小柯机器人

机器学习实现灵敏病毒诊断的设计
2022-03-06 18:19

美国哈佛大学Pardis C. Sabeti、Hayden C. Metsky等研究人员合作利用机器学习实现灵敏病毒诊断的设计。这一研究成果于2022年3月3日在线发表在国际学术期刊《自然—生物技术》上。

研究人员表示,基于核酸的病毒诊断设计通常遵循启发式规则,为了应对病毒的变异,重点关注基因组的保守区域。相反,一个设计过程可以利用对目标及其变异体的敏感性的学习模型直接优化诊断效果。
 
为了实现这一目标,研究人员筛选了19209个诊断目标对,集中于基于CRISPR的诊断,并训练了一个深度神经网络来准确预测诊断的读出量。研究人员将这一模型与组合优化结合起来,在病毒基因组变异的全部范围内实现灵敏度最大化。研究人员引入了自动设计系统ADAPT,并利用它在2小时内为大多数脊椎动物感染的病毒物种设计了诊断方法,并在24小时内为所有物种设计了诊断方法,只有三种除外。
 
研究人员在实验中发现,ADAPT的设计在谱系层面上是敏感和特异的,并且在病毒的各种变异中实现较低的检测极限。这一策略为病原体检测提供了一个前瞻性的资源。
 
附:英文原文
 
Title: Designing sensitive viral diagnostics with machine learning

Author: Metsky, Hayden C., Welch, Nicole L., Pillai, Priya P., Haradhvala, Nicholas J., Rumker, Laurie, Mantena, Sreekar, Zhang, Yibin B., Yang, David K., Ackerman, Cheri M., Weller, Juliane, Blainey, Paul C., Myhrvold, Cameron, Mitzenmacher, Michael, Sabeti, Pardis C.

Issue&Volume: 2022-03-03

Abstract: Design of nucleic acid-based viral diagnostics typically follows heuristic rules and, to contend with viral variation, focuses on a genome’s conserved regions. A design process could, instead, directly optimize diagnostic effectiveness using a learned model of sensitivity for targets and their variants. Toward that goal, we screen 19,209 diagnostic–target pairs, concentrated on CRISPR-based diagnostics, and train a deep neural network to accurately predict diagnostic readout. We join this model with combinatorial optimization to maximize sensitivity over the full spectrum of a virus’s genomic variation. We introduce Activity-informed Design with All-inclusive Patrolling of Targets (ADAPT), a system for automated design, and use it to design diagnostics for 1,933 vertebrate-infecting viral species within 2hours for most species and within 24hours for all but three. We experimentally show that ADAPT’s designs are sensitive and specific to the lineage level and permit lower limits of detection, across a virus’s variation, than the outputs of standard design techniques. Our strategy could facilitate a proactive resource of assays for detecting pathogens.

DOI: 10.1038/s41587-022-01213-5

Source: https://www.nature.com/articles/s41587-022-01213-5

Nature Biotechnology:《自然—生物技术》,创刊于1996年。隶属于施普林格·自然出版集团,最新IF:68.164
官方网址:https://www.nature.com/nbt/
投稿链接:https://mts-nbt.nature.com/cgi-bin/main.plex


本期文章:《自然—生物技术》:Online/在线发表

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