PICS: Probabilistic Inference for ChIP-seq
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Abstract: ChIP-seq, which combines chromatin immunoprecipitation with massively parallel short-read sequencing, can profile in vivo genome-wide transcription factor-DNA association with higher sensitivity, specificity and spatial resolution than ChIP-chip. While it presents new opportunities for research, ChIP-seq poses new challenges for statistical analysis that derive from the complexity of the biological systems characterized and the variability and biases in its digital sequence data. We propose a method called PICS (Probabilistic Inference for ChIP-seq) for extracting information from ChIP-seq aligned-read data in order to identify regions bound by transcription factors. PICS identifies enriched regions by modeling local concentrations of directional reads, and uses DNA fragment length prior information to discriminate closely adjacent binding events via a Bayesian hierarchical t-mixture model. Its per-event fragment length estimates also allow it to remove from analysis regions that have atypical lengths. PICS uses pre-calculated, whole-genome read mappability profiles and a truncated t-distribution to adjust binding event models for reads that are missing due to local genome repetitiveness. It estimates uncertainties in model parameters that can be used to define confidence regions on binding event locations and to filter estimates. Finally, PICS calculates a per-event enrichment score relative to a control sample, and can use a control sample to estimate a false discovery rate. We compared PICS to the alternative methods MACS, QuEST, and CisGenome, using published GABP and FOXA1 data sets from human cell lines, and found that PICS' predicted binding sites were more consistent with computationally predicted binding motifs.
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Cites work
- scientific article; zbMATH DE number 3567782 (Why is no real title available?)
- scientific article; zbMATH DE number 1059776 (Why is no real title available?)
- A Flexible and Powerful Bayesian Hierarchical Model for ChIP-Chip Experiments
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Cited in
(5)- Bayesian hidden Markov models to identify RNA-protein interaction sites in PAR-CLIP
- A statistical framework for the analysis of ChIP-seq data
- Using informative multinomial-Dirichlet prior in a t-mixture with reversible jump estimation of nucleosome positions for genome-wide profiling
- PICS
- Multiple testing of local maxima for detection of peaks in ChIP-Seq data
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