• The impact of nonsense-mediated mRNA decay on genetic disease, gene editing and cancer immunotherapy. RGH Lindeboom, M Vermeulen, B Lehner*, F Supek* (2019) Nature Genetics  

Human genetic diseases differ in whether NMD typically aggravates or alleviates the phenotypic effects of nonsense variants // Failure to trigger NMD is a cause of ineffective gene inactivation by CRISPR–Cas9 gene editing // NMD strongly determines the efficacy of cancer immunotherapy, with only transcripts that escape NMD predicting a response

• Variable efficiency of nonsense-mediated mRNA decay across human tissues, tumors and individuals. G Palou-Marquez, F Supek (2024) bioRxiv 

Matched exome and transcriptome data can systematically elucidate the variation in NMD efficiency between tissues and tumors, by assaying endogenous NMD target transcripts, and also allele-specific expression of nonsense variants in an individual. Nervous system and reproductive tissues have lower NMD efficiency than other tissues. Somatic alteration (e.g. 1q gains) and germline variants change NMD efficiency.

• Matching cell lines with cancer type and subtype of origin via mutational, epigenomic, and transcriptomic patterns. M Salvadores, F Fuster, F Supek (2020) Science Advances.  

A joint analysis of genomes, transcriptomes and epigenomes matches human cancer cell lines to tumor (sub)types in TCGA // ~20% of the 614 examined cell lines were not a good match to the cancer type they were meant to represent // ~7% of cell lines are a close match a different cancer type, sometimes representing instances of metastatic skin cancer

• Prevalence, causes and impact of TP53-loss phenocopying events in human tumors. B Fito, M Salvadores, M Alvarez, F Supek (2023) BMC Biology

Transcriptome analysis suggests that 12% and 8% of tumors and cancer cell lines phenocopy TP53 loss. We identified an additional TP53-loss phenocopying gene, USP28. Deletions in USP28 are associated with a TP53 functional impairment in 2.9-7.6% of breast, bladder, lung, liver and stomach tumors.