Fig. 3

Feature generation for directions and signs. a ‘chromatin silencing’ negatively regulates ‘transcription, DNA-templated’. Thus, ‘chromatin silencing’ is negative regulator whereas ‘transcription, DNA-templated’ is a regulatee. If protein p1 and p2 is annotated to ‘chromatin silencing’ and ‘transcription, DNA-templated’ respectively, the two GO terms compose a p1 → p2 negative regulation pair, which represents direction and sign between two GO terms. b Feature generation procedures are explained with a toy example related to Wnt signaling pathway. There are four regulators (GO:0030177, GO:0030111, GO:0090263, GO:0090090), among which two are positive regulators (GO:0030177, GO:0090263) and one is a negative regulator (GO:0090090). Protein p1 is annotated to four GO terms (GO:0016055, GO:0030177, GO:0030111, GO:0090263), whereas protein p2 is annotated to three GO terms (GO:0030111, GO:0060070, GO:0090090). Protein p2 is not directly annotated to ‘Wnt signaling pathway’, but to ‘canonical Wnt signaling pathway’. Nonetheless, since ‘canonical Wnt signaling pathway’ is a ‘Wnt signaling pathway’, protein p2 is related to ‘Wnt signaling pathway’. c For GO1 and GO2 to which protein p1 and p2 are annotated respectively, we determined whether GO1 (positively/negatively) regulates GO2. If it did, GO1 and GO2 became a p1 → p2 (positive/negative) regulation pair. If it did not, we determined whether GO1 (positively/negatively) regulates any ancestors of GO2. Then, GO1 and the most specific ancestor of GO2 became a p1 → p2 (positive/negative) regulation pair. That way, we found (positive/negative) regulation pairs for p1 → p2, and p2 → p1 direction. To represent PPIs, we used regulation pairs as features. For directions, directions of regulation pairs were encoded as feature values. p1 → p2 (positive/negative) regulation pairs had the value of one, whereas p2 → p1 (positive/negative) regulation pairs had − 1. d For signs, signs of regulation pairs were encoded as feature values. p1 → p2 positive regulation pairs had the value of one, whereas p1 → p2 negative regulation pairs had − 1. Abbreviations: GO, gene ontology; WSP: Wnt signaling pathway