clonal tracking as quality control for mutational signature analysis

Christoffer Flensburg⁰, Ian Majewski¹
(0) WEHI
(1) Walter Eliza Hall Institute of Medical Research

Find me on Tues Nov 24th, 1:40-3pm AEDT in Remo, table 107

Abstract
High throughput sequencing of cancer samples is an incredibly sensitive assay that can reveal deep information about the dynamics of a cancer. Unfortunately, the high sensitivity to detect somatic mutations comes with a high sensitivity to noise. Sequencing data is frequently discarded due to quality and some issues can lead to false conclusions if not identified. Quality control is often the most important and difficult part of an analysis but rarely takes the spotlight in publications or presentation. However, good quality control can identify low quality samples to avoid false signals, or even remove noise to extract a robust signal from precious samples.

I will show that clonal tracking can be a valuable quality control tool for bulk sequencing data, even when phylogeny or clonal structure is not a primary research question. We analysed a dataset of multiple polyps from an MBD4 deficient individual and used clonal tracking to overcome FFPE artefacts as well as contamination from a different individual. We found a consistent pattern of mutation in APC, AMER1, BFXW7 in clones consistent with a SBS1 signature, as well as *RAS mutations in clones with a novel CA>AA signature.