For example, the top ranked protein PLCG1 in forward ranking (File S1) is known to be involved in 19 KEGG pathways (http://www.genome.jp/dbget-bin/www_bget?hsa:5335) while the top ranked protein CBL in reverse ranking (File S2) is also involved in 9 pathways, including the regulation of the vascular malformation/cancer pathway of PI3K (PIK3CA) –PTEN – PKB/AKT – mTOR (http://www.genome.jp/dbget-bin/www_bget?hsa:867). The gene discussed is AKT1; the disease is cancer.