Heuristic network search algorithm based on the Ontology Fingerprint. A) The gene-gene similarity scores among the 40 genes of interest were converted into probabilities of adding or deleting edges respectively: i) the similarity scores were ranked in ascending order, and each pair of genes was assigned a corresponding rank R (column "Rank ascendingly"); the probability of adding an edge was obtained by the percentage of its ascending rank out of the total ascending ranks (formula on the left of the arrow); ii) similarly, the probability of deleting an edge was assigned by the percentage of the gene pair's descending rank (column "Rank decendingly") out of the total descending ranks (formula on the right of the arrow). These probabilities ensure that the higher the similarity score of a gene pair, the greater possibility of adding the edge between the two genes; and the lower the similarity score of a gene pair, the more likely the edge between the two genes will be deleted. B) Heuristic rules of adding or deleting edges from the canonical network. A network was updated by either deleting or adding an edge sequentially: i) for deleting edges, an edge was sampled according to its deletion probability (p'); the sampled edge has to exist in the current network and the edges from signals to their corresponding receptors were not allowed to be deleted; ii) for adding edges, an edge was sampled according to its addition probability (p); the sampled edge should not appear in the current network, and the edges between signals, between receptors, between signal and non-receptor, and from other nodes to signal are not allowed to be added.