The emergence of multi-dimensional genomic data poses new challenges in data analysis. Finding correlated patterns within multiple-sourced biological data is useful in understanding potential interactions between the multi-modal genomic data. Multi-dimensional genomic data contain multiple genomic data types, and different types of genomic data have different scales and units. These data cannot simply be aggregated for analysis. To address this issue, a correlated pattern discovery model incorporating prior knowledge is proposed. Tensor similarity is used to measure the correlation between common patterns. The model is combined with prior knowledge, the expression of which is transformed into constraints. Efficient numerical solutions are designed and analyzed. The proposed method is shown to perform robustly and effectively with both simulated data and real biological data. We conduct experiments on five real cancer datasets to reveal various cancer subtypes. A survival analysis of these subtypes confirms the effectiveness of the model. This method is meaningful for the realization of personalized diagnoses by doctors in the treatment of cancer and other diseases.

Revealing data with intrinsically diagonal block structures is particularly useful for analyzing groups of highly correlated variables. Earlier researches based on non-negative matrix factorization (NMF) have been shown to be effective in representing such data by decomposing the observed data into two factors, where one factor is considered to be the feature and the other the expansion loading from a linear algebra perspective. If the data are sampled from multiple independent subspaces, the loading factor would possess a diagonal structure under an ideal matrix decomposition. However, the standard NMF method and its variants have not been reported to exploit this type of data via direct estimation. To address this issue, a non-negative matrix factorization with multiple constraints model is proposed in this paper. The constraints include an sparsity norm on the feature matrix and a total variational norm on each column of the loading matrix. The proposed model is shown to be capable of efficiently recovering diagonal block structures hidden in observed samples. An efficient numerical algorithm using the alternating direction method of multipliers model is proposed for optimizing the new model. Compared with several benchmark models, the proposed method performs robustly and effectively for simulated and real biological data.

With the exponential growth of biomedical knowledge in unstructured text repositories such as PubMed, it is imminent to establish a knowledge graph-style, efficient searchable and targeted database that can support the need of information retrieval from researchers and clinicians. To mine knowledge from graph databases, most previous methods view a triple in a graph (see Fig. 1) as the basic processing unit and embed the triplet element (i.e. drugs/chemicals, proteins/genes and their interaction) as separated embedding matrices, which cannot capture the semantic correlation among triple elements. To remedy the loss of semantic correlation caused by disjoint embeddings, we propose a novel approach to learn triple embeddings by combining entities and interactions into a unified representation. Furthermore, traditional methods usually learn triple embeddings from scratch, which cannot take advantage of the rich domain knowledge embedded in pre-trained models, and is also another significant reason for the fact that they cannot distinguish the differences implied by the same entity in the multi-interaction triples. In this paper, we propose a novel fine-tuning based approach to learn better triple embeddings by creating weakly supervised signals from pre-trained knowledge graph embeddings. The method automatically samples triples from knowledge graphs and estimates their pairwise similarity from pre-trained embedding models. The triples are then fed pairwise into a Siamese-like neural architecture, where the triple representation is fine-tuned in the manner bootstrapped by triple similarity scores. Finally, we demonstrate that triple embeddings learned with our method can be readily applied to several downstream applications (e.g. triple classification and triple clustering). We evaluated the proposed method on two open-source drug-protein knowledge graphs constructed from PubMed abstracts, as provided by BioCreative. Our method achieves consistent improvement in both triple classification and triple clustering tasks when compared to other state-of-the-art triple embedding methods, with an average 35% improvement of F1 score for the multi-interaction triples.