Clipick

A sensitive peak caller for expression-based deconvolution of HITS-CLIP signals

Sihyung Park, Seung Hyun Ahn, Eun Sol Cho, You Kyung Cho, Eun Sook Jang, Sung Wook Chi

Research output: Contribution to journalArticle

Abstract

High-throughput sequencing of RNAs isolated by crosslinking immunoprecipitation (HITS-CLIP, also called CLIP-Seq) has been used to map global RNA–protein interactions. However, a critical caveat of HITS-CLIP results is that they contain nonlinear background noise––different extent of nonspecific interactions caused by individual transcript abundance––that has been inconsiderately normalized, resulting in sacrifice of sensitivity. To properly deconvolute RNA–protein interactions, we have implemented CLIPick, a flexible peak calling pipeline for analyzing HITS-CLIP data, which statistically determines the signal-to-noise ratio for each transcript based on the expression-dependent background simulation. Comprising of streamlined Python modules with an easy-to-use standalone graphical user interface, CLIPick robustly identifies significant peaks and quantitatively defines footprint regions within which RNA–protein interactions were occurred. CLIPick outperforms other peak callers in accuracy and sensitivity, selecting the largest number of peaks particularly in lowly expressed transcripts where such marginal signals are hard to discriminate. Specifically, the application of CLIPick to Argonaute (Ago) HITS-CLIP data were sensitive enough to uncover extended features of microRNA target sites, and these sites were experimentally validated. CLIPick enables to resolve critical interactions in a wide spectrum of transcript levels and extends the scope of HITS-CLIP analysis.

Original languageEnglish
Pages (from-to)11153-11168
Number of pages16
JournalNucleic acids research
Volume46
Issue number21
DOIs
Publication statusPublished - 2018 Jan 1

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Boidae
High-Throughput Nucleotide Sequencing
Signal-To-Noise Ratio
MicroRNAs
Immunoprecipitation

ASJC Scopus subject areas

  • Genetics

Cite this

Clipick : A sensitive peak caller for expression-based deconvolution of HITS-CLIP signals. / Park, Sihyung; Ahn, Seung Hyun; Cho, Eun Sol; Cho, You Kyung; Jang, Eun Sook; Chi, Sung Wook.

In: Nucleic acids research, Vol. 46, No. 21, 01.01.2018, p. 11153-11168.

Research output: Contribution to journalArticle

Park, Sihyung ; Ahn, Seung Hyun ; Cho, Eun Sol ; Cho, You Kyung ; Jang, Eun Sook ; Chi, Sung Wook. / Clipick : A sensitive peak caller for expression-based deconvolution of HITS-CLIP signals. In: Nucleic acids research. 2018 ; Vol. 46, No. 21. pp. 11153-11168.
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