ABSTRACT
Background: In 2019, the Open Pediatric Brain Tumor Atlas (OpenPBTA) was created as a global, collaborative open-science initiative to genomically characterize 1,074 pediatric brain tumors and 22 patient-derived cell lines. Here, we extend the OpenPBTA to create the Open Pediatric Cancer (OpenPedCan) Project, a harmonized open-source multi-omic dataset from 6,112 pediatric cancer patients with 7,096 tumor events across more than 100 histologies. Combined with RNA-Seq from the Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA), OpenPedCan contains nearly 48,000 total biospecimens (24,002 tumor and 23,893 normal specimens). Findings: We utilized Gabriella Miller Kids First (GMKF) workflows to harmonize WGS, WXS, RNA-seq, and Targeted Sequencing datasets to include somatic SNVs, InDels, CNVs, SVs, RNA expression, fusions, and splice variants. We integrated summarized CPTAC whole cell proteomics and phospho-proteomics data, miRNA-Seq data, and have developed a methylation array harmonization workflow to include m-values, beta-vales, and copy number calls. OpenPedCan contains reproducible, dockerized workflows in GitHub, CAVATICA, and Amazon Web Services (AWS) to deliver harmonized and processed data from over 60 scalable modules which can be leveraged both locally and on AWS. The processed data are released in a versioned manner and accessible through CAVATICA or AWS S3 download (from GitHub), and queryable through PedcBioPortal and the NCI's pediatric Molecular Targets Platform. Notably, we have expanded PBTA molecular subtyping to include methylation information to align with the WHO 2021 Central Nervous System Tumor classifications, allowing us to create research-grade integrated diagnoses for these tumors. Conclusions: OpenPedCan data and its reproducible analysis module framework are openly available and can be utilized and/or adapted by researchers to accelerate discovery, validation, and clinical translation.
ABSTRACT
Depth separation is a proposed driver of speciation in marine fishes, with marine rockfish (genus Sebastes) providing a potentially informative study system. Sebastes rockfishes are commercially and ecologically important. This genus encompasses more than one hundred species and the ecological and morphological variance between these species provides opportunity for identifying speciation-driving adaptations, particularly along a depth gradient. A reduced-representation sequencing method (ddRADseq) was used to compare 95 individuals encompassing six Sebastes species. In this study, we sought to identify regions of divergence between species that were indicative of divergent adaptation and reproductive barriers leading to speciation. A pairwise comparison of S. chrysomelas (black-and-yellow rockfish) and S. carnatus (gopher rockfish) FST values revealed three major regions of elevated genomic divergence, two of which were also present in the S. miniatus (vermilion rockfish) and S. crocotulus (sunset rockfish) comparison. These corresponded with regions of both elevated DXY values and reduced nucleotide diversity in two cases, suggesting a speciation-with-gene-flow evolutionary model followed by post-speciation selective sweeps within each species. Limited whole-genome resequencing was also performed to identify mutations with predicted effects between S. chrysomelas and S. carnatus. Within these islands, we identified important SNPs in genes involved in immune function and vision. This supports their potential role in speciation, as these are adaptive vectors noted in other organisms. Additionally, changes to genes involved in pigment expression and mate recognition shed light on how S. chrysomelas and S. carnatus may have become reproductively isolated.