학술논문

Using Transcriptional Signatures to Find Cancer Drivers with LURE.
Document Type
article
Source
Subject
Humans
Neoplasms
Computational Biology
Mutation
Machine Learning
Cancer
Genomics
Drivers
Gene Expression
Human Genome
Genetics
Language
Abstract
Cancer genome projects have produced multidimensional datasets on thousands of samples. Yet, depending on the tumor type, 5-50% of samples have no known driving event. We introduce a semi-supervised method called Learning UnRealized Events (LURE) that uses a progressive label learning framework and minimum spanning analysis to predict cancer drivers based on their altered samples sharing a gene expression signature with the samples of a known event. We demonstrate the utility of the method on the TCGA Pan-Cancer Atlas dataset for which it produced a high-confidence result relating 59 new connections to 18 known mutation events including alterations in the same gene, family, and pathway. We give examples of predicted drivers involved in TP53, telomere maintenance, and MAPK/RTK signaling pathways. LURE identifies connections between genes with no known prior relationship, some of which may offer clues for targeting specific forms of cancer. Code and Supplemental Material are available on the LURE website: https://sysbiowiki.soe.ucsc.edu/lure.