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Related Experiment Videos

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

X Shirley Liu1, Douglas L Brutlag, Jun S Liu

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

Nature Biotechnology
|July 9, 2002
PubMed
Summary

A new computational method, Motif Discovery scan (MDscan), precisely identifies protein-DNA interaction sites from ChIP-array data. This tool enhances the resolution of genome-wide studies, improving accuracy and speed in motif discovery.

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Area of Science:

  • Genomics
  • Computational Biology
  • Molecular Biology

Background:

  • Chromatin immunoprecipitation followed by cDNA microarray hybridization (ChIP-array) is widely used for genome-wide protein-DNA interaction studies.
  • ChIP-array typically offers a resolution of 1-2 kilobases, limiting precise localization of interaction sites.

Purpose of the Study:

  • To develop a computational method for pinpointing protein-DNA interaction sites at base-pair resolution.
  • To enhance the accuracy and efficiency of motif discovery in ChIP-array experiments.

Main Methods:

  • Introduction of Motif Discovery scan (MDscan), a computational method for analyzing ChIP-array sequences.
  • MDscan integrates word enumeration and position-specific weight matrix updating, utilizing ChIP-array ranking information.

Related Experiment Videos

  • Validation using published yeast ChIP-array experiments.

    • Main Results:

    • MDscan successfully identified all experimentally verified motifs (STE12, GAL4, RAP1, SCB, MCB, MCM1, SFF, SWI5) in yeast.
    • The method predicted novel motif patterns for Rap1 protein binding in telomere regions.
    • MDscan demonstrated superior speed and accuracy compared to established motif-finding algorithms.

    Conclusions:

    • MDscan provides base-pair resolution for identifying protein-DNA interactions, significantly improving upon ChIP-array limitations.
    • The method is applicable to various experimental contexts where motif abundance can be inferred.
    • A web server for MDscan is available at http://BioProspector.stanford.edu/MDscan/.