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发布变异效应预测器的指南。

Guidelines for releasing a variant effect predictor.

作者信息

Livesey Benjamin J, Badonyi Mihaly, Dias Mafalda, Frazer Jonathan, Kumar Sushant, Lindorff-Larsen Kresten, McCandlish David M, Orenbuch Rose, Shearer Courtney A, Muffley Lara, Foreman Julia, Glazer Andrew M, Lehner Ben, Marks Debora S, Roth Frederick P, Rubin Alan F, Starita Lea M, Marsh Joseph A

机构信息

MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK.

Centre for Genomic Regulation (CRG),The Barcelona Institute of Science and Technology, Barcelona, Spain.

出版信息

ArXiv. 2024 Apr 16:arXiv:2404.10807v1.

Abstract

Computational methods for assessing the likely impacts of mutations, known as variant effect predictors (VEPs), are widely used in the assessment and interpretation of human genetic variation, as well as in other applications like protein engineering. Many different VEPs have been released to date, and there is tremendous variability in their underlying algorithms and outputs, and in the ways in which the methodologies and predictions are shared. This leads to considerable challenges for end users in knowing which VEPs to use and how to use them. Here, to address these issues, we provide guidelines and recommendations for the release of novel VEPs. Emphasising open-source availability, transparent methodologies, clear variant effect score interpretations, standardised scales, accessible predictions, and rigorous training data disclosure, we aim to improve the usability and interpretability of VEPs, and promote their integration into analysis and evaluation pipelines. We also provide a large, categorised list of currently available VEPs, aiming to facilitate the discovery and encourage the usage of novel methods within the scientific community.

摘要

用于评估突变可能影响的计算方法,即变异效应预测器(VEP),广泛应用于人类遗传变异的评估和解释,以及蛋白质工程等其他应用中。迄今为止,已经发布了许多不同的VEP,它们的基础算法和输出、方法和预测的共享方式存在巨大差异。这给终端用户在了解使用哪些VEP以及如何使用它们方面带来了相当大的挑战。在此,为解决这些问题,我们提供了关于发布新型VEP的指南和建议。我们强调开源可用性、透明的方法、清晰的变异效应评分解释、标准化量表、可访问的预测以及严格的训练数据披露,旨在提高VEP的可用性和可解释性,并促进它们融入分析和评估流程。我们还提供了一份庞大的、分类的当前可用VEP列表,旨在促进科学界对新方法的发现并鼓励使用这些新方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/51ed/11065047/91e10fcb84fc/nihpp-2404.10807v1-f0001.jpg

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