Abstract 3671: Visualize 10,000 whole-genomes from pediatric cancer patients on St. Jude Cloud
Authors: Zhou Xin , Mcleod Clay , Newman Scott , Wang Zhaoming , Rusch Michael , Birch Kirby , Macias Michael , Sunny Jobin , Wu Gang , Wang Jian , Sioson Edgar , Lei Shaohua , Michael Robert J. , Patel Aman , Edmonson Michael N. , Rice Stephen V. , Frantz Andrew , Suh Ed , Perry Keith , Wilson Carmen , Robinson Leslie L. , Yasui Yutaka , Nichols Kim E. , Armstrong Gregory T. , Downing James R. , Zhang Jinghui 
Published: August 2019

Abstract
Whole-genome sequencing (WGS) is invaluable for investigating genetic abnormalities contributing to the initiation, progression and long-term clinical outcome of pediatric cancer. St. Jude Cloud (https://www.stjude.cloud/) hosts 10,000 (10K) harmonized WGS samples generated from: 1) St. Jude/Washington University Pediatric Cancer Genome Project, 2) the Genomes for Kids Clinical Trial, 3) the St. Jude Lifetime Cohort Study, and 4) the Childhood Cancer Survivor Study. To enable on-the-cloud discovery and eliminate the need for data download, we developed GenomePaint, an interactive genomics browser, to explore the somatic and germline variants of the 10K genomes with rich annotation.
Germline variants in cancer predisposition genes were annotated for pathogenicity. Using GenomePaint, users can compare pathogenic variants from a locus of interest across multiple cancers or test for association of a germline variant with a specific cancer type on the fly. By matching germline variants to somatic mutation hotspots from www.cancerhotspots.org, we annotated potential germline mosaic mutations including IDH1 R132H, FBXW7 R465C, and KRAS A146T. For noncoding variants, we investigated overlap with ATAC and DNase peaks in 50 cancer cell lines along with transcription factor motif change predictions. These features will enable exploration of the functional impact of genetic variations with potential clinical status such as genetic risk for a specific cancer type, genetic association with age of onset, or development of subsequent malignancies for pediatric cancer survivors.
GenomePaint also provides an integrated view of somatic SNV/indel, copy number variation, loss-of-heterozygosity, structural variation, and gene fusion. These are shown together with tumor gene expression at the single tumor level. GenomePaint also presents allele-specific expression (ASE) and outlier expression as an indicator for assessing dysfunction of regulatory regions caused by genomic variants. Cloud-based on-the-fly ASE analysis is also available for user’s samples with paired DNA and RNA sequencing results. Such gene expression integration will drive novel insights about the functional aspects of somatic coding and noncoding mutations in pediatric cancer.
The innovative visualization of whole-genome sequencing data generated from 10K pediatric cancer patients on the St. Jude Cloud enables genomic discovery by scientists and clinicians through exploration of this unprecedented resource.
Citation Format: Xin Zhou, Clay Mcleod, Scott Newman, Zhaoming Wang, Michael Rusch, Kirby Birch, Michael Macias, Jobin Sunny, Gang Wu, Jian Wang, Edgar Sioson, Shaohua Lei, Robert J. Michael, Aman Patel, Michael N. Edmonson, Stephen V. Rice, Andrew Frantz, Ed Suh, Keith Perry, Carmen Wilson, Leslie L. Robinson, Yutaka Yasui, Kim E. Nichols, Gregory T. Armstrong, James R. Downing, Jinghui Zhang. Visualize 10,000 whole-genomes from pediatric cancer patients on St. Jude Cloud [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3671.