We aim to investigate the role of genetic interactions and their contribution to different pediatric cancers. In particular, we focus on cooperative and mutually exclusive interactions between genes, pathways and processes altered in pediatric cancers as exhibited in cancer genomes of patients. To this end we would like to use whole-genome sequencing data to perform a genetic interaction test. We will first create a binary sample-gene matrix in which we can record for each gene and each sample whether the sample has one or more somatic alterations in that gene. Then, for each pair of genes we count the number of samples that have alterations in both genes (co-occurrence) and the number of samples that have alterations in only one of these genes (mutual exclusivity). By performing permutations, we assess whether the observed counts are significant. We will perform the test per cancer type and over all cancer types. We will further extend this gene level test to the pathway level and might also reanalyze raw sequencing data if needed. In follow-up experiments, frequently occurring or absent combinations will be selected and studied in cellular models for validation and unravelling underlying mechanisms. We are currently performing similar analyses on other pediatric cancer data sets in collaboration with Prof. Stephan Pfister from the Deutsches Krebsforschungszentrum (dkfz, German Cancer Research Center) in Heidelberg, Germany and Dr. Jinghui Zhang from St Jude, Memphis, USA. Analyzing these datasets individually and in combination will provide us with a great opportunity to study genetic interactions in childhood cancer covering a broad set of cancer types. Results will be included in articles and presented at conferences.
We have submitted an abstract entitled “Discovering genetic interactions in the CBTTC dataset” for BioSB2020, a Dutch conference with focus on bioinformatics and systems biology. The abstract was selected for a poster presentation. The conference was originally scheduled for 21-22 April 2020, but (due to restrictions related to Covid- 19) is now postponed to 27-28 October 2020. More information about the meeting can be found at: https://www.aanmelder.nl/biosb2020
PI: Patrick Kemmeren - Princess Máxima Center for Pediatric Oncology
- Dr. Josephine Daub - Princess Máxima Center for Pediatric Oncology
- Dr. Stephan Pfister - DKFZ
- Dr. Jinghui Zhang - St. Jude