دورية أكاديمية
Mudskipper detects combinatorial RNA binding protein interactions in multiplexed CLIP data.
العنوان: | Mudskipper detects combinatorial RNA binding protein interactions in multiplexed CLIP data. |
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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 |
تدمد: | 2666-979X |
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DOI: | 10.1016/j.xgen.2024.100603 |