qpure: A tool to estimate tumor cellularity from genome-wide single-nucleotide polymorphism profiles.
Tumour cellularity, the relative proportion of tumour and normal cells in a sample, affects the sensitivity of mutation detection, copy number analysis, cancer gene expression and methylation profiling. Tumour cellularity is traditionally estimated by pathological review of sectioned specimens; however this method is both subjective and prone to error due to heterogeneity within lesions and cellularity differences between the sample viewed during pathological review and tissue used for research purposes. In this paper we describe a statistical model to estimate tumour cellularity from SNP array profiles of paired tumour and normal samples using shifts in SNP allele frequency at regions of loss of heterozygosity (LOH) in the tumour. We also provide qpure, a software implementation of the method. Our experiments showed that there is a medium correlation 0.42 ([Formula: see text]-value=0.0001) between tumor cellularity estimated by qpure and pathology review. Interestingly there is a high correlation 0.87 ([Formula: see text]-value [Formula: see text] 2.2e-16) between cellularity estimates by qpure and deep Ion Torrent sequencing of known somatic KRAS mutations; and a weaker correlation 0.32 ([Formula: see text]-value=0.004) between IonTorrent sequencing and pathology review. This suggests that qpure may be a more accurate predictor of tumour cellularity than pathology review. qpure can be downloaded from https://sourceforge.net/projects/qpure/.
Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, St Lucia, Brisbane, Queensland, Australia. s.song@imb.uq.edu.au
Sarah
S
Song
Katia
K
Nones
David
D
Miller
Ivon
I
Harliwong
Karin S
KS
Kassahn
Mark
M
Pinese
Marina
M
Pajic
Anthony J
AJ
Gill
Amber L
AL
Johns
Matthew
M
Anderson
Oliver
O
Holmes
Conrad
C
Leonard
Darrin
D
Taylor
Scott
S
Wood
Qinying
Q
Xu
Felicity
F
Newell
Mark J
MJ
Cowley
Jianmin
J
Wu
Peter
P
Wilson
Lynn
L
Fink
Andrew V
AV
Biankin
Nic
N
Waddell
Sean M
SM
Grimmond
John V
JV
Pearson
D000465:Algorithms; D045744:Cell Line, Tumor; D019295:Computational Biology / Q000379:methods*; D005091:Exons; D005786:Gene Expression Regulation; D005787:Gene Frequency; D055106:Genome-Wide Association Study; D006801:Humans; D019656:Loss of Heterozygosity; D008957:Models, Genetic; D015233:Models, Statistical; D009154:Mutation; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D012044:Regression Analysis; D017422:Sequence Analysis, DNA; D012984:Software