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

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 rend...

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Detalles Bibliográficos
Autores principales: Meers, Michael P., Tenenbaum, Dan, Henikoff, Steven
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6624997/
https://www.ncbi.nlm.nih.gov/pubmed/31300027
http://dx.doi.org/10.1186/s13072-019-0287-4
Descripción
Sumario: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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13072-019-0287-4) contains supplementary material, which is available to authorized users.