Some researchers [3,11,39] suggested that protein function prediction should be addressed as an unbalanced classification algorithm. Additional experiments were conducted to investigate the benefit of using Y˜ (weighted) in place of Y (unweighted). Y˜ differentially weights the labels, and puts more emphasis on the labels that have fewer member proteins. In contrast, Y equally weights all the labels. The definition of Y and Y˜ are provided in the section of Method. We report the results of MNet using Y˜ (weighted) and Y (unweighted) in Table 2 of the Additional File 1.