DNA sequencing to identify variants is becoming increasingly valuable in clinical settings; including matching patients to approved targeted therapies, immunotherapies, and/or clinical trials. However, accurate calling of genetic variants from sequencing still remains challenging. With little corroboration between the different tools available, patients are at risk of being treated with therapies that are unsuitable for their cancer.
Here we present a novel machine learning based method for the accurate identification of somatic variants in cancer patient tumour samples, with a neural network architecture from encoded raw sequencing read information of tumour/normal sample pairings into an image, enabling it to classify whether a variant is germline, somatic, or sequencing error. The model was trained and tested on in-silico spike-in data using bam-surgeon, and then validated on a multi-cancer and multi-center dataset and benchmarked against industry standard variant callers.
The approach, called somaticNET, outperforms existing industry standard tools in sensitivity and specificity, achieving an AUROC of ∼1.00 on the bam-surgeon dataset and an AUROC of ∼0.99 on the multi-cancer multicenter dataset. The model also works faster than other variant callers, in minutes compared to hours.
Using the power of machine learning for accurate somatic variant calling can improve patient matching to approved therapies and clinical trials, thus ensuring patients are given the right therapy at the right time to treat their cancer.
The authors.
Cambridge Cancer Genomics.
G. Dubourg-Felonneau: Shareholder / Stockholder / Stock options, Full / Part-time employment: Cambridge Cancer Genomics. D. Rebergen: Shareholder / Stockholder / Stock options, Full / Part-time employment: Cambridge Cancer Genomics. C. Parsons: Shareholder / Stockholder / Stock options, Full / Part-time employment: Cambridge Cancer Genomics. H. Thompson: Shareholder / Stockholder / Stock options, Full / Part-time employment: Cambridge Cancer Genomics. J.W. Cassidy: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment, Officer / Board of Directors: Cambridge Cancer Genomics. N. Patel: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment: Cambridge Cancer Genomics. H.W. Clifford: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment: Cambridge Cancer Genomics.