Figure 1

A domain-centric GO approach to automatically infer GO annotations for individual domains and supra-domains. The flowchart in the left panel illustrates three major steps of the proposed approach, including (Step 1) the preparation of the correspondence matrix between domains/supra-domains and GO terms from protein-level annotations in UniProtKB-GOA and domain architectures in SUPERFAMILY database, (Step 2) two types of statistical inference followed by FDR calculation, and (Step 3) following the true-path rule to obtain the complete domain-centric GO annotations. The overall inference (I), relative inference (II) and the significance measure (III) are illustrated in the middle panel, both mathematically and graphically. Further illustration (IV) is given by specifying an example of inferring associations between a supra-domain (i.e., '82199,57667') and a GO term (i.e., 'stem cell maintenance') in the right panel. Notably, there are a total of three direct parental GO terms (i.e., 'developmental process', 'negative regulation of cell differentiation', and 'stem cell development') for 'stem cell maintenance', and N _pa is the total number of Uniprots that can be annotated by any direct parental GO terms.