The Annals of Applied Statistics

A Bayesian feature allocation model for tumor heterogeneity

Juhee Lee, Peter Müller, Kamalakar Gulukota, and Yuan Ji

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Abstract

We develop a feature allocation model for inference on genetic tumor variation using next-generation sequencing data. Specifically, we record single nucleotide variants (SNVs) based on short reads mapped to human reference genome and characterize tumor heterogeneity by latent haplotypes defined as a scaffold of SNVs on the same homologous genome. For multiple samples from a single tumor, assuming that each sample is composed of some sample-specific proportions of these haplotypes, we then fit the observed variant allele fractions of SNVs for each sample and estimate the proportions of haplotypes. Varying proportions of haplotypes across samples is evidence of tumor heterogeneity since it implies varying composition of cell subpopulations. Taking a Bayesian perspective, we proceed with a prior probability model for all relevant unknown quantities, including, in particular, a prior probability model on the binary indicators that characterize the latent haplotypes. Such prior models are known as feature allocation models. Specifically, we define a simplified version of the Indian buffet process, one of the most traditional feature allocation models. The proposed model allows overlapping clustering of SNVs in defining latent haplotypes, which reflects the evolutionary process of subclonal expansion in tumor samples.

Article information

Source
Ann. Appl. Stat., Volume 9, Number 2 (2015), 621-639.

Dates
Received: July 2014
Revised: January 2015
First available in Project Euclid: 20 July 2015

Permanent link to this document
https://projecteuclid.org/euclid.aoas/1437397104

Digital Object Identifier
doi:10.1214/15-AOAS817

Mathematical Reviews number (MathSciNet)
MR3371328

Zentralblatt MATH identifier
06499923

Keywords
Haplotypes feature allocation models Indian buffet process Markov chain Monte Carlo next-generation sequencing random binary matrices variant calling

Citation

Lee, Juhee; Müller, Peter; Gulukota, Kamalakar; Ji, Yuan. A Bayesian feature allocation model for tumor heterogeneity. Ann. Appl. Stat. 9 (2015), no. 2, 621--639. doi:10.1214/15-AOAS817. https://projecteuclid.org/euclid.aoas/1437397104


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