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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.

Brain tumors are the leading cause of disease-related death in children and young adults ages 0-19 in largely populated countries such as the United States. In one year alone, 4,000 children and young adults will be diagnosed with a brain or central nervous system tumor in the United States. Brain tumors are complex and difficult to treat in growing children, with current treatments oftentimes causing significant and lifelong side effects. Furthermore, there have only been five drugs in the last 20 years approved by the FDA to treat pediatric brain tumors. Founded in 2011, the Children’s Brain Tumor Network (CBTN) is focused on accelerating the pace of translational research, the discovery of new treatments, and informing precision medicine for children diagnosed with brain tumors. CBTN comprises 32 member institutions/hospitals having over 4700 patient subjects enrolled, spanning 30+ brain tumor diagnoses, over 66,000 biobanked samples and 150 preclinical models. Longitudinal clinical data is also collected for every subject that is enrolled in the observational protocol. Through large scale data generation efforts funded by the NCI and foundational support, CBTN has whole genome, RNA-seq and other molecular characterization for over half of the enrolled patient population. Additionally, efforts have been underway to collect all pathology and radiology imaging and reporting for the subjects. With sequencing being done by multiple vendors, imaging protocols being different across multiple hospitals, and complex clinical treatment and longitudinal follow up data being translated from EHR systems, CBTN has created a rich, but complex, data landscape that is the largest of its kind in the world. In order to accelerate the process of going from data to cures, the data needs to be centralized, organized, and easily distributable. To do this, CBTN has built a first of its kind data workflow that acts as the inventory system for its various data assets. Using a modern data stack including dbt, PostgresSQL, Meltano and AWS, combined with utilization of FHIR as an interchange standard, data from multiple disparate sources such as REDcap, EHR systems, and PAC systems flow in near “real-time” to be utilized as integrated data resources The result of this modern, multimodal, and multi-institutional warehouse allows CBTN to distribute data quickly and accurately to translational researchers around the world and contribute data to key research efforts such as AACR Project Genie, Kids First Data Resource Center, NCI Childhood Cancer Data Initiative, and the NCI’s Open Targets Platform. Citation Format: Bailey K. Farrow, Nicholas Van Kuren, Nathan Young, Christopher Friedman, Meen Chul Kim, Alex Lubneuski, Jennifer Mason, Thinh (Bin) Nguyen, Zeinab Helili, Elizabeth Frenkel, Catherine Sullivan, Ariana Familiar, Yuankun Zhu, Mateusz Koptyra, Tatiana Patton, Jena Lilly, Phillip B. Storm, Adam Resnick, Allison P. Heath. Establishing a multimodal data warehousing platform to accelerate discoveries in pediatric brain tumors for the Children’s Brain Tumor Network. [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 3565.