دورية أكاديمية

Mudskipper detects combinatorial RNA binding protein interactions in multiplexed CLIP data.

التفاصيل البيبلوغرافية
العنوان: Mudskipper detects combinatorial RNA binding protein interactions in multiplexed CLIP data.
المؤلفون: Her H; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Sanford Stem Cell Institute Innovation Center and Stem Cell Program, University of California, San Diego, La Jolla, CA 92093, USA; Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Bioinformatics and Systems Biology Graduate Program, University of California, San Diego, La Jolla, CA 92093, USA., Rothamel KL; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Sanford Stem Cell Institute Innovation Center and Stem Cell Program, University of California, San Diego, La Jolla, CA 92093, USA; Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA 92093, USA., Nguyen GG; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Sanford Stem Cell Institute Innovation Center and Stem Cell Program, University of California, San Diego, La Jolla, CA 92093, USA; Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA 92093, USA., Boyle EA; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Sanford Stem Cell Institute Innovation Center and Stem Cell Program, University of California, San Diego, La Jolla, CA 92093, USA; Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA 92093, USA., Yeo GW; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Sanford Stem Cell Institute Innovation Center and Stem Cell Program, University of California, San Diego, La Jolla, CA 92093, USA; Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: geneyeo@ucsd.edu.
المصدر: Cell genomics [Cell Genom] 2024 Jul 10; Vol. 4 (7), pp. 100603. Date of Electronic Publication: 2024 Jul 01.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Elsevier, Inc Country of Publication: United States NLM ID: 9918284260106676 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2666-979X (Electronic) Linking ISSN: 2666979X NLM ISO Abbreviation: Cell Genom Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [New York] : Elsevier, Inc., [2021]-
مواضيع طبية MeSH: RNA-Binding Proteins*/metabolism , RNA-Binding Proteins*/genetics, Humans ; Immunoprecipitation/methods ; Binding Sites ; Software ; Computational Biology/methods ; RNA/metabolism ; RNA/genetics ; Protein Binding
مستخلص: The uncovering of protein-RNA interactions enables a deeper understanding of RNA processing. Recent multiplexed crosslinking and immunoprecipitation (CLIP) technologies such as antibody-barcoded eCLIP (ABC) dramatically increase the throughput of mapping RNA binding protein (RBP) binding sites. However, multiplex CLIP datasets are multivariate, and each RBP suffers non-uniform signal-to-noise ratio. To address this, we developed Mudskipper, a versatile computational suite comprising two components: a Dirichlet multinomial mixture model to account for the multivariate nature of ABC datasets and a softmasking approach that identifies and removes non-specific protein-RNA interactions in RBPs with low signal-to-noise ratio. Mudskipper demonstrates superior precision and recall over existing tools on multiplex datasets and supports analysis of repetitive elements and small non-coding RNAs. Our findings unravel splicing outcomes and variant-associated disruptions, enabling higher-throughput investigations into diseases and regulation mediated by RBPs.
Competing Interests: Declaration of interests G.W.Y. is a co-founder, member of the Board of Directors, on the SAB, equity holder, and paid consultant for Locanabio (until 12/31/2023) and Eclipse BioInnovations. G.W.Y. is a visiting professor at the National University of Singapore. G.W.Y.’s interests have been reviewed and approved by the University of California, San Diego in accordance with its conflict-of-interest policies.
(Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
معلومات مُعتمدة: R01 HG004659 United States HG NHGRI NIH HHS; U24 HG009889 United States HG NHGRI NIH HHS
فهرسة مساهمة: Keywords: CLIP; RNA; RNA-binding proteins; deep learning; gene regulation; splicing; transcriptomics; variant interpretation
المشرفين على المادة: 0 (RNA-Binding Proteins)
63231-63-0 (RNA)
تواريخ الأحداث: Date Created: 20240702 Date Completed: 20240711 Latest Revision: 20240714
رمز التحديث: 20240714
DOI: 10.1016/j.xgen.2024.100603
PMID: 38955188
قاعدة البيانات: MEDLINE
الوصف
تدمد:2666-979X
DOI:10.1016/j.xgen.2024.100603