Search

Pediatric central nervous system (CNS) cancers are the leading disease-related cause of death in children and there is urgent need for curative therapeutic strategies for these tumors. To address the urgency, Children’s Brain Tumor Network (CBTN) has advanced an open science model to accelerate the research discovery for pediatric brain tumors. In first phase of Open Pediatric Brain Tumor Atlas (OpenPBTA) effort CBTN together with Pacific Pediatric Neuro-Oncology Consortium (PNOC) with support of Gabriella Miller Kids First Data Resource Center (KFDRC) created and comprehensively characterized over 1000 clinically annotated pediatric brain tumors. In the second phase of the OpenPBTA effort, through resource awards and collaboration across KFDRC, the NCI Childhood Cancer Data Initiative (CCDI), NCI’s Clinical Proteomic Tumor Analysis Consortium (CPTAC), NCI Center for Cancer Research and additional partnered institutions and foundations, CBTN has expanded OpenPBTA to support high throughput molecular characterization for an additional 1900 pediatric brain tumor patients and their families. This includes the processing and characterization of over 8000 specimens across >50 brain tumor diagnoses. The cohort expansion builds on >1000 previously characterized samples with a portfolio of multimodal data including whole genome sequencing, RNA sequencing, miRNA sequencing, methylation sequencing, proteomics, lipidomics and/or metabolomics. Molecular data is linked to patient longitudinal clinical data, imaging data (MRIs and radiology reports), histology slide images, and pathology reports. To inform novel discovery and clinical implementation of genomic approaches for diagnostic/therapeutic purposes, the data is deposited the cloud-based research environment of the NCI’s CCDI and the KFDRC to provide near real-time integration, dissemination, processing, and sharing of associated petabyte-scale harmonized data. The approach leverages the DRC platform’s cloud-based computational environment in CAVATICA. Processed annotations are facilitated via CAVATICA-enabled shareable pipelines and can be explored through PedcBioPortal, a data visualization/analysis application further integrating additional public and deposited datasets. This expansion phase of OpenPBTA is released with no embargo period and provides one of the largest deeply characterized cohorts of pediatric brain tumor samples and associated clinical data for >3000 pediatric brain tumor patients. CBTN’s open-science, rapid-release model aims to advance novel biomarkers and therapeutic exploratory research, supporting new clinical trial development and accelerated discovery on behalf of changing the outcome for kids with brain tumors. Citation Format: Mateusz P. Koptyra, Komal Rahti, Yuankun Zhu, Bailey Farrow, Daniel Miller, Adam Kraya, Yiran Guo, Peter Madsen, Nicholas Van Kuren, Xiaoyan Huang, Miguel A. Brown, Jennifer L. Mason, Meen Chul Kim, Allison P. Heath, Brian M. Ennis, Bo Zhang, Jena V. Lilly, Jo Lynne Rokita, Christopher Friedman, Ximena P. Cuellar, Catherine A. Sullivan, Noel Coleman, Trang Duros, Thinh Q. Nguyen, Emmett C. Drake, Zeinab Helili, Beth A. Frenkel, Gerri R. Trooskin, Ariana Familiar, Karthik Viswanathan, Christopher M. Beck, Madison L. Hollawell, Valerie P. Baubet, Cassie Kline, Mariarita Santi, Tatiana S. Patton, Stephanie Stefankiewicz, Arya Kamnaa, Ryan A. Velasco, Dani Cardona, Phillip J. Storm, Adam C. Resnick, o/b/o Children's Brain Tumor Network. Expansion of the Pediatric Brain Tumor Atlas: Children's Brain Tumor Network, Kids First Data Resource and Childhood Cancer Data Initiative Open Science effort. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3566.

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 Gabriella Miller Kids First Pediatric Research Program launched the Kids First Pediatric Data Resource Center (DRC) in 2017 as a collaborative, pediatric research effort with the goal of understanding the genetic causes of and links between childhood cancer and structural birth defects. The DRC is charged with developing data-driven platforms that integrate large amounts of genomic and clinical data, empowering the collaborative discovery, engagement, and necessary partnerships that are crucial for progress in our biological understanding of diseases, enabling rapid translation to personalized treatments for patients and accelerating discovery of genetic causes and shared biologic pathways within and across these conditions. The DRC is comprised of 3 cores including the Data Resource Portal Core, Data Coordination Core and the Administrative & Outreach Core (AOC). The AOC brings together researchers, physicians, and patient and foundation advocates to support collaborative research and data sharing to accelerate discoveries. The AOC specific aims are to employ outreach strategies including print, web, social media, in-person presentations, conferences, videos, webinars, e-newsletters, surveys, communication strategies, and reports to support accelerated discoveries. The AOC is committed to learning from the childhood cancer and birth defect communities. By capturing, synthesizing, and prioritizing unmet needs for development of the Kids First DRC portal, website, and materials, the AOC engages with researchers, clinicians, foundations, and patient advocates in the childhood cancer and structural birth defect communities. In its first year, the AOC partnered with 32 foundations to launch the Kids First DRC Portal and support data sharing throughout the research community. Key findings during the first six months of requirements gathering revealed the following unmet needs: a) Increase understanding of the disease types, research projects, and the investigators that are a part of the Kids First community b) Highlight the need for cross-disease analyses including structural birth defects and childhood cancers and c) Promote education on the data sharing, agreements, data availability and accessibility. The AOC, gathered pertinent user requirements, conducted educational activities, and engaged prospective users of the researcher community resulting in over 200 users and 22,000 portal views since launch and will continue to use feedback from the research community to further inform the development of the Kids First DRC tools and materials to meet the goals of the program. Citation Format: Tatiana S. Patton, Robert Moulder, Erin Alexander, Donna Vito, Jonathan Waller, Colleen Gaynor, Sarah Thomas, Bailey Farrow, Joseph Yamada, Kim Cullion, Danyelle Winchester, Angela Waanders, Allison Heath, Pichai Raman, Adam Resnick, Jena Lilly. Working together to put kids first: Outreach strategies driving collaborative research, data sharing and cross-disease analysis to accelerate discoveries in pediatric cancer and structural birth defects [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 3356.