OpenPBTA: An Open Pediatric Brain Tumor Atlas

Abstract

Pediatric brain and spinal cancer are the leading disease-related cause of death in children, thus we urgently need curative therapeutic strategies for these tumors. To accelerate such discoveries, the Children's Brain Tumor Network and Pacific Pediatric Neuro-Oncology Consortium created a systematic process for tumor biobanking, model generation, and sequencing with immediate access to harmonized data. We leverage these data to create OpenPBTA, an open collaborative project which establishes over 40 scalable analysis modules to genomically characterize 1,074 pediatric brain tumors. Transcriptomic classification reveals that TP53 loss is a significant marker for poor overall survival in ependymomas and H3 K28-altered diffuse midline gliomas and further identifies universal TP53 dysregulation in mismatch repair-deficient hypermutant high-grade gliomas. OpenPBTA is a foundational analysis platform actively being applied to other pediatric cancers and inform molecular tumor board decision-making, making it an invaluable resource to the pediatric oncology community.

Development of GPC2-directed chimeric antigen receptors using mRNA for pediatric brain tumors

“…RNA sequencing (RNAseq) of pediatric brain tumor samples was completed as described within the Pediatric Brain Tumor Atlas (OpenPBTA; available at https://alexslemonade.github.io/OpenPBTA-manuscript/v/0d99c02483e21557e27957386d419b58fe8cb635/ or from the public CAVATICA project: https://cavatica.sbgenomics.com/u/cavatica/openpbta ). 31 Briefly, 1028 paired-end RNA fastq files, comprising 970 rRNA-depleted and 58 poly-A enriched samples, were aligned to the hg38 human genome using GENCODE V.27 as reference annotation with STAR V.2.6.1d. For comparison with neuroblastoma, data from TARGET ( https://ocg.cancer.gov/programs/target/data-matrix ) were also analyzed.…”

“…com/u/cavatica/openpbta). 31 Briefly, 1028 paired-end RNA fastq files, comprising 970 rRNA-depleted and 58 poly-A enriched samples, were aligned to the hg38 human genome using GENCODE V.27 as reference annotation with STAR V.2.6.1d. For comparison with neuroblastoma, data from TARGET (https://ocg.cancer.gov/programs/ target/ data-matrix) were also analyzed.…”

The Children’s Brain Tumor Network (CBTN) - Accelerating Research in Pediatric Central Nervous System Tumors through Collaboration and Open Science

“…In 2019, Researchers at D3b and Alex's Lemonade Stand Foundation's Childhood Cancer Data Lab launched the Open Pediatric Brain Tumor Atlas (OpenPBTA). OpenPBTA is a first-in-kind, open-science, collaborative analysis and manuscript-writing effort to comprehensively analyze PBTA tumors (6). OpenPBTA openly provides reproducible workflows and processed data on GitHub, PedcBioportal, and CAVATICA supporting multiple research publications as well as informing clinical trial decision-making in molecular tumor boards (7).…”

“…A second dataset of nearly 5,000 samples including tumor/normal WGS and RNA-seq, as well as parental germline WGS, jointly sponsored by GMKF and CCDI (4), along with methylation data for > 1,700 tumors sponsored by NCI's Center for Cancer Research, will be released with no embargo. Additionally, building upon an initial proteogenomic PBTA dataset generated in partnership with the NCI's Clinical Proteomic Tumor Analysis Consortium (CPTAC) ( 5 (6). OpenPBTA openly provides reproducible workflows and processed data on GitHub, PedcBioportal, and CAVATICA supporting multiple research publications as well as informing clinical trial decision-making in molecular tumor boards (7).…”

ALT in Pediatric High-Grade Gliomas Can Occur withoutATRXMutation and is Enriched in Patients with Pathogenic Germline MMR Variants

“…Here, we assess the frequency of ALT, as well as clinical and molecular phenotypes associated with ALT, in a large cohort of pediatric brain tumors from the OpenPBTA, with detailed investigation of HGATs [32][33][34] .…”