Extensive complementarity between gene function prediction methods

摘要

Motivation: The number of sequenced genomes rises steadily, but we still lack the knowledge about the biological roles of many genes. Automated function prediction (AFP) is thus a necessity. We hypothesize that AFP approaches which draw on distinct genome features may be useful for predicting different types of gene functions, motivating a systematic analysis of the benefits gained by obtaining and integrating such predictions. Results: Our pipeline amalgamates 5, 133, 543 genes from 2, 071 genomes in a single massive analysis that evaluates five established genomic AFP methodologies. While 1, 227 Gene Ontology terms yielded reliable predictions, the majority of these functions were accessible to only one or two of the methods. Moreover, different methods tend to assign a GO term to non-overlapping sets of genes. Thus, inferences made by diverse AFP methods display a striking complementary, both gene-wise and function-wise. Because of this, a viable integration strategy is to rely on a single most- confident prediction per gene/function, instead of enforcing agreement across multiple AFP methods. Using an information-theoretic approach, we estimate that current databases contain 29.2 bits/gene of known E. coli gene functions. This can be increased by up to 5.5 bits/gene using individual AFP methods, or by 11 additional bits/gene upon integration, thereby providing a highly-ranking predictor on the CAFA2 community benchmark. Availability of more sequenced genomes boosts the predictive accuracy of AFP approaches and also the benefit from integrating them.