Title
W-AlignACE: an improved Gibbs sampling algorithm based on more accurate position weight matrices learned from sequence and gene expression/ChIP-chip data.
Abstract
Motivation: Position weight matrices (PWMs) are widely used to depict the DNA binding preferences of transcription factors (TFs) in computational molecular biology and regulatory genomics. Thus, learning an accurate PWM to characterize the binding sites of a specific TF is a fundamental problem that plays an important role in modeling regulatory motifs and also in discovering the regulatory targets of TFs. Results: We study the question of how to learn a more accurate PWM from both binding sequences and gene expression (or ChIP-chip) data, and propose to find a PWM such that the likelihood of simultaneously observing both binding sequences and their associated gene expression (or ChIP-chip) data is maximised. To solve the above maximum likelihood problem, a sequence weighting scheme is thus introduced based on the observation that binding sites inducing drastic fold changes in mRNA expression (or showing strong binding ratios in ChIP experiments) are likely to represent a true motif. We have incorporated this new learning approach into the popular motif finding program AlignACE. The modified program, called W-AlignACE, is compared with three other programs (AlignACE, MDscan and MotifRegressor) on a variety of datasets, including simulated data, mRNA expression and ChIP-chip data. These tests demonstrate that W-AlignACE is an effective tool for discovering TF binding motifs from gene expression (or ChIP-chip) data and, in particular, has the ability to find very weak motifs like DIG1 and GAL4. Availability: http://www.ntu.edu.sg/home/ChenXin/Gibbs Contact: chenxin@ntu.edu.sg Supplementary information: Supplementary data are available at Bioinformatics online.
Year
DOI
Venue
2008
10.1093/bioinformatics/btn088
BIOINFORMATICS
Keywords
Field
DocType
contact: chenxin@ntu.edu.sg supplementary materials: available at bioinformatics online,transcription factor,gibbs sampling,chip,gene expression,maximum likelihood,binding site
Weighting,Gene,Binding site,Nucleic acid sequence,Computer science,Genomics,Bioinformatics,DNA microarray,Gibbs sampling,Transcription factor
Journal
Volume
Issue
ISSN
24
9
1367-4803
Citations 
PageRank 
References 
4
0.43
10
Authors
4
Name
Order
Citations
PageRank
Xin Chen11539.25
Lingqiong Guo240.43
Zhaocheng Fan340.43
Tao Jiang41809155.32