• Copy number losses of oncogenes and gains of tumor suppressor genes generate common driver mutations. E Besedina, F Supek (2024) Nature Communications.  

Oncogenes may simultaneously exhibit signatures of positive selection and also negative selection in different gene segments. | We reveal a general trend of increased positive selection on oncogene mutations not only upon CNA gains but also upon CNA deletions. | Similarly, we observe a surprising positive interaction between mutations and CNA gains in tumor suppressor genes. 

• DiffInvex identifies evolutionary shifts in driver gene repertoires during tumorigenesis and chemotherapy. A Khalil, F Supek (2025) Nature Communications.  

In >11,000 somatic whole-genome sequences from ~30 tissues,  DiffInvex identifies genes where point mutations are under conditional selection during exposure to specific chemotherapeutics. | Cancer gains drug resistance via point mutations rarely, and when it does this is achieved by gaining additional mutations in standard driver genes: PIK3CA, APC, MAP2K4, MAP3K1, SMAD4  and STK11. | Normal-cell positive selection observed in ARID1A and confirmed in NOTCH1 gene.

• Passenger mutations accurately classify human tumors. M Salvadores, D Mas-Ponte, F Supek (2019) PLOS Comp Biol.  

Density of somatic mutations across chromosomal domains is a mutational phenotype that can differentiate human tissues // Driver mutations are poor classifiers of cancer (sub)type, while passenger mutation-based phenotypes are highly predictive // Trinucleotide signatures and regional mutation density phenotypes are complementary in classifying tumors.

• Whole genome DNA sequencing provides an atlas of somatic mutagenesis in healthy human cells and identifies a tumor-prone cell type. I Franco, H Helgadottir, … D Mas-Ponte, …., F Supek & M Eriksson (2019) Genome Biology.

Multiple cell types from diverse healthy somatic tissues usually display a stereotyped mutation profile. However, the same tissue can sometimes harbor cells with distinct mutation profiles associated to different differentiation states. For example, we identify a cell type in the kidney with unusual mutation rate increase in active chromatin.