Computational design and evaluation of optimal bait sets for scalable proximity proteomics

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Udgivet i:Nature Communications vol. 16, no. 1 (2025), p. 9333-9350
Hovedforfatter: Kasmaeifar, Vesal
Andre forfattere: Sedighi, Saya, Gingras, Anne-Claude, Campbell, Kieran R.
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Nature Publishing Group
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024 7 |a 10.1038/s41467-025-64383-1  |2 doi 
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100 1 |a Kasmaeifar, Vesal  |u Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Sinai Health, Toronto, ON, Canada (ROR: https://ror.org/044790d95) (GRID: grid.492573.e) (ISNI: 0000 0004 6477 6457); Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada (ROR: https://ror.org/03dbr7087) (GRID: grid.17063.33) (ISNI: 0000 0001 2157 2938) 
245 1 |a Computational design and evaluation of optimal bait sets for scalable proximity proteomics 
260 |b Nature Publishing Group  |c 2025 
513 |a Journal Article 
520 3 |a The spatial organization of proteins within eukaryotic cells underlies essential biological processes and can be mapped by identifying nearby proteins using proximity-dependent biotinylation approaches such as BioID. When applied systematically to hundreds of bait proteins, BioID has localized thousands of endogenous proteins in human cells, generating a comprehensive view of subcellular organization. However, the need for large bait sets limits the scalability of BioID for context-dependent spatial profiling across different cell types, states, or perturbations. To address this, we develop a benchmarking framework with multiple complementary metrics to assess how well a given bait subset recapitulates the structure and coverage of a reference BioID dataset. We also introduce GENBAIT, a genetic algorithm-based method that identifies optimized bait subsets predicted to retain maximal spatial information while reducing the total number of baits. Applied to three large BioID datasets, GENBAIT consistently selected subsets representing less than one-third of the original baits while preserving high coverage and network integrity. This flexible, data-driven approach enables intelligent bait selection for targeted, context-specific studies, thereby expanding the accessibility of large-scale subcellular proteome mapping.Proximity-dependent biotinylation maps protein locations using multiple bait proteins, limiting scalability. Here, the authors present GENBAIT, a computational tool that selects optimal baits to reduce the number of experiments required while preserving subcellular organization. 
653 |a Datasets 
653 |a Proteomics 
653 |a Mutation 
653 |a Labeling 
653 |a Baits 
653 |a Feature selection 
653 |a Proximity 
653 |a Data analysis 
653 |a Computer applications 
653 |a Maps 
653 |a Biological activity 
653 |a Localization 
653 |a Proteins 
653 |a Machine learning 
653 |a Peptide mapping 
653 |a Spatial data 
653 |a Genetic algorithms 
653 |a Proteomes 
653 |a Biotinylation 
653 |a Enzymes 
653 |a Software 
653 |a Environmental 
700 1 |a Sedighi, Saya  |u Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Sinai Health, Toronto, ON, Canada (ROR: https://ror.org/044790d95) (GRID: grid.492573.e) (ISNI: 0000 0004 6477 6457); Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada (ROR: https://ror.org/03dbr7087) (GRID: grid.17063.33) (ISNI: 0000 0001 2157 2938) 
700 1 |a Gingras, Anne-Claude  |u Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Sinai Health, Toronto, ON, Canada (ROR: https://ror.org/044790d95) (GRID: grid.492573.e) (ISNI: 0000 0004 6477 6457); Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada (ROR: https://ror.org/03dbr7087) (GRID: grid.17063.33) (ISNI: 0000 0001 2157 2938) 
700 1 |a Campbell, Kieran R.  |u Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Sinai Health, Toronto, ON, Canada (ROR: https://ror.org/044790d95) (GRID: grid.492573.e) (ISNI: 0000 0004 6477 6457); Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada (ROR: https://ror.org/03dbr7087) (GRID: grid.17063.33) (ISNI: 0000 0001 2157 2938); Department of Statistical Sciences, University of Toronto, Toronto, ON, Canada (ROR: https://ror.org/03dbr7087) (GRID: grid.17063.33) (ISNI: 0000 0001 2157 2938); Department of Computer Science, University of Toronto, Toronto, ON, Canada (ROR: https://ror.org/03dbr7087) (GRID: grid.17063.33) (ISNI: 0000 0001 2157 2938); Ontario Institute of Cancer Research, Toronto, ON, Canada (ROR: https://ror.org/043q8yx54) (GRID: grid.419890.d) (ISNI: 0000 0004 0626 690X); Vector Institute, Toronto, ON, Canada (ROR: https://ror.org/03kqdja62) (GRID: grid.494618.6) (ISNI: 0000 0005 0272 1351) 
773 0 |t Nature Communications  |g vol. 16, no. 1 (2025), p. 9333-9350 
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