SeqClone: sequential Monte Carlo based inference of tumor subclones

Ogundijo, Oyetunji E.; Wang, Xiaodong

Tumor samples are heterogeneous. They consist of varying cell populations or subclones and each subclone is characterized with a distinct single nucleotide variant (SNV) profile. This explains the source of genetic heterogeneity observed in tumor sequencing data. To make precise prognosis and design effective therapy for cancer, ascertaining the subclonal composition of a tumor is of great importance.

In this paper, we propose a state-space formulation of the feature allocation model. This model is interpreted as the blind deconvolution of the expected variant allele fractions (VAFs). VAFs are deconvolved into a binary matrix of genotypes and a matrix of genotype proportions in the samples. Specifically, we consider a sequential construction of the genotype matrix which we model by Indian buffet process (IBP). We describe an efficient sequential Monte Carlo (SMC) algorithm, SeqClone, that jointly estimates the genotypes of subclones and their proportions in the samples. When compared to other methods for resolving tumor heterogeneity, SeqClone provides comparable and sometimes, better estimates of model parameters. By design, SeqClone conveniently handles any number of probed SNVs in the samples. In particular, we can analyze VAFs from newly probed SNVs to improve existing estimates, an attribute not present in existing solutions.

We show that the SMC algorithm for deconvolving VAFs from tumor sequencing data is a robust and promising alternative for explaining the observed genetic heterogeneity in tumor samples.


  • thumnail for 12859_2018_Article_2562.pdf 12859_2018_Article_2562.pdf application/pdf 1.37 MB Download File

Also Published In

BMC Bioinformatics

More About This Work

Academic Units
Electrical Engineering
Published Here
April 16, 2019


Tumor heterogeneity, Bayesian model, Sequential Monte Carlo, Indian buffet process