학술논문

SUITOR: Selecting the number of mutational signatures through cross-validation
Research Article
Document Type
Report
Source
PLoS Computational Biology. April 4, 2022, Vol. 18 Issue 4, e1009309
Subject
United States
Language
English
ISSN
1553-734X
Abstract
Author(s): Donghyuk Lee 1, Difei Wang 2, Xiaohong R. Yang 2, Jianxin Shi 2, Maria Teresa Landi 2, Bin Zhu 2,* This is a PLOS Computational Biology Methods paper. Background [...]
For de novo mutational signature analysis, the critical first step is to decide how many signatures should be expected in a cancer genomics study. An incorrect number could mislead downstream analyses. Here we present SUITOR (Selecting the nUmber of mutatIonal signaTures thrOugh cRoss-validation), an unsupervised cross-validation method that requires little assumptions and no numerical approximations to select the optimal number of signatures without overfitting the data. In vitro studies and in silico simulations demonstrated that SUITOR can correctly identify signatures, some of which were missed by other widely used methods. Applied to 2,540 whole-genome sequenced tumors across 22 cancer types, SUITOR selected signatures with the smallest prediction errors and almost all signatures of breast cancer selected by SUITOR were validated in an independent breast cancer study. SUITOR is a powerful tool to select the optimal number of mutational signatures, facilitating downstream analyses with etiological or therapeutic importance.