Protein function prediction is to assign biological or biochemical functions to proteins, and it is a challenging computational problem characterized by several factors: (1) the number of function labels (annotations) is large; (2) a protein may be associated with multiple labels; (3) the function labels are structured in a hierarchy; and (4) the labels are incomplete. Current predictive models often assume that the labels of the labeled proteins are complete, i.e. no label is missing. But in real scenarios, we may be aware of only some hierarchical labels of a protein, and we may not know whether additional ones are actually present. The scenario of incomplete hierarchical labels, a challenging and practical problem, is seldom studied in protein function prediction. In this paper, we propose an algorithm to Predict protein functions using Incomplete hierarchical LabeLs (PILL in short). PILL takes into account the hierarchical and the flat taxonomy similarity between function labels, and defines a Combined Similarity (ComSim) to measure the correlation between labels. PILL estimates the missing labels for a protein based on ComSim and the known labels of the protein, and uses a regularization to exploit the interactions between proteins for function prediction. PILL is shown to outperform other related techniques in replenishing the missing labels and in predicting the functions of completely unlabeled proteins on publicly available PPI datasets annotated with MIPS Functional Catalogue and Gene Ontology labels. The empirical study shows that it is important to consider the incomplete annotation for protein function prediction. The proposed method (PILL) can serve as a valuable tool for protein function prediction using incomplete labels. The Matlab code of PILL is available upon request.

Long non-coding RNAs (lncRNAs) play crucial roles in complex disease diagnosis, prognosis, prevention, and treatment, but only a small portion of lncRNA-disease associations have been experimentally verified. Various computational models have been proposed to identify lncRNA-disease associations by integrating heterogeneous data sources. However, existing models generally ignore the intrinsic structure of data sources or treat them as equally relevant, while they may not be. To accurately identify lncRNA-disease associations, we propose a Matrix Factorization based LncRNA-Disease Association prediction model (MFLDA in short). MFLDA decomposes data matrices of heterogeneous data sources into low-rank matrices via matrix tri-factorization to explore and exploit their intrinsic and shared structure. MFLDA can select and integrate the data sources by assigning different weights to them. An iterative solution is further introduced to simultaneously optimize the weights and low-rank matrices. Next, MFLDA uses the optimized low-rank matrices to reconstruct the lncRNA-disease association matrix and thus to identify potential associations. In five-fold cross validation experiments to identify verified lncRNA-disease associations, MFLDA achieves an Area Under the receiver operating characteristic Curve (AUC) of 0.7408, at least 3% higher than those given by state-of-the-art data fusion based computational models. An empirical study on identifying masked lncRNA-disease associations again shows that MFLDA can identify potential associations more accurately than competing models. A case study on identifying lncRNAs associated with breast, lung, and stomach cancers show that 38 out of 45 (84%) associations predicted by MFLDA are supported by recent biomedical literature and further proves the capability of MFLDA in identifying novel lncRNA-disease associations. MFLDA is a general data fusion framework, and as such it can be adopted to predict associations between other biological entities. The source code for MFLDA is available at: http://mlda.swu.edu.cn/codes.php?name=MFLDA. gxyu@swu.edu.cn Supplementary data are available at Bioinformatics online.

Annotating the functional properties of gene products, i.e., RNAs and proteins, is a fundamental task in biology. The Gene Ontology database (GO) was developed to systematically describe the functional properties of gene products across species, and to facilitate the computational prediction of gene function. As GO is routinely updated, it serves as the gold standard and main knowledge source in functional genomics. Many gene function prediction methods making use of GO have been proposed. But no literature review has summarized these methods and the possibilities for future efforts from the perspective of GO. To bridge this gap, we review the existing methods with an emphasis on recent solutions. First, we introduce the conventions of GO and the widely adopted evaluation metrics for gene function prediction. Next, we summarize current methods of gene function prediction that apply GO in different ways, such as using hierarchical or flat inter-relationships between GO terms, compressing massive GO terms and quantifying semantic similarities. Although many efforts have improved performance by harnessing GO, we conclude that there remain many largely overlooked but important topics for future research.

In multiview multilabel learning, each object is represented by several heterogeneous feature representations and is also annotated with a set of discrete nonexclusive labels. Previous studies typically focus on capturing the shared latent patterns among multiple views, while not sufficiently considering the diverse characteristics of individual views, which can cause performance degradation. In this article, we propose a novel approach [individuality- and commonality-based multiview multilabel learning (ICM2L)] to explicitly explore the individuality and commonality information of multilabel multiple view data in a unified model. Specifically, a common subspace is learned across different views to capture the shared patterns. Then, multiple individual classifiers are exploited to explore the characteristics of individual views. Next, an ensemble strategy is adopted to make a prediction. Finally, we develop an alternative solution to joinly optimize our model, which can enhance the robustness of the proposed model toward rare labels and reinforce the reciprocal effects of individuality and commonality among heterogeneous views, and thus further improve the performance. Experiments on various real-word datasets validate the effectiveness of ICM2L against the state-of-the-art solutions, and ICM2L can leverage the individuality and commonality information to achieve an improved performance as well as to enhance the robustness toward rare labels.

BRWLDA: bi-random walks for predicting lncRNA-disease associations BRWLDA: bi-random walks for predicting lncRNA-disease associations