Interpreting human genetic variation at atomic resolution

Michael T. Zimmermann

doi:10.1038/s41588-026-02763-z

2026-09-21

PRE

Michael T. Zimmermann *

Raúl Urrutia *

DOI：10.1038/s41588-026-02763-z

原文链接

原文求助

摘要

En 中文

临床测序和大型的国家及国际基因组学计划的广泛应用已使基因组医学发生变革。这些努力促成了新的诊断测试和用于处理测序衍生信息的计算工具，但许多变异的解释仍有限。与此同时，在过去的二十年中，计算结构基因组学（CSG）作为一种补充方法应运而生，它通过利用基因产物及其在蛋白质、DNA、RNA和小分子生物分子复合物中的组织模型，将研究重点从静态遗传注释转向动态、机制性解释。在这篇观点文章中，我们重点阐述了CSG如何通过整合序列信息、基序、结构域、分子结构、分子动力学模拟、多组学数据注释以及人工智能驱动的工具，从而实现对个体间遗传变异功能的全面和机制性理解。这些先进技术能够以原子分辨率预测变异的影响，并支持根据其功能障碍机制进行同时分类。本文讨论了计算结构基因组学，这是一个将遗传变异与其在细胞环境中的三维分子结构、动态和功能相联系的概念框架，旨在解释其机制。

期刊

Nature Genetics

IF:

论文数:

780

被引数:

241

机构

medical college of wisconsin

学者数:

1.7W

论文数: 1.3W

被引数: 9

引用论文

Structure-Based Functional Design of Drugs: From Target to Lead Compound

Methods in Molecular Biology

IF0

2011-10-21

OAAI

Amy C. Anderson

Genotype and phenotype in 18 Chinese patients with Coffin‐Siris syndrome

American Journal of Medical Genetics Part A

IF0

2021-03-26

PREAI

Shirley S. W. Cheng; Ho‐Ming Luk; Myth Tsz‐Shun Mok; Sha‐Sha Leung; Ivan F. M. Lo

Coffin–Siris syndrome is a SWI/SNF complex disorder

Clinical Genetics

IF0

2013-07-23

PREAI

Y. Tsurusaki; N. Okamoto; H. Ohashi; S. Mizuno; N. Matsumoto; Y. Makita; M. Fukuda; B. Isidor; J. Perrier; S. Aggarwal; A.B. Dalal; A. Al‐Kindy; J. Liebelt; D. Mowat; M. Nakashima; H. Saitsu; N. Miyake; N. Matsumoto

Molecular dynamics simulations of biomolecules 生物分子的分子动力学模拟

Nature Structural Biology

IF0

2002-09-01

PREAI

Martin Karplus; J. Andrew McCammon

Variation Interpretation Predictors: Principles, Types, Performance, and Choice

HUMAN MUTATION

IF3.7

2016-04-15

OAAI

Niroula, Abhishek; Vihinen, Mauno

Myosin Sequestration Regulates Sarcomere Function, Cardiomyocyte Energetics, and Metabolism, Informing the Pathogenesis of Hypertrophic Cardiomyopathy 肌球蛋白隔离调节肌节功能，心肌细胞能量学和代谢，为肥厚型心肌病的发病机理提供信息

CIRCULATION

IF38.6

2020-03-10

188

OAAI

Toepfer, Christopher N.; Garfinkel, Amanda C.; Venturini, Gabriela; Wakimoto, Hiroko; Repetti, Giuliana; Alamo, Lorenzo; Sharma, Arun; Agarwal, Radhika; Ewoldt, Jourdan F.; Cloonan, Paige; Letendre, Justin; Lun, Mingyue; Olivotto, Iacopo; Colan, Steve; Ashley, Euan; Jacoby, Daniel; Michels, Michelle; Redwood, Charles S.; Watkins, Hugh C.; Day, Sharlene M.; Staples, James F.; Padron, Raul; Chopra, Anant; Ho, Carolyn Y.; Chen, Christopher S.; Pereira, Alexandre C.; Seidman, Jonathan G.; Seidman, Christine E.

Cryo-EM in molecular and cellular biology

MOLECULAR CELL

IF16.6

2022-01-01

OAAI

Saibil, Helen R.

DNA language model GROVER learns sequence context in the human genome DNA语言模型GROVER学习人类基因组中的序列上下文

NATURE MACHINE INTELLIGENCE

IF23.9

2024-07-23

OAAI

Sanabria, Melissa; Hirsch, Jonas; Joubert, Pierre M.; Poetsch, Anna R.