A Pan-Cancer and Polygenic Bayesian Hierarchical Model for the Effect of Somatic Mutations on Survival

Sarah Samorodnitsky, Katherine A. Hoadley, Eric F. Lock

Research output: Contribution to journalArticlepeer-review

Abstract

We built a novel Bayesian hierarchical survival model based on the somatic mutation profile of patients across 50 genes and 27 cancer types. The pan-cancer quality allows for the model to “borrow” information across cancer types, motivated by the assumption that similar mutation profiles may have similar (but not necessarily identical) effects on survival across different tissues of origin or tumor types. The effect of a mutation at each gene was allowed to vary by cancer type, whereas the mean effect of each gene was shared across cancers. Within this framework, we considered 4 parametric survival models (normal, log-normal, exponential, and Weibull), and we compared their performance via a cross-validation approach in which we fit each model on training data and estimate the log-posterior predictive likelihood on test data. The log-normal model gave the best fit, and we investigated the partial effect of each gene on survival via a forward selection procedure. Through this we determined that mutations at TP53 and FAT4 were together the most useful for predicting patient survival. We validated the model via simulation to ensure that our algorithm for posterior computation gave nominal coverage rates. The code used for this analysis can be found at https://github.com/sarahsamorodnitsky/Pan-Cancer-Survival-Modeling.git, and the results are summarized at http://ericfrazerlock.com/surv_figs/SurvivalDisplay.html.

Original languageEnglish (US)
JournalCancer Informatics
Volume19
DOIs
StatePublished - 2020

Bibliographical note

Funding Information:
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the National Institutes of Health (NIH) National Cancer Institute (NCI) grant R21CA231214-01.

Publisher Copyright:
© The Author(s) 2020.

Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.

Keywords

  • Bayesian hierarchical modeling
  • The Cancer Genome Atlas
  • pan-cancer modeling
  • survival analysis

PubMed: MeSH publication types

  • Journal Article

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