The Toth-Petroczy group comprises an interdisciplinary team of computational biologists, computer scientists, molecular biologists, biochemists and biophysicists. The group aims to understand protein sequence space in the light of evolution and erroneous protein production with focus on intrinsically disordered proteins regions (IDRs).

The two main research directions in the lab include:

1) Sequence-to-function paradigm of intrinsically disordered regions and condensate forming proteins.

2) Phenotypic mutations in evolution and diseases¹.

The group uses an interdisciplinary approach by developing novel mechanistic^2,3 and machine learning/deep learning algorithms focusing on evolutionary and/or structural information⁴, and performing experimental validation and high-throughput screenings⁵. Specifically, the group has designed an alignment-free algorithm to assess homology between unalignable IDR sequences (SHARK-dive)⁶ and developed a method to identify conserved motifs within a set of homologous IDR sequences (SHARK-capture). The group has developed the CrowDsourcing Condensate Database and Encyclopedia (CD-CODE.org)⁷, that catalogues known condensates and their constituent proteins, and trained a predictor of proteins involved in condensates (PICNIC.cd-code.org) across organisms⁸.

References:

1. Romero Romero ML, Landerer C, Poehls J, Toth-Petroczy A. Phenotypic mutations contribute to protein diversity and shape protein evolution. Protein Sci Publ Protein Soc. 2022;31(9):e4397. https://doi.org/10.1002/pro.4397
2. Landerer C, Poehls J, Toth-Petroczy A. Fitness Effects of Phenotypic Mutations at Proteome-Scale Reveal Optimality of Translation Machinery. Mol Biol Evol. 2024;41(3):msae048. https://doi.org/10.1093/molbev/msae048
3. Landerer C, Scheremetjew M, Moon H, Hersemann L, Toth-Petroczy A. deTELpy: Python package for high-throughput detection of amino acid substitutions in mass spectrometry datasets. Bioinforma Oxf Engl. 2024;40(7):btae424. https://doi.org/10.1093/bioinformatics/btae424
4. Luppino F, Adzhubei IA, Cassa CA, Toth-Petroczy A. DeMAG predicts the effects of variants in clinically actionable genes by integrating structural and evolutionary epistatic features. Nat Commun. 2022;14(1). https://doi.org/10.1038/s41467-023-37661-z
5. Romero Romero ML, Poehls J, Kirilenko A, Richter D, Jumel T, Shevchenko A, Toth-Petroczy A. Environment modulates protein heterogeneity through transcriptional and translational stop codon readthrough. Nat Commun. 2024;15(1):4446. https://doi.org/10.1038/s41467-024-48387-x
6. Chow CFW, Ghosh S, Hadarovich A, Toth-Petroczy A. SHARK enables sensitive detection of evolutionary homologs and functional analogs in unalignable and disordered sequences. Proc Natl Acad Sci. 2024;121(42):e2401622121. https://doi.org/10.1073/pnas.2401622121
7. Rostam N, Ghosh S, Chow CFW, Hadarovich A, Landerer C, Ghosh R, Moon H, Hersemann L, Mitrea DM, Klein IA, Hyman AA, Toth-Petroczy A. CD-CODE: crowdsourcing condensate database and encyclopedia. Nat Methods. 2023;20(5):673-676. https://doi.org/10.1038/s41592-023-01831-0
8. Hadarovich A, Singh HR, Ghosh S, Rostam N, Hyman AA, Toth-Petroczy A. PICNIC accurately predicts condensate-forming proteins regardless of their structural disorder across organisms. Published online June 5, 2023. https://doi.org/10.1101/2023.06.01.543229