Regulation of gene expression by a transcription factor requires physical interaction between the factor and the DNA, which can be described by a statistical mechanical model. Based on this model, the MatrixREDUCE algorithm uses genome-wide occupancy data for a transcription factor (e.g. ChIP-chip or mRNA expression data) and associated nucleotide sequences to discover the sequence-specific binding affinity of the transcription factor. The sequence specificity of the transcription factor\'s DNA-binding domain is modeled using a position-specific affinity matrix (PSAM), representing the change in the binding affinity (Kd) whenever a specific position within a reference binding sequence is mutated. The PSAM can be transformed into affinity logo for visualization using the utility program AffinityLogo, and a MatrixREDUCE run can be summarized in an easy-to-navigate webpage using HTMLSummary.
The input to MatrixREDUCE is a sequence file in FASTA format and an expression data file in tab-delimited text format (missing values are allowed). Output data include PSAMs in numeric and graphical format, parameters of the fitted model, and an HTML summary page.
The MatrixREDUCE software package has been developed in the laboratory of Dr. Harmen Bussemaker at the Department of Biological Sciences, Columbia University in the City of New York. The package was started by Barrett Foat for his Ph.D. project, and consisted of several C programs (calling GSL functions) glued together with Perl scripts. Based on Barrett\'s original work, Xiang-Jun Lu has rewritten and improved the source code using pure ANSI C, calling Numerical Recipes (NR) routines to make the program more efficient and self-contained. Later on, two related C programs, AffinityLogo and HTMLSummary, and other scripts were added to form the current package.
This work was supported by National Institutes of Health Grant HG003008 (to Harmen Bussemaker). MatrixREDUCE was initially reported in the paper: "Profiling condition-specific, genome-wide regulation of mRNA stability in yeast" by Barrett Foat et al. [PNAS 102(49), 17675-17680, December 6, 2005], and most recently in: "Statistical mechanical modeling of genome-wide transcription factor occupancy data by MatrixREDUCE" by Barrett Foat et al. [Bioinformatics, 2006 22(14):e141-e149].
This downloadable version of MatrixREDUCE contains the source code version. If you would like already compiled versions of the program please contact us at Columbia Technology Ventures at
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