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PePr: a peak-calling prioritization pipeline to identify consistent or differential peaks from replicated ChIP-Seq
Yanxiao Zhang1, Yu-Hsuan Lin1, Timothy D Johnson1
1Department of Computational Medicine and Bioinformatics, Department of Biostatistics and Department of Environmental Health Sciences, School of Public Health, University of Michigan, Ann Arbor, MI 48109, USA.
A new pipeline, PePr, analyzes ChIP-Seq data with biological replicates to find consistent or differential transcription factor binding sites. It outperforms existing methods in identifying reliable binding regions and analyzing histone modification data.
Area of Science:
- Genomics
- Epigenetics
- Bioinformatics
Background:
- ChIP-Seq is standard for identifying genome-wide DNA-binding sites for transcription factors (TFs) and histone modifications.
- Analyzing experiments with biological replicates is crucial, especially in epigenomics due to sample variability.
- Current tools lack robust group comparison capabilities for ChIP-Seq data.
Purpose of the Study:
- To develop a computational pipeline for analyzing ChIP-Seq experiments with biological replicates.
- To enable the identification of consistent and differential binding sites across groups of samples.
- To provide a tool that addresses the limitations of existing methods for comparative ChIP-Seq analysis.
Main Methods:
- Developed PePr (peak-calling prioritization pipeline) using a negative binomial distribution model for read counts.
- Implemented a local variance estimation method to rank binding sites based on variability.
- Compared PePr against existing approaches using eight TF datasets and histone modification data.
Main Results:
- PePr successfully identifies consistent TF binding sites with high read counts and motif occurrence.
- The pipeline outperforms other methods in identifying differential binding regions for histone modifications.
- PePr demonstrates superior performance in False Discovery Rate (FDR) analysis for differential binding.
Conclusions:
- PePr is an effective tool for analyzing ChIP-Seq data with biological replicates.
- The pipeline enhances the identification of reliable TF binding sites and differential histone modification regions.
- PePr offers improved accuracy and scalability for comparative epigenomic analyses.
