Abstract
Thirty to seventy percent of proteins in any given genome have no assigned function and have been labeled as the protein “unknome”. This large knowledge gap prevents the biological community from fully leveraging the plethora of genomic data that is now available. Machine-learning approaches are showing some promise in propagating functional knowledge from experimentally characterized proteins to the correct set of isofunctional orthologs. However, they largely fail to predict enzymatic functions unseen in the training set, as shown by dissecting the predictions made for over 450 enzymes of unknown function from the model bacteria Escherichia coli uxgsing the DeepECTransformer platform. Lessons from these failures can help the community develop machine-learning methods that assist domain experts in making testable functional predictions for more members of the uncharacterized proteome.
Article Summary
Many proteins in any genome, ranging from 30 to 70%, lack an assigned function. This knowledge gap limits the full use of the vast available genomic data. Machine learning has shown promise in transferring functional knowledge from proteins of known functions to similar ones, but largely fails to predict novel functions not seen in its training data. Understanding these failures can guide the development of better machine-learning methods to help experts make accurate functional predictions for uncharacterized proteins.
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