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Technical Report
Nature Biotechnology  20, 835 - 839 (2002)
Published online: 8 July 2002; | doi:10.1038/nbt717

An algorithm for finding protein−DNA binding sites with applications to chromatin-
immunoprecipitation microarray experiments

X. Shirley Liu1, Douglas L. Brutlag2 & Jun S. Liu3

1  Stanford Medical Informatics, Stanford University, Stanford CA 94305.

2  Department of Biochemistry, Stanford University, Stanford CA 94305.

3  Department of Statistics, Harvard University, 1 Oxford Street, Cambridge MA 02138.

Correspondence should be addressed to Jun S. Liu jliu@stat.harvard.edu
Chromatin immunoprecipitation followed by cDNA microarray hybridization (ChIP−array) has become a popular procedure for studying genome-wide protein−DNA interactions and transcription regulation. However, it can only map the probable protein−DNA interaction loci within 1−2 kilobases resolution. To pinpoint interaction sites down to the base-pair level, we introduce a computational method, Motif Discovery scan (MDscan), that examines the ChIP−array-selected sequences and searches for DNA sequence motifs representing the protein−DNA interaction sites. MDscan combines the advantages of two widely adopted motif search strategies, word enumeration1, 2, 3, 4 and position-specific weight matrix updating5, 6, 7, 8, 9, and incorporates the ChIP−array ranking information to accelerate searches and enhance their success rates. MDscan correctly identified all the experimentally verified motifs from published ChIP−array experiments in yeast10, 11, 12, 13 (STE12, GAL4, RAP1, SCB, MCB, MCM1, SFF, and SWI5), and predicted two motif patterns for the differential binding of Rap1 protein in telomere regions. In our studies, the method was faster and more accurate than several established motif-finding algorithms5, 8, 9. MDscan can be used to find DNA motifs not only in ChIP−array experiments but also in other experiments in which a subgroup of the sequences can be inferred to contain relatively abundant motif sites. The MDscan web server can be accessed at http://BioProspector.stanford.edu/MDscan/.

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Nature Biotechnology
ISSN: 1087-0156
EISSN: 1546-1696
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