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基因组学可解释的机器学习。

Interpretable machine learning for genomics.

机构信息

Department of Statistical Science, University College London, London, UK.

出版信息

Hum Genet. 2022 Sep;141(9):1499-1513. doi: 10.1007/s00439-021-02387-9. Epub 2021 Oct 20.

Abstract

High-throughput technologies such as next-generation sequencing allow biologists to observe cell function with unprecedented resolution, but the resulting datasets are too large and complicated for humans to understand without the aid of advanced statistical methods. Machine learning (ML) algorithms, which are designed to automatically find patterns in data, are well suited to this task. Yet these models are often so complex as to be opaque, leaving researchers with few clues about underlying mechanisms. Interpretable machine learning (iML) is a burgeoning subdiscipline of computational statistics devoted to making the predictions of ML models more intelligible to end users. This article is a gentle and critical introduction to iML, with an emphasis on genomic applications. I define relevant concepts, motivate leading methodologies, and provide a simple typology of existing approaches. I survey recent examples of iML in genomics, demonstrating how such techniques are increasingly integrated into research workflows. I argue that iML solutions are required to realize the promise of precision medicine. However, several open challenges remain. I examine the limitations of current state-of-the-art tools and propose a number of directions for future research. While the horizon for iML in genomics is wide and bright, continued progress requires close collaboration across disciplines.

摘要

高通量技术,如下一代测序,使生物学家能够以前所未有的分辨率观察细胞功能,但生成的数据集太大且复杂,如果没有先进的统计方法的帮助,人类将无法理解。机器学习 (ML) 算法旨在自动发现数据中的模式,非常适合这项任务。然而,这些模型通常非常复杂,以至于不透明,让研究人员几乎无法了解潜在的机制。可解释机器学习 (iML) 是计算统计学中一个新兴的子学科,致力于使 ML 模型的预测对最终用户更具可理解性。本文是对 iML 的一个温和而批判的介绍,重点是基因组应用。我定义了相关概念,激发了主要的方法,并提供了现有方法的简单分类。我调查了基因组学中 iML 的最新示例,展示了这些技术如何越来越多地融入研究工作流程。我认为,要实现精准医疗的承诺,就需要 iML 解决方案。然而,仍有几个悬而未决的挑战。我检查了当前最先进工具的局限性,并为未来的研究提出了一些方向。虽然基因组学中 iML 的前景广阔且光明,但持续进展需要跨学科的密切合作。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ce8/9360112/9ef517a697a9/439_2021_2387_Fig1_HTML.jpg

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