SigSeeker: An Ensemble for Analysis of ChIPSeq, MethylSeq and HistoneSeq data

Wednesday, September 24, 2014 — Poster Session IV
10:00 a.m. –12:00 p.m.	FAES Academic Center	NHGRI	COMPBIO-9

* FARE Award Winner

Authors

• J Lichtenberg
• E.F. Heuston
• D.M. Bodine

Abstract

Next-Generation Sequencing (NGS) enables the genome-wide analysis of methylation, transcription factor occupancy and histone modifications. Analysis tools for NGS data use different algorithms, leading to different results from the same data. Findings corroborated by multiple programs represent the highest confidence data and should be standard in genomics. No integrated framework exists that allows analysis by multiple approaches, reducing the utility of NGS data to the field of genomics. We developed SigSeeker, a computational ensemble that can be used to process existing and novel NGS data. SigSeeker maps sequencing reads, detects enriched regions, and correlates them regions with expression data. Studying genome-wide patterns of methylation and expression in primary mouse hematopoietic stem and progenitor cells, showed a consistent decline in methylation from hematopoietic stem cells to committed erythroblasts and megakaryocytes. Promoters of expressed genes were hypomethylated in all cell types. Methylation and GATA1 binding in the gene body lead to silencing in erythroblasts while NFE2 binding lead to activation in megakaryocytes. SigSeeker demonstrates that epigenetic modifications change dramatically during hematopoiesis and identifies critical regions of the genome that regulate hematopoietic cell fate. Our ensemble technique exceeds the sensitivity of single approaches and is ideal for identifying high confidence epigenetic profiles.

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