A novel framework for analyzing somatic copy number aberrations and tumor subclones for paired heterogeneous tumor samples

Abstract

Application of the Next generation sequencing (NGS) technology has demonstrated that most tumor samples exhibit intra-tumor heterogeneity. Here we proposed SAPPH (Somatic Aberrations Prediction for Paired Heterogeneous tumor samples), as a new method for estimating tumor somatic copy number aberrations as well as inferring tumor subclone proportions from heterogeneous tumor sequencing data. This method is based on CBS and local proportion clustering strategy. When SAPPH is applied on simulated tumor samples, the agreement between the results analyzed by SAPPH and the sequencing signals suggests that SAPPH can find the solution to best fit the signal distributions. We benchmark the performance of SAPPH and show that it outperforms existing method in estimating tumor copy number aberrations.

Keywords: Intra-tumor heterogeneity; NGS; copy number aberration; proportion; tumor subclone.