Schill, Rudolf and Solbrig, Stefan and Wettig, Tilo and Spang, Rainer (2020) Modelling cancer progression using Mutual Hazard Networks. BIOINFORMATICS, 36 (1). pp. 241-249. ISSN 1367-4803, 1460-2059
Full text not available from this repository. (Request a copy)Abstract
Motivation Cancer progresses by accumulating genomic events, such as mutations and copy number alterations, whose chronological order is key to understanding the disease but difficult to observe. Instead, cancer progression models use co-occurrence patterns in cross-sectional data to infer epistatic interactions between events and thereby uncover their most likely order of occurrence. State-of-the-art progression models, however, are limited by mathematical tractability and only allow events to interact in directed acyclic graphs, to promote but not inhibit subsequent events, or to be mutually exclusive in distinct groups that cannot overlap. Results Here we propose Mutual Hazard Networks (MHN), a new Machine Learning algorithm to infer cyclic progression models from cross-sectional data. MHN model events by their spontaneous rate of fixation and by multiplicative effects they exert on the rates of successive events. MHN compared favourably to acyclic models in cross-validated model fit on four datasets tested. In application to the glioblastoma dataset from The Cancer Genome Atlas, MHN proposed a novel interaction in line with consecutive biopsies: IDH1 mutations are early events that promote subsequent fixation of TP53 mutations. Availability and implementation Implementation and data are available at https://github.com/RudiSchill/MHN. Supplementary information Supplementary data are available at Bioinformatics online.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | PATHWAYS; EVOLUTION; INFERENCE; EXCLUSIVITY; MUTATIONS; IDH1; |
| Subjects: | 500 Science > 530 Physics 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Institut für Funktionelle Genomik > Lehrstuhl für Statistische Bioinformatik (Prof. Spang) Physics > Institute of Theroretical Physics Physics > Institute of Theroretical Physics > Chair Professor Braun > Group Tilo Wettig |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 08 Apr 2021 09:17 |
| Last Modified: | 08 Apr 2021 09:17 |
| URI: | https://pred.uni-regensburg.de/id/eprint/45538 |
Actions (login required)
 |
View Item |
