title: CENTDIST: discovery of co-associated factors by motif distribution.
abstract: Transcription factors (TFs) do not function alone but work together with other TFs (called co-TFs) in a combinatorial fashion to precisely control the transcription of target genes. Mining co-TFs is thus important to understand the mechanism of transcriptional regulation. Although existing methods can identify co-TFs, their accuracy depends heavily on the chosen background model and other parameters such as the enrichment window size and the PWM score cut-off. In this study, we have developed a novel web-based co-motif scanning program called CENTDIST (http://compbio.ddns.comp.nus.edu.sg/~chipseq/centdist/). In comparison to current co-motif scanning programs, CENTDIST does not require the input of any user-specific parameters and background information. Instead, CENTDIST automatically determines the best set of parameters and ranks co-TF motifs based on their distribution around ChIP-seq peaks. We tested CENTDIST on 14 ChIP-seq data sets and found CENTDIST is more accurate than existing methods. In particular, we applied CENTDIST on an Androgen Receptor (AR) ChIP-seq data set from a prostate cancer cell line and correctly predicted all known co-TFs (eight TFs) of AR in the top 20 hits as well as discovering AP4 as a novel co-TF of AR (which was missed by existing methods). Taken together, CENTDIST, which exploits the imbalanced nature of co-TF binding, is a user-friendly, parameter-less and powerful predictive web-based program for understanding the mechanism of transcriptional co-regulation.
authors: School of Computing, National University of Singapore, Computing 1, 13 Computing Drive, Singapore 117417.
authors: Zhizhuo
authors: Z
authors: Zhang
authors: Cheng Wei
authors: CW
authors: Chang
authors: Wan Ling
authors: WL
authors: Goh
authors: Wing-Kin
authors: WK
authors: Sung
authors: Edwin
authors: E
authors: Cheung
references: Endocr Rev. 2004 Apr;25(2):276-308
references: 15082523
references: DNA Res. 2009 Oct;16(5):261-73
references: 19740934
references: Nucleic Acids Res. 2007 Jul;35(Web Server issue):W245-52
references: 17576675
references: Int J Surg Pathol. 2009 Feb;17(1):16-21
references: 18480385
references: Nat Genet. 2010 Apr;42(4):343-7
references: 20208536
references: Nucleic Acids Res. 2003 Jan 1;31(1):374-8
references: 12520026
references: Nucleic Acids Res. 2008 Aug;36(14):4549-64
references: 18611952
references: Nucleic Acids Res. 2008 Jul 1;36(Web Server issue):W128-32
references: 18453628
references: Science. 2007 Jun 8;316(5830):1497-502
references: 17540862
references: PLoS One. 2008;3(12):e3932
references: 19079543
references: BMC Bioinformatics. 2008 Nov 26;9:495
references: 19036135
references: Annu Rev Physiol. 2010;72:191-218
references: 20148673
references: Bioinformatics. 2000 Jan;16(1):16-23
references: 10812473
references: Nucleic Acids Res. 2006 Jul 1;34(Web Server issue):W551-4
references: 16845068
references: Nucleic Acids Res. 2004 Jan 1;32(Database issue):D91-4
references: 14681366
references: Bioinformatics. 2010 May 1;26(9):1199-204
references: 20371496
references: Genome Biol. 2008;9(9):R137
references: 18798982
references: Radiology. 1982 Apr;143(1):29-36
references: 7063747
references: Cell. 2008 Jun 13;133(6):1106-17
references: 18555785
references: Proc Natl Acad Sci U S A. 2010 Feb 23;107(8):3639-44
references: 20139302
references: Nucleic Acids Res. 1990 Oct 25;18(20):6097-100
references: 2172928