Abstract:DNA sequencing to identify genetic variants is becoming increasingly valuable in clinical settings. Assessment of variants in such sequencing data is commonly implemented through Bayesian heuristic algorithms. Machine learning has shown great promise in improving on these variant calls, but the input for these is still a standardized "pile-up" image, which is not always best suited. In this paper, we present a novel method for generating images from DNA sequencing data, which interlaces the human reference genome with personalized sequencing output, to maximize usage of sequencing reads and improve machine learning algorithm performance. We demonstrate the success of this in improving standard germline variant calling. We also furthered this approach to include somatic variant calling across tumor/normal data with Siamese networks. These approaches can be used in machine learning applications on sequencing data with the hope of improving clinical outcomes, and are freely available for noncommercial use at www.ccg.ai.