Predictomes: A classifier-curated database of AlphaFold-modeled protein-protein interactions

Predictomes: A classifier-curated database of AlphaFold-modeled protein-protein interactions

April 12, 2024 | Ernst W. Schmid, Johannes C. Walter
The study introduces Predictomes, a comprehensive database of protein-protein interactions (PPIs) curated using AlphaFold-Multimer (AF-M) and a machine learning classifier called SPOC (Structure Prediction and Omics-informed Classifier). AF-M has the potential to identify novel PPIs, but its standard confidence metrics often fail to distinguish true interactions from false positives. To address this, the authors trained SPOC on well-curated datasets, which outperforms existing metrics in separating true from false PPIs, even in proteome-wide screens. They applied SPOC to an all-by-all matrix of 285 human genome maintenance proteins, generating ~40,000 predictions. These predictions are available at predictomes.org, where users can score their own predictions. High-confidence PPIs identified suggest novel hypotheses in genome maintenance. The study provides a framework for interpreting large-scale AF-M screens and lays the foundation for a proteome-wide structural interactome.The study introduces Predictomes, a comprehensive database of protein-protein interactions (PPIs) curated using AlphaFold-Multimer (AF-M) and a machine learning classifier called SPOC (Structure Prediction and Omics-informed Classifier). AF-M has the potential to identify novel PPIs, but its standard confidence metrics often fail to distinguish true interactions from false positives. To address this, the authors trained SPOC on well-curated datasets, which outperforms existing metrics in separating true from false PPIs, even in proteome-wide screens. They applied SPOC to an all-by-all matrix of 285 human genome maintenance proteins, generating ~40,000 predictions. These predictions are available at predictomes.org, where users can score their own predictions. High-confidence PPIs identified suggest novel hypotheses in genome maintenance. The study provides a framework for interpreting large-scale AF-M screens and lays the foundation for a proteome-wide structural interactome.
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[slides and audio] Predictomes%3A A classifier-curated database of AlphaFold-modeled protein-protein interactions