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The Pediatric Brain Tumor Atlas (PBTA), created as a multi-center effort by the Children’s Brain Tumor Tissue Consortium (CBTTC) and Pacific Pediatric Neuro-Oncology Consortium (PNOC) and supported by the Gabriella Miller Kids First Data Resource Center (DRC), has the initial goal of comprehensively characterizing over 1,600 clinically annotated pediatric brain tumor samples and making the data publicly available to cancer researchers worldwide in near real time and without embargo. PBTA comprises comprehensive clinical data in addition to whole exome sequencing, whole genome sequencing (WGS), RNA sequencing (RNASeq), miRNA sequencing, and proteomics. To address the need to inform novel discovery and clinical implementation of genomic approaches for diagnostic/therapeutic purposes, PBTA utilizes the cloud-based research environment of the Gabriella Miller Kids First DRC to provide near real-time integration, dissemination, processing, and sharing of associated petabyte-scale harmonized data. The PBTA initiative leverages the DRC platform’s users to access their dbGAP approved use of TARGET and other pediatric cancer datasets hosted by NCI’s Cancer Genomics’ Cloud and Genomic Data Commons, allowing for cross-disease studies. Processed annotations is further enabled for the PBTA via PedcBioPortal, a data visualization/analysis application further integrating additional public and deposited datasets. In its first data release are over 30 different types of pediatric brain tumors representing over 1,000 subjects. This data is available on the Kids First DRC Portal and PedcBioPortal and users can seamlessly move between applications. Data types include those for matched tumor/normal samples, such as WGS, RNASeq, proteomics, longitudinal clinical data, imaging data (MRIs and radiology reports), histology slide images, and pathology reports. CBTTC/PNOC promote real-time data release and collaborative discovery via shared resources. The combination of cloud-based analytic platforms with data from both genomics and clinical practice serves to define a new paradigm for accelerated pediatric cancer translational research.

Gabriella Miller Kids First Pediatric Research Program (GMKF) is a nation-wide, multi-year initiative focused on the integration of large-scale clinically annotated genomic data for childhood cancers and structural birth defects supported by the NIH Common Fund. Awarded by GMKF, the Kids First Data Resource Center (DRC) is tasked to build infrastructure and workflows for data intaking, harmonization, integration and access authorization to empower collaborative discoveries across the GMKF and other integrated datasets. A key challenge for uniform analyses and empowered discovery of large-scale genomic data relates to the diverse genomic processing workflows and methods employed across the sequencing and bioinformatics community. The DRC genomic harmonization team aims to provide “analysis ready” datasets that are “functionally equivalent” across the Kids First datasets and other large-scale genomic data initiatives in order to accelerate the discovery process. Paired with the cloud-based workspace environments of the DRC, such harmonized dataset provide unprecedented opportunities for shared, reproducible discovery by a diverse, collaborative network of researchers. As such, DRC initial pipelines are developed with BWA-MEM alignment on genome build GRCh38 followed by the GATK best practices for germline variant calling and joint genotyping. Common Workflow Language (CWL) is used as the main workflow specification, while Docker technology has been applied to containerize all the tools used by the workflow. Our current workflows are tasked with data harmonization across a number of different experimental platforms including whole genome sequencing, exome sequencing, and RNA-seq. The data processing is done via CAVATICA, an Amazon Web Services (AWS) based cloud computing platform associated with the Kids First DRC Portal co-developed by Seven Bridges Genomics, where workflows feature scatter-gather parallelization and AWS resource optimization. By utilizing such a framework, the DRC team has harmonized over 10,000 WGS and 1,000 RNA-Seq samples across 12 study cohorts within 8 months. This dataset in its current release includes samples from 40 pediatric brain cancers as well as 8 childhood birth defects with the outcome of delivering 150TB harmonized CRAM and 60TB gVCF. With a highly optimized bioinformatics pipeline powered by an efficient cloud-based execution workflow, The DRC platform processes one genome in about 11 hours with an average compute cost of $15 for whole genome alignment and germline variant calling. Here we present our observed challenges and identified opportunities in the analysis and integration of multi-disease pediatric genomic data on a large scale. Citation Format: Yuankun Zhu, Miguel Brown, Batsal Devkota, Bailey Farrow, Bogdan Gavrilovic, Allison Heath, Kyle Hernandez, Avi Kelman, Parimala Killada, Meen Chul Kim, Daniel Kolbman, Mateusz Koptyra, Milan Kovacevic, Maarten Leerkes, Alex Lubneuski, Michele Mattioni, Pichai Raman, Adam Resnick, Nikola Skundric, Deanne Taylor, Junjun Zhang, Bo Zhang, Phillip B. Storm. Genomic harmonization of the Data Resource Center for Gabriella Miller Kids First Pediatric Research Program [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 2465.

The Pediatric Brain Tumor Atlas (PBTA) is a cloud-based, cross-platform, and data-rich collaborative effort to accelerate discoveries for therapeutic intervention in children diagnosed with brain tumors. Pediatric brain tumors are the leading cause of disease-related death in children and despite advances in therapy, morbidity and mortality rates remain poor. There have been large scale efforts to genomically profile these cancers in the past, however public access to the resulting datasets are limited at best. In contrast, the PBTA, created as a multi-center effort by Children’s Brain Tumor Tissue Consortium (CBTTC) and Pacific Pediatric Neuro-Oncology Consortium (PNOC), has a goal of characterizing over 1,600 pediatric brain tumor samples and making the data publicly available to cancer researchers world-wide. PBTA comprises comprehensive clinical data in addition to whole exome sequencing, whole genome sequencing (WGS), RNA sequencing (RNASeq), miRNA sequencing, and proteomics. To address the need to inform novel discovery and clinical implementation of genomic approaches for diagnostic/therapeutic purposes, PBTA utilizes a cloud-based scientific environment, the CAVATICA portal. CAVATICA provides near real-time integration, dissemination, processing, and sharing of associated PetaByte-sized data by leveraging Amazon Web Services and powerful genomic workflows. It also enables dbGaP approved users to access TCGA and other datasets hosted by NCI’s Cancer Genomics’ Cloud, allowing for cross-disease studies. While CAVATICA manages raw sequencing data, processed annotations and biospecimen querying is enabled for PBTA via PedcBioPortal, a data visualization/analysis application further integrating additional public and deposited datasets. PBTA data can further be accessed via the KidsFirst platform, which integrates both CAVATICA and PedcBioPortal, and allows for querying of cancer and non-cancer genomic data for subsequent analytics, visualization, and discovery. The 1st dataset release of PBTA occurred on September 10th, 2018. In this release there are over 30 different types of pediatric brain tumors representing over 1,000 subjects. This data is available on CAVATICA, KidsFirst, and PedcBioPortal and users can seamlessly move between applications. Data types include those for matched tumor/normal samples, such as WGS, RNASeq, proteomics, longitudinal clinical data, imaging data (MRIs and radiology reports), histology slide images, and pathology reports. CBTTC/PNOC promote real time data release with no embargo period, allowing PBTA to have is up-to-date data releases with no embargo. The combination of cloud-based analytic platforms such as KidsFirst/CAVATICA/PedcBioPortal with data from both genomics and clinical practice serves to define a new paradigm for pediatric cancer research and collaborative discovery. Citation Format: Yuankun Zhu, Yiran Guo, Allison P. Heath, Pichai Raman, Elizabeth Appert, Jennifer Mason, Bo Zhang, Karthik Kalletla, Miguel A. Brown, Natasha Singh, Bailey K. Farrow, Parimala Killada, Meen Chul Kim, Alex Felmeister, Mateusz P. Koptyra, Sabine Mueller, Michael Prados, Jena V. Lilly, Rishi Lulla, Adam C. Resnick, Javad Nazarian, Phillip B. Storm, Angela J. Waanders. The Pediatric Brain Tumor Atlas - Transforming the landscape of research [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 3667.