St. Jude Cloud—a Pediatric Cancer Genomic Data Sharing Ecosystem

Abstract

Effective data sharing is key to accelerating research that will improve the precision of diagnoses, efficacy of treatments and long term survival of pediatric cancer and other childhood catastrophic diseases. We present St. Jude Cloud (https://www.stjude.cloud), a cloud based data sharing ecosystem developed via collaboration between St. Jude Children's Research Hospital, DNAnexus, and Microsoft, for accessing, analyzing and visualizing genomic data from >10,000 pediatric cancer patients, long term survivors of pediatric cancer and >800 pediatric sickle cell patients. Harmonized genomic data totaling 1.25 petabyes on St. Jude Cloud include 12,104 whole genomes, 7,697 whole exomes and 2,202 transcriptomes, which are freely available to researchers worldwide. The resource is expanding rapidly with regular data uploads from St. Jude's prospective clinical genomics programs, providing public access as soon as possible rather than holding data back until publication. Three interconnected apps within the St. Jude Cloud ecosystem Genomics Platform, Pediatric Cancer Knowledgebase (PeCan) and Visualization Community provide a unique experience for simultaneously performing advanced data analysis in the cloud and enhancing the pediatric cancer knowledgebase. We demonstrate the value of the St. Jude Cloud ecosystem through use cases that classify 48 pediatric cancer subtypes by gene expression profiling and map mutational signatures across 35 subtypes of pediatric cancer.

CD99 antibody disrupts T-cell acute lymphoblastic leukemia adhesion to meningeal cells and attenuates chemoresistance

“…Finally, we confirmed prior work demonstrating CD99 expression in leukemia cells. We used the St. Jude PeCan Data Portal 17 to assess CD99 mRNA expression in > 1000 pediatric hematologic malignancy cases and found CD99 is more highly expressed in pediatric T-cell leukemia than either B-cell leukemia or AML (Fig. 1 e).…”

The chemotherapeutic CX-5461 primarily targets TOP2B and exhibits selective activity in high-risk neuroblastoma

“…GTEx data were obtained from the GTEx data portal (www.gtexportal.org), TCGA data from the Genomics Data Commons, paired relapse data was obtained from TARGET 67 and data from paired primary tumor and metastatic sites was obtained from 42 . Paired patient tumor – PDX gene expression data for our 2 xenografts was obtained from the St. Jude Cloud 68 . When comparing the expression of TOP2B , we also normalized these gene expression data by calculating their log 2 fold-change relative to housekeeping genes ACTIN and GAPDH , which are treated as negative controls whose expression is not expected to vary, thus mitigating the effect of gene expression differences that would be expected to arise due to dataset-specific effects.…”

Preclinical efficacy of prexasertib in acute lymphoblastic leukemia

“…This includes multiple cancers, including ovarian, for which CHK1 inhibition has shown clinical efficacy or is undergoing clinical testing 2 . To extend these analyses beyond cell lines we then used the St Jude PeCan Data Portal to assess CHK1 mRNA expression in 23 different cancers 8 . CHK1 mRNA was more highly expressed in haematologic malignancies, and specifically T‐ and B‐ALL, relative to solid tumours (Supplemental Figure S1D).…”

“…2 To extend these analyses beyond cell lines we then used the St Jude PeCan Data Portal to assess CHK1 mRNA expression in 23 different cancers. 8 CHK1 mRNA was more highly expressed in haematologic malignancies, and specifically T-and B-ALL, relative to solid tumours (Supplemental Figure S1D). Similar to the CCLE data, CHK1 mRNA levels were higher in T-than B-ALL.…”