Supplementary data are available at Bioinformatics online.

Distillation is an effective knowledge-transfer technique that uses predicted distributions of a powerful teacher model as soft targets to train a less-parameterized student model. A pre-trained high capacity teacher, however, is not always available. Recently proposed online variants use the aggregated intermediate predictions of multiple student models as targets to train each student model. Although group-derived targets give a good recipe for teacher-free distillation, group members are homogenized quickly with simple aggregation functions, leading to early saturated solutions. In this work, we propose Online Knowledge Distillation with Diverse peers (OKDDip), which performs two-level distillation during training with multiple auxiliary peers and one group leader. In the first-level distillation, each auxiliary peer holds an individual set of aggregation weights generated with an attention-based mechanism to derive its own targets from predictions of other auxiliary peers. Learning from distinct target distributions helps to boost peer diversity for effectiveness of group-based distillation. The second-level distillation is performed to transfer the knowledge in the ensemble of auxiliary peers further to the group leader, i.e., the model used for inference. Experimental results show that the proposed framework consistently gives better performance than state-of-the-art approaches without sacrificing training or inference complexity, demonstrating the effectiveness of the proposed two-level distillation framework.

Background: Identifying disease genes from human genome is an important but challenging task in biomedical research. Machine learning methods can be applied to discover new disease genes based on the known ones. Existing machine learning methods typically use the known disease genes as the positive training set P and the unknown genes as the negative training set N (non-disease gene set does not exist) to build classifiers to identify new disease genes from the unknown genes. However, such kind of classifiers is actually built from a noisy negative set N as there can be unknown disease genes in N itself. As a result, the classifiers do not perform as well as they could be.Result: Instead of treating the unknown genes as negative examples in N, we treat them as an unlabeled set U. We design a novel positive-unlabeled (PU) learning algorithm PUDI (PU learning for disease gene identification) to build a classifier using P and U. We first partition U into four sets, namely, reliable negative set RN, likely positive set LP, likely negative set LN and weak negative set WN. The weighted support vector machines are then used to build a multi-level classifier based on the four training sets and positive training set P to identify disease genes. Our experimental results demonstrate that our proposed PUDI algorithm outperformed the existing methods significantly.Conclusion: The proposed PUDI algorithm is able to identify disease genes more accurately by treating the unknown data more appropriately as unlabeled set U instead of negative set N. Given that many machine learning problems in biomedical research do involve positive and unlabeled data instead of negative data, it is possible that the machine learning methods for these problems can be further improved by adopting PU learning methods, as we have done here for disease gene identification.Availability and implementation: The executable program and data are available at http://www1.i2r.a-star.edu.sg/∼xlli/PUDI/PUDI.html.Contact: xlli@i2r.a-star.edu.sg or yang0293@e.ntu.edu.sgSupplementary information: Supplementary Data are available at Bioinformatics online.

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