A community effort to create standards for evaluating tumor subclonal reconstruction
AuthorSalcedo, A; Tarabichi, M; Espiritu, SMG; Deshwar, AG; David, M; Wilson, NM; Dentro, S; Wintersinger, JA; Liu, LY; Ko, M; ...
Source TitleNature Biotechnology
University of Melbourne Author/sCmero, Marek
AffiliationSir Peter MacCallum Department of Oncology
Document TypeJournal Article
CitationsSalcedo, A., Tarabichi, M., Espiritu, S. M. G., Deshwar, A. G., David, M., Wilson, N. M., Dentro, S., Wintersinger, J. A., Liu, L. Y., Ko, M., Sivanandan, S., Zhang, H., Zhu, K., Ou Yang, T. -H., Chilton, J. M., Buchanan, A., Lalansingh, C. M., P'ng, C., Anghel, C. V. ,... Zhu, H. (2020). A community effort to create standards for evaluating tumor subclonal reconstruction. NATURE BIOTECHNOLOGY, 38 (1), pp.97-+. https://doi.org/10.1038/s41587-019-0364-z.
Access StatusAccess this item via the Open Access location
Open Access URLAccepted version
Tumor DNA sequencing data can be interpreted by computational methods that analyze genomic heterogeneity to infer evolutionary dynamics. A growing number of studies have used these approaches to link cancer evolution with clinical progression and response to therapy. Although the inference of tumor phylogenies is rapidly becoming standard practice in cancer genome analyses, standards for evaluating them are lacking. To address this need, we systematically assess methods for reconstructing tumor subclonality. First, we elucidate the main algorithmic problems in subclonal reconstruction and develop quantitative metrics for evaluating them. Then we simulate realistic tumor genomes that harbor all known clonal and subclonal mutation types and processes. Finally, we benchmark 580 tumor reconstructions, varying tumor read depth, tumor type and somatic variant detection. Our analysis provides a baseline for the establishment of gold-standard methods to analyze tumor heterogeneity.
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