PMID- 28724352 OWN - NLM STAT- MEDLINE DCOM- 20180313 LR - 20240104 IS - 1471-2164 (Electronic) IS - 1471-2164 (Linking) VI - 18 IP - 1 DP - 2017 Jul 19 TI - A permutation-based non-parametric analysis of CRISPR screen data. PG - 545 LID - 10.1186/s12864-017-3938-5 [doi] LID - 545 AB - BACKGROUND: Clustered regularly-interspaced short palindromic repeats (CRISPR) screens are usually implemented in cultured cells to identify genes with critical functions. Although several methods have been developed or adapted to analyze CRISPR screening data, no single specific algorithm has gained popularity. Thus, rigorous procedures are needed to overcome the shortcomings of existing algorithms. METHODS: We developed a Permutation-Based Non-Parametric Analysis (PBNPA) algorithm, which computes p-values at the gene level by permuting sgRNA labels, and thus it avoids restrictive distributional assumptions. Although PBNPA is designed to analyze CRISPR data, it can also be applied to analyze genetic screens implemented with siRNAs or shRNAs and drug screens. RESULTS: We compared the performance of PBNPA with competing methods on simulated data as well as on real data. PBNPA outperformed recent methods designed for CRISPR screen analysis, as well as methods used for analyzing other functional genomics screens, in terms of Receiver Operating Characteristics (ROC) curves and False Discovery Rate (FDR) control for simulated data under various settings. Remarkably, the PBNPA algorithm showed better consistency and FDR control on published real data as well. CONCLUSIONS: PBNPA yields more consistent and reliable results than its competitors, especially when the data quality is low. R package of PBNPA is available at: https://cran.r-project.org/web/packages/PBNPA/ . FAU - Jia, Gaoxiang AU - Jia G AD - Department of Statistical Science, Southern Methodist University, Dallas, TX, 75205, USA. AD - Quantitative Biomedical Research Center, Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA. FAU - Wang, Xinlei AU - Wang X AD - Department of Statistical Science, Southern Methodist University, Dallas, TX, 75205, USA. swang@smu.edu. FAU - Xiao, Guanghua AU - Xiao G AUID- ORCID: 0000-0001-9387-9883 AD - Quantitative Biomedical Research Center, Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA. guanghua.xiao@utsouthwestern.edu. AD - Department of Bioinformatics, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA. guanghua.xiao@utsouthwestern.edu. AD - Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA. guanghua.xiao@utsouthwestern.edu. LA - eng GR - R15 GM113157/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20170719 PL - England TA - BMC Genomics JT - BMC genomics JID - 100965258 RN - 0 (RNA, Guide, CRISPR-Cas Systems) SB - IM MH - *Algorithms MH - Clustered Regularly Interspaced Short Palindromic Repeats/*genetics MH - RNA, Guide, CRISPR-Cas Systems/genetics MH - Statistics, Nonparametric PMC - PMC5518132 OTO - NOTNLM OT - False discovery rate OT - Functional genomics OT - Negative selection OT - Next generation sequencing OT - Positive selection OT - RNA interference COIS- ETHICS APPROVAL AND CONSENT TO PARTICIPATE: Not applicable. CONSENT FOR PUBLICATION: Not applicable. COMPETING INTERESTS: The authors declare that they have no competing interests. PUBLISHER'S NOTE: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. EDAT- 2017/07/21 06:00 MHDA- 2018/03/14 06:00 PMCR- 2017/07/19 CRDT- 2017/07/21 06:00 PHST- 2017/01/19 00:00 [received] PHST- 2017/07/12 00:00 [accepted] PHST- 2017/07/21 06:00 [entrez] PHST- 2017/07/21 06:00 [pubmed] PHST- 2018/03/14 06:00 [medline] PHST- 2017/07/19 00:00 [pmc-release] AID - 10.1186/s12864-017-3938-5 [pii] AID - 3938 [pii] AID - 10.1186/s12864-017-3938-5 [doi] PST - epublish SO - BMC Genomics. 2017 Jul 19;18(1):545. doi: 10.1186/s12864-017-3938-5.