Extended Data Fig. 1: Overview of process for creating the set of human gene functions.

First, experimental results from the scientific literature are captured as primary GO annotations, and stored in the GO knowledgebase (GO KB). The next step is phylogenetic integration: a massive corpus of primary annotations for genes in multiple different organisms was integrated using phylogenetic trees that represent the evolutionary relationships between genes. For each gene family tree, selected primary annotations are used to construct an explicit evolutionary model of gains and losses of gene function along branches of the phylogenetic tree, and the evolutionary model is then used to create the integrated PAN-GO annotations for human genes. The set of human gene functions reported here comprises nearly 69,000 integrated annotations.