Tags:Next Generation Sequence Data Sets, Somatic Variant Detection and Tumor Phylogeny
Abstract:
We study the performance of a variant detection method that is based on a property of tumor phylogenetic tree. Our major contributions are two folds. First, we show the property of tumor phylogenetic tree: the total patterns of mutations are restricted if a multi-regional mutation profile follows a corresponding tumor phylogenetic tree, where a multi-regional mutation profile is a matrix in which predictions of somatic mutations at the corresponding tumor regions are listed. Second, we evaluate the lower and upper bounds of specificity and sensitivity of a phylogeny-based somatic variant detection method under several situations. In the evaluation, we conduct patient-wise variant detection from a noisy multi-regional mutation profile matrix for some genomic positions by utilizing the phylogenetic property; we assume that the phylogenetic information can be extracted from another mutation profile matrix that contains accurate candidates at different genomic positions from the noisy ones. From the evaluation, we find that higher sensitivity is not guaranteed in the phylogeny-based variant detection, but higher specificity is guaranteed for several cases. These findings indicate the tumor phylogeny gives more merit for variant detection based on erroneous long-read sequencers (e.g. Oxford nanopore sequencers) than that based on accurate short-read sequencers (e.g., Illumina sequencer).
Theoretical Foundation of the Performance of Phylogeny-Based Somatic Variant Detection