arrow
返回

An interpretable deep learning framework for genome-informed precision oncology

delete2024-07-11
delete0
PRE
AI
S
Shuangxia Ren
G
Gregory F. Cooper
L
Lujia Chen
X
Xinghua Lu *
DOI:10.1038/s42256-024-00866-ydelete
delete原文链接
delete原文求助
delete分享
delete收藏
摘要

摘要

En 中文
Cancers result from aberrations in cellular signalling systems, typically resulting from driver somatic genome alterations (SGAs) in individual tumours. Precision oncology requires understanding the cellular state and selecting medications that induce vulnerability in cancer cells under such conditions. To this end, we developed a computational framework consisting of two components: (1) a representation-learning component, which learns a representation of the cellular signalling systems when perturbed by SGAs and uses a biologically motivated and interpretable deep learning model, and (2) a drug-response prediction component, which predicts drug responses by leveraging the information of the cellular state of the cancer cells derived by the first component. Our cell-state-oriented framework notably improves the accuracy of predictions of drug responses compared to models using SGAs directly in cell lines. Moreover, our model performs well with real patient data. Importantly, our framework enables the prediction of responses to chemotherapy agents based on SGAs, thus expanding genome-informed precision oncology beyond molecularly targeted drugs. Precision oncology requires analysis of genomic alterations in cancer cells. Ren et al. develop an interpretable artificial intelligence framework that transforms somatic genomic alterations into representations of cellular signalling systems and accurately predicts cells' responses to anticancer drugs.
Keyword:
DRUG-SENSITIVITY
CANCER

期刊

Nature Machine Intelligence 封面图
Nature Machine Intelligence
IF:
23.9
论文数:
1.3K
被引数:
1.5W

机构

U
University of Pittsburgh
学者数:
4.5W
论文数: 3.6W
被引数: 7.1W
P
pennsylvania commonwealth system of higher education (pcshe)
学者数:
12.9W
论文数: 11.7W
被引数: 177
引用论文

引用论文

Polyneuropathy in Australian Outpatients with Type II Diabetes Mellitus
err1999-03-01
err0
PREAI
errCarolyn N de Wytt; Richard V Jackson; Gregory I Hockings; Julie M Joyner; Christopher R Strakosch
err分享
err收藏
Systematic pan-cancer analysis of mutation-treatment interactions using large real-world clinicogenomics data
err2022-06-30
err20
PREAI
errLiu, Ruishan; Rizzo, Shemra; Waliany, Sarah; Garmhausen, Marius Rene; Pal, Navdeep; Huang, Zhi; Chaudhary, Nayan; Wang, Lisa; Harbron, Chris; Neal, Joel; Copping, Ryan; Zou, James
err分享
err收藏
err分享
err收藏
err2002-01-01
err0
PREAI
errJavier Valls; Martin Kuhlmann; Keshab K. Parhi
err分享
err收藏
Testing for Impulsive Behavior: A Bootstrap Approach
err2001-04-01
err0
PREAI
errChristopher L. Brown; Abdelhak M. Zoubir
err分享
err收藏
err分享
err收藏
Dysfunctional KEAP1-NRF2 interaction in non-small-cell lung cancer
err2006-10-03
err1.0K
errOAAI
errSingh, Anju; Misra, Vikas; Thimmulappa, Rajesh K.; Lee, Hannah; Ames, Stephen; Hoque, Mohammad O.; Herman, James G.; Baylin, Stephen B.; Sidransky, David; Gabrielson, Edward; Brock, Malcolm V.; Biswal, Shyam
err分享
err收藏
学者 查看更多内容