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KIM, J.

Publications and source records attributed to KIM, J..

2 recordsLinked to original sources

Scaling computational genomics to millions of individuals with GPUs

Current genomics methods were designed to handle tens to thousands of samples, but will soon need to scale to millions to keep up with the pace of data and hypothesis generation in biomedical science. Moreover, costs associated with processing these growing datasets will become prohibitive without improving the computational efficiency and scalability of methods. Here, we show that recently developed machine-learning libraries (TensorFlow and PyTorch) facilitate implementation of genomics methods for GPUs and significantly accelerate computations. To demonstrate this, we re-implemented methods for two commonly performed computational genomics tasks: QTL mapping and Bayesian non-negative matrix factorization. Our implementations ran > 200 times faster than current CPU-based versions, and these analyses are [~]5-10 fold cheaper on GPUs due to the vastly shorter runtimes. We anticipate that the accessibility of these libraries, and the improvements in run-time will lead to a transition to GPU-based implementations for a wide range of computational genomics methods.

genomics↗

Discovery and characterization of coding and non-coding driver mutations in more than 2,500 whole cancer genomes

Discovery of cancer drivers has traditionally focused on the identification of protein-coding genes. Here we present a comprehensive analysis of putative cancer driver mutations in both protein-coding and non-coding genomic regions across >2,500 whole cancer genomes from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We developed a statistically rigorous strategy for combining significance levels from multiple driver discovery methods and demonstrate that the integrated results overcome limitations of individual methods. We combined this strategy with careful filtering and applied it to protein-coding genes, promoters, untranslated regions (UTRs), distal enhancers and non-coding RNAs. These analyses redefine the landscape of non-coding driver mutations in cancer genomes, confirming a few previously reported elements and raising doubts about others, while identifying novel candidate elements across 27 cancer types. Novel recurrent events were found in the promoters or 5UTRs of TP53, RFTN1, RNF34, and MTG2, in the 3UTRs of NFKBIZ and TOB1, and in the non-coding RNA RMRP. We provide evidence that the previously reported non-coding RNAs NEAT1 and MALAT1 may be subject to a localized mutational process. Perhaps the most striking finding is the relative paucity of point mutations driving cancer in non-coding genes and regulatory elements. Though we have limited power to discover infrequent non-coding drivers in individual cohorts, combined analysis of promoters of known cancer genes show little excess of mutations beyond TERT.

genomics↗