Clonality Inference from Single Tumor Samples Using Low Coverage Sequence Data
Inference of intra-tumor heterogeneity can provide valuable insight into cancer evolution. Somatic mutations detected by sequencing can help estimate the purity of a tumor sample and reconstruct its subclonal composition. While several methods have been developed to infer intra-tumor heterogeneity, the majority of these tools rely on variant allele frequencies as estimated via ultra-deep sequencing from multiple samples of the same tumor. In practice, obtaining sequencing data from a large number of samples per patient is only feasible in a few cancer types such as liquid tumors, or in rare cases involving solid tumors selected for research. We introduce CTPsingle, which aims to infer the subclonal composition using low-coverage sequencing data from a single tumor sample. We show that CTPsingle is able to infer the purity and the clonality of single-sample tumors with high accuracy even restricted to a coverage depth of \(\sim \)30x.
KeywordsIntra-tumor heterogeneity Cancer progression DNA sequencing
This project was funded by a Prostate Cancer Canada Movember Team grant and the Terry Fox Research Institute New Frontiers Program to CCC; NSERC Discovery Frontiers Grant on the Cancer Genome Collaboratory, Genome Canada Bioinformatics and Computational Biology Program Grant and NSERC Discovery Grant to SCS; NSERC CREATE (139277) fellowship and Vanier Canada Graduate Scholarship to SM.
- 9.Khursheed, M., Kolla, J., Kotapalli, V., Gupta, N., Gowrishankar, S., Uppin, S., Sastry, R., Koganti, S., Sundaram, C., Pollack, J., et al.: ARID1B, a member of the human SWI/SNF chromatin remodeling complex, exhibits tumour-suppressor activities in pancreatic cancer cell lines. Br. J. Cancer 108(10), 2056–2062 (2013)CrossRefGoogle Scholar
- 17.Schuh, A., Becq, J., Humphray, S., Alexa, A., Burns, A., Clifford, R., Feller, S.M., Grocock, R., Henderson, S., Khrebtukova, I., Kingsbury, Z., Luo, S., McBride, D., Murray, L., Menju, T., Timbs, A., Ross, M., Taylor, J., Bentley, D.: Monitoring chronic lymphocytic leukemia progression by whole genome sequencing reveals heterogeneous clonal evolution patterns. Blood 120(20), 4191–4196 (2012)CrossRefGoogle Scholar
- 18.Sengupta, S., Wang, J., Lee, J., Müller, P., Gulukota, K., Banerjee, A., Ji, Y.: Bayclone: Bayesian nonparametric inference of tumor subclones using NGS data. In: Pacific Symposium on Biocomputing, vol. 20, p. 467. World Scientific (2015)Google Scholar