Supek Group

We perform large-scale bioinformatic studies of multi-omic data from human tumors (somatic mutations, epigenomes and transcriptomes), human populations (germline variation) and metagenomes (incl. human microbiomes). 

We study mechanisms of maintaining genome stability in human cells via statistical analyses of mutation patterns in cancer, which often result from deficient DNA repair.  Next, we are interested in how mRNA synthesis and turnover pathways shape genomes and transcriptomes in health and disease.  Finally, we combine experimental work and genomics to scan cancer genomes for genetic interactions to predict tumor evolution and identify novel synthetic lethalities.  More generally, we study use machine learning approaches to infer gene function from massive genomic data.

• The rules of the nonsense-mediated mRNA decay (NMD) QC pathway were elucidated, and their importance to genetic disease, tumor evolution and immunotherapy was assesed.
  • Read paper “The impact of nonsense-mediated mRNA decay on genetic disease, gene editing and cancer immunotherapy” and review “To NMD or Not To NMD: Nonsense-Mediated mRNA Decay in Cancer and Other Genetic Diseases”
• Mutational signatures of endogenous mutagens APOBEC3A and TLS polymerases were clarified, and mechanisms that promote clustered mutations in cancer revealed.
  • Read paper “Clustered Mutation Signatures Reveal that Error-Prone DNA Repair Targets Mutations to Active Genes” and “DNA mismatch repair promotes APOBEC3-mediated diffuse hypermutation in human cancers”
• By using cell lines as a model, cancer cell vulnerabilities that result as a consequence of some types of disturbed DNA repair and/or mutagenesis were identified.
  • Read papers “Mutational signatures are markers of drug sensitivity of cancer cells” and “Loss of the abasic site sensor HMCES is synthetic lethal with the activity of the APOBEC3A cytosine deaminase in cancer cells”
• Links between local chromatin environment and the cell’s response to DNA damage (incl. during gene editing) and activity of DNA repair were elucidated.
  • Read paper “TP53-dependent toxicity of CRISPR/Cas9 cuts is differential across genomic loci and can confound genetic screening” and preprint “Cell cycle gene alterations associate with a redistribution of mutation risk across chromosomal domains in human cancers”