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评估从结构数据中识别RNA结合蛋白足迹的新型计算方法。

Evaluation of novel computational methods to identify RNA-binding protein footprints from structural data.

作者信息

Mizrahi Orel, Corley Meredith, Feldman Ori, Fröhlking Thorben, Sun Lei, Ziesel Alison, Antczak Maciej, Bernetti Mattia, Elhajjajy Shaimae I, Huang Wenze, Nguyen Grady G, Park Samuel S, Perez Martell Raul I, Trinity Luke, Xu Kui, Zok Tomasz, Bussi Giovanni, Jabbari Hosna, Orenstein Yaron, Aviran Sharon, Meyer Michelle M, Yeo Gene W

机构信息

Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, California 92037, USA.

Institute for Genomic Medicine, University of California San Diego, La Jolla, California 92037, USA.

出版信息

RNA. 2025 Jul 16;31(8):1103-1124. doi: 10.1261/rna.080215.124.

Abstract

RNA-binding proteins (RBP) play diverse roles in mRNA processing and function. However, from thousands of RBPs encoded in the human genome, a detailed molecular understanding of their interactions with RNA is available only for a small fraction. In most cases, our knowledge of the combination of RNA sequence and structure required for specific RBP binding is insufficient for accurately predicting binding sites transcriptome-wide. In this context, the rapidly expanding collection of transcriptomic data sets that map distinct, yet intertwined posttranscriptional marks, such as RNA structure and RBP binding, presents an opportunity for integrative analysis to better characterize RBP binding. A grand challenge faced by our community is that relatively little information on the secondary structure context within and near RBP-binding sites has been gleaned from integrating such data sets, partially due to lack of suitable computational methods. To engage scientists from diverse backgrounds in addressing this gap, the RNA Society organized the RBP Footprint Grand Challenge in 2021, an international community effort to develop new methods or leverage existing ones for predicting RBP-binding sites through analysis of a growing volume of sequence, structure, and binding data and to experimentally validate select predictions. Here, we report the initiative, analyses, and methods developed by the participants, validation results, and five new in vivo binding data sets generated for validation. We hope our work will inspire additional innovation in computational methods, further utilization of available data resources, and future endeavors to engage the community in collaborating toward closing other critical data-analysis gaps.

摘要

RNA结合蛋白(RBP)在mRNA加工和功能中发挥着多种作用。然而,在人类基因组编码的数千种RBP中,目前仅对其中一小部分与RNA的相互作用有详细的分子层面了解。在大多数情况下,我们对于特定RBP结合所需的RNA序列和结构组合的认识,还不足以在全转录组范围内准确预测结合位点。在此背景下,快速扩充的转录组数据集描绘了不同但相互交织的转录后标记,如RNA结构和RBP结合,这为整合分析以更好地表征RBP结合提供了契机。我们这个领域面临的一个重大挑战是,通过整合这些数据集,从RBP结合位点及其附近的二级结构背景中获取的信息相对较少,部分原因是缺乏合适的计算方法。为了让来自不同背景的科学家参与解决这一差距,RNA协会在2021年组织了RBP足迹重大挑战,这是一项国际社会共同努力,旨在开发新方法或利用现有方法,通过分析越来越多的序列、结构和结合数据来预测RBP结合位点,并通过实验验证选定的预测结果。在这里,我们报告了参与者开展的计划、分析和开发的方法、验证结果以及为验证而生成的五个新的体内结合数据集。我们希望我们的工作能够激发计算方法方面的更多创新,进一步利用现有的数据资源,并鼓励未来社区共同努力弥合其他关键数据分析差距。

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