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    BMC Bioinformatics. 2009 Sep 22;10:305.

    Strategies for analyzing highly enriched IP-chip datasets.

    Knott SR, Viggiani CJ, Aparicio OM, Tavaré S.

    Molecular and Computational Biology Program, University of Southern California, Ray Irani Hall, University Park Campus, Los Angeles, CA 90089-2910, USA. knott@usc.edu

    BACKGROUND: Chromatin immunoprecipitation on tiling arrays (ChIP-chip) has been employed to examine features such as protein binding and histone modifications on a genome-wide scale in a variety of cell types. Array data from the latter studies typically have a high proportion of enriched probes whose signals vary considerably (due to heterogeneity in the cell population), and this makes their normalization and downstream analysis difficult. RESULTS: Here we present strategies for analyzing such experiments, focusing our discussion on the analysis of Bromodeoxyruridine (BrdU) immunoprecipitation on tiling array (BrdU-IP-chip) datasets. BrdU-IP-chip experiments map large, recently replicated genomic regions and have similar characteristics to histone modification/location data. To prepare such data for downstream analysis we employ a dynamic programming algorithm that identifies a set of putative unenriched probes, which we use for both within-array and between-array normalization. We also introduce a second dynamic programming algorithm that incorporates a priori knowledge to identify and quantify positive signals in these datasets. CONCLUSION: Highly enriched IP-chip datasets are often difficult to analyze with traditional array normalization and analysis strategies. Here we present and test a set of analytical tools for their normalization and quantification that allows for accurate identification and analysis of enriched regions.

    PMID: 19772646 [PubMed - in process]

    PMCID: PMC2759964

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