Peak calling by Sparse Enrichment Analysis for CUT&RUN chromatin profiling

Michael P. Meers, Dan Tenenbaum, Steven Henikoff

Research output: Contribution to journalArticlepeer-review

86 Scopus citations

Abstract

Background: CUT&RUN is an efficient epigenome profiling method that identifies sites of DNA binding protein enrichment genome-wide with high signal to noise and low sequencing requirements. Currently, the analysis of CUT&RUN data is complicated by its exceptionally low background, which renders programs designed for analysis of ChIP-seq data vulnerable to oversensitivity in identifying sites of protein binding. Results: Here we introduce Sparse Enrichment Analysis for CUT&RUN (SEACR), an analysis strategy that uses the global distribution of background signal to calibrate a simple threshold for peak calling. SEACR discriminates between true and false-positive peaks with near-perfect specificity from "gold standard" CUT&RUN datasets and efficiently identifies enriched regions for several different protein targets. We also introduce a web server (http://seacr.fredhutch.org) for plug-and-play analysis with SEACR that facilitates maximum accessibility across users of all skill levels. Conclusions: SEACR is a highly selective peak caller that definitively validates the accuracy of CUT&RUN for datasets with known true negatives. Its ease of use and performance in comparison with existing peak calling strategies make it an ideal choice for analyzing CUT&RUN data.

Original languageEnglish
Article number42
JournalEpigenetics and Chromatin
Volume12
Issue number1
DOIs
StatePublished - Jul 12 2019

Keywords

  • CUT&RUN
  • Epigenome profiling
  • Peak calling

Fingerprint

Dive into the research topics of 'Peak calling by Sparse Enrichment Analysis for CUT&RUN chromatin profiling'. Together they form a unique fingerprint.

Cite this