Patient-specific data fusion for cancer stratification and personalised treatment
File(s)gligorijevic.pdf (1.09 MB)
Published version
Author(s)
Gligorijević, V
Malod-Dognin, N
Pržulj, N
Type
Journal Article
Abstract
According to Cancer Research UK, cancer is a leading cause of death accounting for more than one in four of all deaths in 2011. The recent advances in experimental technologies in cancer research have resulted in the accumulation of large amounts of patient-specific datasets, which provide complementary information on the same cancer type. We introduce a versatile data fusion (integration) framework that can effectively integrate somatic mutation data, molecular interactions and drug chemical data to address three key challenges in cancer research: stratification of patients into groups having different clinical outcomes, prediction of driver genes whose mutations trigger the onset and development of cancers, and repurposing of drugs treating particular cancer patient groups. Our new framework is based on graph-regularised non-negative matrix tri-factorization, a machine learning technique for co-clustering heterogeneous datasets. We apply our framework on ovarian cancer data to simultaneously cluster patients, genes and drugs by utilising all datasets.We demonstrate superior performance of our method over the state-of-the-art method, Network-based Stratification, in identifying three patient subgroups that have significant differences in survival outcomes and that are in good agreement with other clinical data. Also, we identify potential new driver genes that we obtain by analysing the gene clusters enriched in known drivers of ovarian cancer progression. We validated the top scoring genes identified as new drivers through database search and biomedical literature curation. Finally, we identify potential candidate drugs for repurposing that could be used in treatment of the identified patient subgroups by targeting their mutated gene products. We validated a large percentage of our drug-target predictions by using other databases and through literature curation.
Date Issued
2016-01-04
Date Acceptance
2016-01-04
Citation
Proceedings of the Pacific Symposium on Biocomputing, 2016, 2016, pp.321-332
ISSN
2335-6936
Publisher
World Scientific
Start Page
321
End Page
332
Journal / Book Title
Proceedings of the Pacific Symposium on Biocomputing
Volume
2016
Copyright Statement
© 2016 World Scientific. Published by World Scientific Publishing Company and distributed under the terms of the Creative Commons Attribution (CC BY) 4.0 License.
License URL
Sponsor
Commission of the European Communities
Identifier
PII: 9789814749411_0030
Grant Number
278212
Publication Status
Published