Translating Pediatric Cancer Proteogenomic Data into Biological and Clinical Insights

Project Summary This project aims to harness proteogenomic data to advance biological understanding and therapeutic opportunities for pediatric cancers. Building on our leadership in the Clinical Proteomic Tumor Analysis Consortium (CPTAC), where we co-led over half of the flagship studies, we will apply our established analytical frameworks and specialized tools to multi-omics data from the Kids First Pediatric Research Program and Childhood Cancer Data Initiative (CCDI). Our initial focus includes brain tumors and leukemias such as medulloblastoma, ependymoma, high-grade glioma, ATRT, AML, and T-ALL. Available data span whole exome sequencing, RNA-seq, proteomics, phosphoproteomics, acetylomics, ubiquitylomics, glycoproteomics, and metabolomics. We will lead integrative analyses across four key areas: 1) Neoantigen Discovery: Using our NeoFlow2 pipeline and PepQueryMHC algorithm, we will identify and prioritize tumor-specific and non-canonical antigens for immunotherapy development. 2) Protein Isoform Analysis: Applying SEPepQuant, we will resolve isoform-level expression and regulation, integrating proteomics and transcriptomics to reveal novel biological features relevant to pediatric tumorigenesis. 3) PTM Analysis: Leveraging our suite of tools—including LinkedOmics, IDPpub, and CoPheeMap—we will investigate signaling dynamics, subtype-specific pathways, and actionable PTM events. 4) Pathway and Network Analysis: We will deploy WebGestalt, FunMap, and LinkedOmics to interpret multi-omics data, uncover dysregulated networks, and generate mechanistic hypotheses with therapeutic potential. Our workflows are scalable, modular, and cloud-enabled, ensuring rapid deployment and interoperability with other PGDAC pipelines. We will collaborate closely with PGDAC partners, data generators, and disease experts to maximize impact, deliver biologically grounded insights, and support precision oncology for children with cancer.