Genetic architecture of molecular phenotypes in pediatric brain cancers

It is currently unknown to what extent protein expression is under genetic control in pediatric brain cancers. Here, we aim to identify cis-acting mechanisms that affect protein expression levels and map trans-acting germline variants that perturb proteinprotein interactions within individual brain cancer types and at pancancer level. We will perform protein quantitative trait locus (pQTL) mapping based on rare and common germline variants (SNVs, indels, SVs) from whole genomes and mass spectrometry-based protein quantifications, integrate this data with cis-eQTLs and somatic alterations (eg, missense mutations, CNAs), and infer transcriptional and post-transcriptional mechanisms that affect protein expression levels and proteinprotein interactions. This cis- and trans-pQTL resource will help to better understand the impact of non-coding and protein-coding genetic variation on somatic evolution, drug response, and clinical outcome.