CASPR, an analysis pipeline for single and paired guide RNA CRISPR screens, reveals optimal target selection for long non-coding RNAs

Judith Bergadà-Pijuan; Carlos Pulido-Quetglas; Adrienne Vancura; Rory Johnson

doi:10.1093/bioinformatics/btz811

CASPR, an analysis pipeline for single and paired guide RNA CRISPR screens, reveals optimal target selection for long non-coding RNAs

Bioinformatics. 2020 Mar 1;36(6):1673-1680. doi: 10.1093/bioinformatics/btz811.

Authors

Judith Bergadà-Pijuan^{1

2}, Carlos Pulido-Quetglas^{1

2

3}, Adrienne Vancura^{1

2}, Rory Johnson^{1

2}

Affiliations

¹ Department of Medical Oncology, Inselspital, Bern University Hospital.
² Department for BioMedical Research, University of Bern, Bern 3012, Switzerland.
³ Graduate School of Cellular and Biomedical Sciences, University of Bern, Bern 3012, Switzerland.

PMID: 31681950
DOI: 10.1093/bioinformatics/btz811

Abstract

Motivation: CRISPR-Cas9 loss-of-function (LOF) pooled screening promises to identify which long non-coding RNAs (lncRNAs), amongst the many thousands to have been annotated so far, are capable of mediating cellular functions. The two principal LOF perturbations, CRISPR-inhibition and CRISPR-deletion, employ one and two guide RNAs, respectively. However, no software solution has the versatility to identify hits across both modalities, and the optimal design parameters for such screens remain poorly understood.

Results: Here, we present CRISPR Analysis for Single and Paired RNA-guides (CASPR), a user-friendly, end-to-end screen analysis tool. CASPR is compatible with both CRISPRi and CRISPR-del screens, and balances sensitivity and specificity by generating consensus predictions from multiple algorithms. Benchmarking on ground-truth sets of cancer-associated lncRNAs demonstrates CASPR's improved sensitivity with respect to existing methods. Applying CASPR to published screens, we identify two parameters that predict lncRNA hits: expression and annotation quality of the transcription start site. Thus, CASPR is a versatile and complete solution for lncRNA CRISPR screen analysis, and reveals principles for including lncRNAs in screening libraries.

Availability and implementation: https://judithbergada.github.io/CASPR/.

Supplementary information: Supplementary data are available at Bioinformatics online.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

CRISPR-Cas Systems
Clustered Regularly Interspaced Short Palindromic Repeats
RNA, Guide, CRISPR-Cas Systems*
RNA, Long Noncoding*
Software

Substances

RNA, Guide, CRISPR-Cas Systems
RNA, Long Noncoding