FunPredCATH: An ensemble method for predicting protein function using CATH

Motivation

The growth of unannotated proteins in UniProt increases at a very high rate every year due to more efficient sequencing methods. However, the experimental annotation of proteins is a lengthy and expensive process. Using computational techniques to narrow the search can speed up the process by providing highly specific Gene Ontology (GO) terms.

Methodology

We propose an ensemble approach that combines three generic base predictors that predict Gene Ontology (BP, CC and MF) terms from sequences across different species. We train our models on UniProtGOA annotation data and use the CATH domain resources to identify the protein families. We then calculate a score based on the prevalence of individual GO terms in the functional families that is then used as an indicator of confidence when assigning the GO term to an uncharacterised protein.

Methods

In the ensemble, we use a statistics-based method that scores the occurrence of GO terms in a CATH FunFam against a background set of proteins annotated by the same GO term. We also developed a set-based method that uses Set Intersection and Set Union to score the occurrence of GO terms within the same CATH FunFam. Finally, we also use FunFams-Plus, a predictor method developed by the Orengo Group at UCL to predict GO terms for uncharacterised proteins in the CAFA3 challenge.

Evaluation

We evaluated the methods against the CAFA3 benchmark and DomFun. We used the Precision, Recall and F_max metrics and the benchmark datasets that are used in CAFA3 to evaluate our models and compare them to the CAFA3 results. Our results show that FunPredCATH compares well with top CAFA methods in the different ontologies and benchmarks.

Contributions

FunPredCATH compares well with other prediction methods on CAFA3, and the ensemble approach outperforms the base methods. We show that non-IEA models obtain higher F_max scores than the IEA counterparts, while the models including IEA annotations have higher coverage at the expense of a lower F_max score.