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2014 ; 30
(12
): i78-86
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A combinatorial approach for analyzing intra-tumor heterogeneity from
high-throughput sequencing data
#MMPMID24932008
Hajirasouliha I
; Mahmoody A
; Raphael BJ
Bioinformatics
2014[Jun]; 30
(12
): i78-86
PMID24932008
show ga
MOTIVATION: High-throughput sequencing of tumor samples has shown that most
tumors exhibit extensive intra-tumor heterogeneity, with multiple subpopulations
of tumor cells containing different somatic mutations. Recent studies have
quantified this intra-tumor heterogeneity by clustering mutations into
subpopulations according to the observed counts of DNA sequencing reads
containing the variant allele. However, these clustering approaches do not
consider that the population frequencies of different tumor subpopulations are
correlated by their shared ancestry in the same population of cells. RESULTS: We
introduce the binary tree partition (BTP), a novel combinatorial formulation of
the problem of constructing the subpopulations of tumor cells from the variant
allele frequencies of somatic mutations. We show that finding a BTP is an
NP-complete problem; derive an approximation algorithm for an optimization
version of the problem; and present a recursive algorithm to find a BTP with
errors in the input. We show that the resulting algorithm outperforms existing
clustering approaches on simulated and real sequencing data. AVAILABILITY AND
IMPLEMENTATION: Python and MATLAB implementations of our method are available at
http://compbio.cs.brown.edu/software/ .