• 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

• The rules and impact of nonsense-mediated mRNA decay in human cancers. RGH Lindeboom, F Supek*, B Lehner* (2016) Nature Genetics. (*corr. auth.)

Matched exome and transcriptome data can systematically elucidate the rules of NMD targeting in human tumors, explaining ¾ of the variance in NMD efficiency. Applying our NMD model identifies signatures of positive and negative selection on nonsense mutations in human tumors, and provides a classification for tumor-suppressor genes.

• 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 (2022) bioRxiv

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.