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bioRxiv · 10.1101/275487

Towards region-specific propagation of protein functions

Koo, D. C. E.·Bonneau, R.
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Abstract

MotivationDue to the nature of experimental annotation, most protein function prediction methods operate at the protein-level, where functions are assigned to full-length proteins based on overall similarities. However, most proteins function by interacting with other proteins or molecules, and many functional associations should be limited to specific regions rather than the entire protein length. Most domain-centric function prediction methods depend on accurate domain family assignments to infer relationships between domains and functions, with regions that are unassigned to a known domain-family left out of functional evaluation. Given the abundance of residue-level annotations currently available, we present a function prediction methodology that automatically infers function labels of specific protein regions using protein-level annotations and multiple types of region-specific features.\n\nResultsWe apply this method to local features obtained from InterPro, UniProtKB and amino acid sequences and show that this method improves both the accuracy and region-specificity of protein function transfer and prediction by testing on both human and yeast proteomes. We compare region-level predictive performance of our method against that of a whole-protein baseline method using a held-out dataset of proteins with structurally-verified binding sites and also compare protein-level temporal holdout predictive performances to expand the variety and specificity of GO terms we could evaluate. Our results can also serve as a starting point to categorize GO terms into site-specific and whole-protein terms and select prediction methods for different classes of GO terms.\n\nAvailabilityThe code is freely available at: https://github.com/ek1203/region_spec_func_pred

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Koo, D. C. E., Bonneau, R.. 2018-03-02. Towards region-specific propagation of protein functions. https://doi.org/10.1101/275487

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