Motivation: Protein--protein interactions (PPIs) underpin a wide range of biological functions in living organisms. Experimental identification of new PPIs is expensive and time-consuming. The experimental bottleneck has implied an imbalance in terms of data availability: while certain species have been screened exhaustively, other species have not been sufficiently examined. An AI driven protocol for PPI prediction that leverages the massive data accumulated for certain species means a decisive boost for so far understudied species. Results: We present ANIMA (Artificial Neural Interaction Model for Animals), an AI supported cross-species PPI prediction model trained on popular species to predict PPIs in under-researched species. Our experiments demonstrate that our model, when trained on 200 diversely selected animal species, can successfully predict PPIs in other species: ANIMA achieves 95.3% accuracy on other animal species, 91.1% on other eukaryotes, and 82.5% on non-eukaryotes. For a more fine-grained evaluation of the model, we stratify performance rates by the evolutionary distance of test to training sets. We also stratify results by a novel, alignment based score ("representation score") which allows for fine-grained evaluation in terms of its capacity to generalize to unseen interactions. As expected, results demonstrate increasing performance on increasing evolutionary similarity and on increasing identity of interacting proteins, while still showing excellent performance on proteins entirely lacking counterparts in the training set. In comparison with the state of the art, ANIMA demonstrates substantial superiority in terms of performance rates.
Florentino, B. R., Bonidia, R., Carvalho, A., Schoenhuth, A.
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