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As a fundamental manner for learning and cognition, transfer learning has attracted widespread attention in recent years. Typical transfer learning tasks include unsupervised domain adaptation (UDA) and few-shot learning (FSL), which both attempt to sufficiently transfer discriminative knowledge from the training environment to the test environment to improve the model's generalization performance. Previous transfer learning methods usually ignore the potential conditional distribution shift between environments. This leads to the discriminability degradation in the test environments. Therefore, how to construct a learnable and interpretable metric to measure and then reduce the gap between conditional distributions is very important in the literature. In this article, we design the Conditional Kernel Bures (CKB) metric for characterizing conditional distribution discrepancy, and derive an empirical estimation with convergence guarantee. CKB provides a statistical and interpretable approach, under the optimal transportation framework, to understand the knowledge transfer mechanism. It is essentially an extension of optimal transportation from the marginal distributions to the conditional distributions. CKB can be used as a plug-and-play module and placed onto the loss layer in deep networks, thus, it plays the bottleneck role in representation learning. From this perspective, the new method with network architecture is abbreviated as BuresNet, and it can be used extract conditional invariant features for both UDA and FSL tasks. BuresNet can be trained in an end-to-end manner. Extensive experiment results on several benchmark datasets validate the effectiveness of BuresNet.

Unsupervised domain adaptation is effective in leveraging rich information from a labeled source domain to an unlabeled target domain. Though deep learning and adversarial strategy made a significant breakthrough in the adaptability of features, there are two issues to be further studied. First, hard-assigned pseudo labels on the target domain are arbitrary and error-prone, and direct application of them may destroy the intrinsic data structure. Second, batch-wise training of deep learning limits the characterization of the global structure. In this paper, a Riemannian manifold learning framework is proposed to achieve transferability and discriminability simultaneously. For the first issue, this framework establishes a probabilistic discriminant criterion on the target domain via soft labels. Based on pre-built prototypes, this criterion is extended to a global approximation scheme for the second issue. Manifold metric alignment is adopted to be compatible with the embedding space. The theoretical error bounds of different alignment metrics are derived for constructive guidance. The proposed method can be used to tackle a series of variants of domain adaptation problems, including both vanilla and partial settings. Extensive experiments have been conducted to investigate the method and a comparative study shows the superiority of the discriminative manifold learning framework.

The identification of cancer subtypes is of great importance for understanding the heterogeneity of tumors and providing patients with more accurate diagnoses and treatments. However, it is still a challenge to effectively integrate multiple omics data to establish cancer subtypes. In this paper, we propose an unsupervised integration method, named weighted multi-view low rank representation (WMLRR), to identify cancer subtypes from multiple types of omics data. Given a group of patients described by multiple omics data matrices, we first learn a unified affinity matrix which encodes the similarities among patients by exploring the sparsity-consistent low-rank representations from the joint decompositions of multiple omics data matrices. Unlike existing subtype identification methods that treat each omics data matrix equally, we assign a weight to each omics data matrix and learn these weights automatically through the optimization process. Finally, we apply spectral clustering on the learned affinity matrix to identify cancer subtypes. Experiment results show that the survival times between our identified cancer subtypes are significantly different, and our predicted survivals are more accurate than other state-of-the-art methods. In addition, some clinical analyses of the diseases also demonstrate the effectiveness of our method in identifying molecular subtypes with biological significance and clinical relevance.

Identification of protein complexes is fundamental for understanding the cellular functional organization. With the accumulation of physical protein-protein interaction (PPI) data, computational detection of protein complexes from available PPI networks has drawn a lot of attentions. While most of the existing protein complex detection algorithms focus on analyzing the physical protein-protein interaction network, none of them take into account the "signs"  (i.e., activation-inhibition relationships) of physical interactions. As the "signs"  of interactions reflect the way proteins communicate, considering the "signs"  of interactions can not only increase the accuracy of protein complex identification, but also deepen our understanding of the mechanisms of cell functions. In this study, we proposed a novel Signed Graph regularized Nonnegative Matrix Factorization (SGNMF) model to identify protein complexes from signed PPI networks. In our experiments, we compared the results collected by our model on signed PPI networks with those predicted by the state-of-the-art complex detection techniques on the original unsigned PPI networks. We observed that considering the "signs"  of interactions significantly benefits the detection of protein complexes. Furthermore, based on the predicted complexes, we predicted a set of signed complex-complex interactions for each dataset, which provides a novel insight of the higher level organization of the cell. All the experimental results and codes can be downloaded from http://mail.sysu.edu.cn/home/stsddq@mail.sysu.edu.cn/dai/others/SGNMF.zip.

Interactions between biomolecules play an essential role in various biological processes. For predicting DNA-binding or protein-binding proteins, many machine-learning-based techniques have used various types of features to represent the interface of the complexes, but they only deal with the properties of a single atom in the interface and do not take into account the information of neighborhood atoms directly. This paper proposes a new feature representation method for biomolecular interfaces based on the theory of graph wavelet. The enhanced graph wavelet features (EGWF) provides an effective way to characterize interface feature through adding physicochemical features and exploiting a graph wavelet formulation. Particularly, graph wavelet condenses the information around the center atom, and thus enhances the discrimination of features of biomolecule binding proteins in the feature space. Experiment results show that EGWF performs effectively for predicting DNA-binding and protein-binding proteins in terms of Matthew's correlation coefficient (MCC) score and the area value under the receiver operating characteristic curve (AUC).

With the rapid development of high-throughput experiment techniques for protein-protein interaction (PPI) detection, a large amount of PPI network data are becoming available. However, the data produced by these techniques have high levels of spurious and missing interactions. This study assigns a new reliably indication for each protein pairs via the new generative network model (RIGNM) where the scale-free property of the PPI network is considered to reliably identify both spurious and missing interactions in the observed high-throughput PPI network. The experimental results show that the RIGNM is more effective and interpretable than the compared methods, which demonstrate that this approach has the potential to better describe the PPI networks and drive new discoveries.

Biomarker identification and cancer classification are two closely related problems. In gene expression data sets, the correlation between genes can be high when they share the same biological pathway. Moreover, the gene expression data sets may contain outliers due to either chemical or electrical reasons. A good gene selection method should take group effects into account and be robust to outliers. In this paper, we propose a Laplace naive Bayes model with mean shrinkage (LNB-MS). The Laplace distribution instead of the normal distribution is used as the conditional distribution of the samples for the reasons that it is less sensitive to outliers and has been applied in many fields. The key technique is the L1 penalty imposed on the mean of each class to achieve automatic feature selection. The objective function of the proposed model is a piecewise linear function with respect to the mean of each class, of which the optimal value can be evaluated at the breakpoints simply. An efficient algorithm is designed to estimate the parameters in the model. A new strategy that uses the number of selected features to control the regularization parameter is introduced. Experimental results on simulated data sets and 17 publicly available cancer data sets attest to the accuracy, sparsity, efficiency, and robustness of the proposed algorithm. Many biomarkers identified with our method have been verified in biochemical or biomedical research. The analysis of biological and functional correlation of the genes based on Gene Ontology (GO) terms shows that the proposed method guarantees the selection of highly correlated genes simultaneously

The functional annotation of proteins is one of the most important tasks in the post-genomic era. Although many computational approaches have been developed in recent years to predict protein function, most of these traditional algorithms do not take interrelationships among functional terms into account, such as different GO terms usually coannotate with some common proteins. In this study, we propose a new functional similarity measure in the form of Jaccard coefficient to quantify these interrelationships and also develop a framework for incorporating GO term similarity into protein function prediction process. The experimental results of cross-validation on S. cerevisiae and Homo sapiens data sets demonstrate that our method is able to improve the performance of protein function prediction. In addition, we find that small size terms associated with a few of proteins obtain more benefit than the large size ones when considering functional interrelationships. We also compare our similarity measure with other two widely used measures, and results indicate that when incorporated into function prediction algorithms, our proposed measure is more effective. Experiment results also illustrate that our algorithms outperform two previous competing algorithms, which also take functional interrelationships into account, in prediction accuracy. Finally, we show that our method is robust to annotations in the database which are not complete at present. These results give new insights about the importance of functional interrelationships in protein function prediction.

Detecting protein complexes from protein interaction networks is one major task in the postgenome era. Previous developed computational algorithms identifying complexes mainly focus on graph partition or dense region finding. Most of these traditional algorithms cannot discover overlapping complexes which really exist in the protein-protein interaction (PPI) networks. Even if some density-based methods have been developed to identify overlapping complexes, they are not able to discover complexes that include peripheral proteins. In this study, motivated by recent successful application of generative network model to describe the generation process of PPI networks and to detect communities from social networks, we develop a regularized sparse generative network model (RSGNM), by adding another process that generates propensities using exponential distribution and incorporating Laplacian regularizer into an existing generative network model, for protein complexes identification. By assuming that the propensities are generated using exponential distribution, the estimators of propensities will be sparse, which not only has good biological interpretation but also helps to control the overlapping rate among detected complexes. And the Laplacian regularizer will lead to the estimators of propensities more smooth on interaction networks. Experimental results on three yeast PPI networks show that RSGNM outperforms six previous competing algorithms in terms of the quality of detected complexes. In addition, RSGNM is able to detect overlapping complexes and complexes including peripheral proteins simultaneously. These results give new insights about the importance of generative network models in protein complexes identification.