Integrative methods for analyzing big data in precision medicine

We provide an overview of recent developments in big data analyses in the context of precision medicine and health informatics. With the advance in technologies capturing molecular and medical data, we entered the area of “Big Data” in biology and medicine. These data offer many opportunities to advance precision medicine. We outline key challenges in precision medicine and present recent advances in data integration-based methods to uncover personalized information from big data produced by various omics studies. We survey recent integrative methods for disease subtyping, biomarkers discovery, and drug repurposing, and list the tools that are available to domain scientists. Given the ever-growing nature of these big data, we highlight key issues that big data integration methods will face

A representation learning model based on variational inference and graph autoencoder for predicting lncRNA‑disease associations

Background: Numerous studies have demonstrated that long non-coding RNAs are related to plenty of human diseases. Therefore, it is crucial to predict potential lncRNAdisease associations for disease prognosis, diagnosis and therapy. Dozens of machine learning and deep learning algorithms have been adopted to this problem, yet it is still challenging to learn efficient low-dimensional representations from high-dimensional features of lncRNAs and diseases to predict unknown lncRNA-disease associations accurately. Results: We proposed an end-to-end model, VGAELDA, which integrates variational inference and graph autoencoders for lncRNA-disease associations prediction. VGAELDA contains two kinds of graph autoencoders. Variational graph autoencoders (VGAE) infer representations from features of lncRNAs and diseases respectively, while graph autoencoders propagate labels via known lncRNA-disease associations. These two kinds of autoencoders are trained alternately by adopting variational expectation maximization algorithm. The integration of both the VGAE for graph representation learning, and the alternate training via variational inference, strengthens the capability of VGAELDA to capture efficient low-dimensional representations from high-dimensional features, and hence promotes the robustness and preciseness for predicting unknown lncRNA-disease associations. Further analysis illuminates that the designed co-training framework of lncRNA and disease for VGAELDA solves a geometric matrix completion problem for capturing efficient low-dimensional representations via a deep learning approach. Conclusion: Cross validations and numerical experiments illustrate that VGAELDA outperforms the current state-of-the-art methods in lncRNA-disease association prediction. Case studies indicate that VGAELDA is capable of detecting potential lncRNAdisease associations. The source code and data are available at https:// github. com/ zhang labNKU/ VGAEL DA

A message passing framework with multiple data integration for miRNA-disease association prediction

Micro RNA or miRNA is a highly conserved class of non-coding RNA that plays an important role in many diseases. Identifying miRNA-disease associations can pave the way for better clinical diagnosis and finding potential drug targets. We propose a biologically-motivated data-driven approach for the miRNA-disease association prediction, which overcomes the data scarcity problem by exploiting information from multiple data sources. The key idea is to enrich the existing miRNA/disease-protein-coding gene (PCG) associations via a message passing framework, followed by the use of disease ontology information for further feature filtering. The enriched and filtered PCG associations are then used to construct the inter-connected miRNA-PCG-disease network to train a structural deep network embedding (SDNE) model. Finally, the pre-trained embeddings and the biologically relevant features from the miRNA family and disease semantic similarity are concatenated to form the pair input representations to a Random Forest classifier whose task is to predict the miRNA-disease association probabilities. We present large-scale comparative experiments, ablation, and case studies to showcase our approach’s superiority. Besides, we make the model prediction results for 1618 miRNAs and 3679 diseases, along with all related information, publicly available at http://software.mpm.leibniz-ai-lab.de/ to foster assessments and future adoption

Inferring Disease-Associated MicroRNAs Using Semi-supervised Multi-Label Graph Convolutional Networks

Disease; Gene Network; Biocomputational Method; Computer ModelingMicroRNAs (miRNAs) play crucial roles in biological processes involved in diseases. The associations between diseases and protein-coding genes (PCGs) have been well investigated, and miRNAs interact with PCGs to trigger them to be functional. We present a computational method, DimiG, to infer miRNA-associated diseases using a semi-supervised Graph Convolutional Network model (GCN). DimiG uses a multi-label framework to integrate PCG-PCG interactions, PCG-miRNA interactions, PCG-disease associations, and tissue expression profiles. DimiG is trained on disease-PCG associations and an interaction network using a GCN, which is further used to score associations between diseases and miRNAs. We evaluate DimiG on a benchmark set from verified disease-miRNA associations. Our results demonstrate that DimiG outperforms the best unsupervised method and is comparable to two supervised methods. Three case studies of prostate cancer, lung cancer, and inflammatory bowel disease further demonstrate the efficacy of DimiG, where top miRNAs predicted by DimiG are supported by literature

A network-based approach to uncover microRNA-mediated disease comorbidities and potential pathobiological implications.

Disease-disease relationships (e.g., disease comorbidities) play crucial roles in pathobiological manifestations of diseases and personalized approaches to managing those conditions. In this study, we develop a network-based methodology, termed meta-path-based Disease Network (mpDisNet) capturing algorithm, to infer disease-disease relationships by assembling four biological networks: disease-miRNA, miRNA-gene, disease-gene, and the human protein-protein interactome. mpDisNet is a meta-path-based random walk to reconstruct the heterogeneous neighbors of a given node. mpDisNet uses a heterogeneous skip-gram model to solve the network representation of the nodes. We find that mpDisNet reveals high performance in inferring clinically reported disease-disease relationships, outperforming that of traditional gene/miRNA-overlap approaches. In addition, mpDisNet identifies network-based comorbidities for pulmonary diseases driven by underlying miRNA-mediated pathobiological pathways (i.e., hsa-let-7a- or hsa-let-7b-mediated airway epithelial apoptosis and pro-inflammatory cytokine pathways) as derived from the human interactome network analysis. The mpDisNet offers a powerful tool for network-based identification of disease-disease relationships with miRNA-mediated pathobiological pathways

A Meta-Path-Based Prediction Method for Human miRNA-Target Association

MicroRNAs (miRNAs) are short noncoding RNAs that play important roles in regulating gene expressing, and the perturbed miRNAs are often associated with development and tumorigenesis as they have effects on their target mRNA. Predicting potential miRNA-target associations from multiple types of genomic data is a considerable problem in the bioinformatics research. However, most of the existing methods did not fully use the experimentally validated miRNA-mRNA interactions. Here, we developed RMLM and RMLMSe to predict the relationship between miRNAs and their targets. RMLM and RMLMSe are global approaches as they can reconstruct the missing associations for all the miRNA-target simultaneously and RMLMSe demonstrates that the integration of sequence information can improve the performance of RMLM. In RMLM, we use RM measure to evaluate different relatedness between miRNA and its target based on different meta-paths; logistic regression and MLE method are employed to estimate the weight of different meta-paths. In RMLMSe, sequence information is utilized to improve the performance of RMLM. Here, we carry on fivefold cross validation and pathway enrichment analysis to prove the performance of our methods. The fivefold experiments show that our methods have higher AUC scores compared with other methods and the integration of sequence information can improve the performance of miRNA-target association prediction

LncRNA-Disease Association Prediction Using Two-Side Sparse Self-Representation

Evidences increasingly indicate the involvement of long non-coding RNAs (lncRNAs) in various biological processes. As the mutations and abnormalities of lncRNAs are closely related to the progression of complex diseases, the identification of lncRNA-disease associations has become an important step toward the understanding and treatment of diseases. Since only a limited number of lncRNA-disease associations have been validated, an increasing number of computational approaches have been developed for predicting potential lncRNA-disease associations. However, how to predict potential associations precisely through computational approaches remains challenging. In this study, we propose a novel two-side sparse self-representation (TSSR) algorithm for lncRNA-disease association prediction. By learning the self-representations of lncRNAs and diseases from known lncRNA-disease associations adaptively, and leveraging the information provided by known lncRNA-disease associations and the intra-associations among lncRNAs and diseases derived from other existing databases, our model could effectively utilize the estimated representations of lncRNAs and diseases to predict potential lncRNA-disease associations. The experiment results on three real data sets demonstrate that our TSSR outperforms other competing methods significantly. Moreover, to further evaluate the effectiveness of TSSR in predicting potential lncRNAs-disease associations, case studies of Melanoma, Glioblastoma, and Glioma are carried out in this paper. The results demonstrate that TSSR can effectively identify some candidate lncRNAs associated with these three diseases