs of compounds to be used to target specific transcription factor activity in cancer cells. AVAILABILITY: The ChEA software and ChIP-X database is freely available online at: http://amp.pharm.mssm.edu/lib/chea.jsp.

Pubmed ID: 20709693

Authors

  • Lachmann A
  • Xu H
  • Krishnan J
  • Berger SI
  • Mazloom AR
  • Ma'ayan A

Journal

Bioinformatics (Oxford, England)

Publication Data

October 1, 2010

Associated Grants

  • Agency: NCRR NIH HHS, Id: KL2 RR029885
  • Agency: NCRR NIH HHS, Id: KL2 RR029885-01
  • Agency: NCRR NIH HHS, Id: KL2RR029885-0109
  • Agency: NIGMS NIH HHS, Id: P50 GM071558
  • Agency: NIGMS NIH HHS, Id: P50 GM071558-01A2
  • Agency: NIGMS NIH HHS, Id: P50GM071558-01A27398
  • Agency: NIDDK NIH HHS, Id: R01 DK088541
  • Agency: NIDDK NIH HHS, Id: R01 DK088541-01A1
  • Agency: NIDDK NIH HHS, Id: R01 DK088541-02
  • Agency: NIGMS NIH HHS, Id: R01 GM054508
  • Agency: NIDA NIH HHS, Id: R01DA15446
  • Agency: NIDDK NIH HHS, Id: R01DK088541
  • Agency: NIGMS NIH HHS, Id: R01GM054508
  • Agency: NLM NIH HHS, Id: RC2 LM010994
  • Agency: NLM NIH HHS, Id: RC2 LM010994-01

Mesh Terms

  • Chromatin Immunoprecipitation
  • Databases, Genetic
  • Gene Expression Regulation
  • Genome
  • Software
  • Transcription Factors