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

Prediction of lncRNA-Disease Associations Based on Inductive Matrix Completion

Motivation: Accumulating evidences indicate that long non-coding RNAs (lncRNAs) play pivotal roles in various biological processes. Mutations and dysregulations of lncRNAs are implicated in miscellaneous human diseases. Predicting lncRNA–disease associations is beneficial to disease diagnosis as well as treatment. Although many computational methods have been developed, precisely identifying lncRNA–disease associations, especially for novel lncRNAs, remains challenging. Results: In this study, we propose a method (named SIMCLDA) for predicting potential lncRNA– disease associations based on inductive matrix completion. We compute Gaussian interaction profile kernel of lncRNAs from known lncRNA–disease interactions and functional similarity of diseases based on disease–gene and gene–gene onotology associations. Then, we extract primary feature vectors from Gaussian interaction profile kernel of lncRNAs and functional similarity of diseases by principal component analysis, respectively. For a new lncRNA, we calculate the interaction profile according to the interaction profiles of its neighbors. At last, we complete the association matrix based on the inductive matrix completion framework using the primary feature vectors from the constructed feature matrices. Computational results show that SIMCLDA can effectively predict lncRNA–disease associations with higher accuracy compared with previous methods. Furthermore, case studies show that SIMCLDA can effectively predict candidate lncRNAs for renal cancer, gastric cancer and prostate cancer

Identifying disease-associated genes based on artificial intelligence

Identifying disease-gene associations can help improve the understanding of disease mechanisms, which has a variety of applications, such as early diagnosis and drug development. Although experimental techniques, such as linkage analysis, genome-wide association studies (GWAS), have identified a large number of associations, identifying disease genes is still challenging since experimental methods are usually time-consuming and expensive. To solve these issues, computational methods are proposed to predict disease-gene associations. Based on the characteristics of existing computational algorithms in the literature, we can roughly divide them into three categories: network-based methods, machine learning-based methods, and other methods. No matter what models are used to predict disease genes, the proper integration of multi-level biological data is the key to improving prediction accuracy. This thesis addresses some limitations of the existing computational algorithms, and integrates multi-level data via artificial intelligence techniques. The thesis starts with a comprehensive review of computational methods, databases, and evaluation methods used in predicting disease-gene associations, followed by one network-based method and four machine learning-based methods. The first chapter introduces the background information, objectives of the studies and structure of the thesis. After that, a comprehensive review is provided in the second chapter to discuss the existing algorithms as well as the databases and evaluation methods used in existing studies. Having the objectives and future directions, the thesis then presents five computational methods for predicting disease-gene associations. The first method proposed in Chapter 3 considers the issue of non-disease gene selection. A shortest path-based strategy is used to select reliable non-disease genes from a disease gene network and a differential network. The selected genes are then used by a network-energy model to improve its performance. The second method proposed in Chapter 4 constructs sample-based networks for case samples and uses them to predict disease genes. This strategy improves the quality of protein-protein interaction (PPI) networks, which further improves the prediction accuracy. Chapter 5 presents a generic model which applies multimodal deep belief nets (DBN) to fuse different types of data. Network embeddings extracted from PPI networks and gene ontology (GO) data are fused with the multimodal DBN to obtain cross-modality representations. Chapter 6 presents another deep learning model which uses a convolutional neural network (CNN) to integrate gene similarities with other types of data. Finally, the fifth method proposed in Chapter 7 is a nonnegative matrix factorization (NMF)-based method. This method maps diseases and genes onto a lower-dimensional manifold, and the geodesic distance between diseases and genes are used to predict their associations. The method can predict disease genes even if the disease under consideration has no known associated genes. In summary, this thesis has proposed several artificial intelligence-based computational algorithms to address the typical issues existing in computational algorithms. Experimental results have shown that the proposed methods can improve the accuracy of disease-gene prediction

Dual Convolutional Neural Networks With Attention Mechanisms Based Method for Predicting Disease-Related lncRNA Genes

A lot of studies indicated that aberrant expression of long non-coding RNA genes (lncRNAs) is closely related to human diseases. Identifying disease-related lncRNAs (disease lncRNAs) is critical for understanding the pathogenesis and etiology of diseases. Most of the previous methods focus on prioritizing the potential disease lncRNAs based on shallow learning methods. The methods fail to extract the deep and complex feature representations of lncRNA-disease associations. Furthermore, nearly all the methods ignore the discriminative contributions of the similarity, association, and interaction relationships among lncRNAs, disease, and miRNAs for the association prediction. A dual convolutional neural networks with attention mechanisms based method is presented for predicting the candidate disease lncRNAs, and it is referred to as CNNLDA. CNNLDA deeply integrates the multiple source data like the lncRNA similarities, the disease similarities, the lncRNA-disease associations, the lncRNA-miRNA interactions, and the miRNA-disease associations. The diverse biological premises about lncRNAs, miRNAs, and diseases are combined to construct the feature matrix from the biological perspectives. A novel framework based on the dual convolutional neural networks is developed to learn the global and attention representations of the lncRNA-disease associations. The left part of the framework exploits the various information contained by the feature matrix to learn the global representation of lncRNA-disease associations. The different connection relationships among the lncRNA, miRNA, and disease nodes and the different features of these nodes have the discriminative contributions for the association prediction. Hence we present the attention mechanisms from the relationship level and the feature level respectively, and the right part of the framework learns the attention representation of associations. The experimental results based on the cross validation indicate that CNNLDA yields superior performance than several state-of-the-art methods. Case studies on stomach cancer, lung cancer, and colon cancer further demonstrate CNNLDA's ability to discover the potential disease lncRNAs

Polygenic Risk Score for Cardiovascular Diseases in Artificial Intelligence Paradigm: A Review

Cardiovascular disease (CVD) related mortality and morbidity heavily strain society. The relationship between external risk factors and our genetics have not been well established. It is widely acknowledged that environmental influence and individual behaviours play a significant role in CVD vulnerability, leading to the development of polygenic risk scores (PRS). We employed the PRISMA search method to locate pertinent research and literature to extensively review artificial intelligence (AI)-based PRS models for CVD risk prediction. Furthermore, we analyzed and compared conventional vs. AI-based solutions for PRS. We summarized the recent advances in our understanding of the use of AI-based PRS for risk prediction of CVD. Our study proposes three hypotheses: i) Multiple genetic variations and risk factors can be incorporated into AI-based PRS to improve the accuracy of CVD risk predicting. ii) AI-based PRS for CVD circumvents the drawbacks of conventional PRS calculators by incorporating a larger variety of genetic and non-genetic components, allowing for more precise and individualised risk estimations. iii) Using AI approaches, it is possible to significantly reduce the dimensionality of huge genomic datasets, resulting in more accurate and effective disease risk prediction models. Our study highlighted that the AI-PRS model outperformed traditional PRS calculators in predicting CVD risk. Furthermore, using AI-based methods to calculate PRS may increase the precision of risk predictions for CVD and have significant ramifications for individualized prevention and treatment plans

Polygenic Risk Score for Cardiovascular Diseases in Artificial Intelligence Paradigm

Cardiovascular disease (CVD) related mortality and morbidity heavily strain society. The relationship between external risk factors and our genetics have not been well established. It is widely acknowledged that environmental influence and individual behaviours play a significant role in CVD vulnerability, leading to the development of polygenic risk scores (PRS). We employed the PRISMA search method to locate pertinent research and literature to extensively review artificial intelligence (AI)-based PRS models for CVD risk prediction. Furthermore, we analyzed and compared conventional vs. AI-based solutions for PRS. We summarized the recent advances in our understanding of the use of AI-based PRS for risk prediction of CVD. Our study proposes three hypotheses: i) Multiple genetic variations and risk factors can be incorporated into AI-based PRS to improve the accuracy of CVD risk predicting. ii) AI-based PRS for CVD circumvents the drawbacks of conventional PRS calculators by incorporating a larger variety of genetic and non-genetic components, allowing for more precise and individualised risk estimations. iii) Using AI approaches, it is possible to significantly reduce the dimensionality of huge genomic datasets, resulting in more accurate and effective disease risk prediction models. Our study highlighted that the AI-PRS model outperformed traditional PRS calculators in predicting CVD risk. Furthermore, using AI-based methods to calculate PRS may increase the precision of risk predictions for CVD and have significant ramifications for individualized prevention and treatment plans

Application of Machine Learning in Microbiology

Microorganisms are ubiquitous and closely related to people’s daily lives. Since they were first discovered in the 19th century, researchers have shown great interest in microorganisms. People studied microorganisms through cultivation, but this method is expensive and time consuming. However, the cultivation method cannot keep a pace with the development of high-throughput sequencing technology. To deal with this problem, machine learning (ML) methods have been widely applied to the field of microbiology. Literature reviews have shown that ML can be used in many aspects of microbiology research, especially classification problems, and for exploring the interaction between microorganisms and the surrounding environment. In this study, we summarize the application of ML in microbiology

DlncRNALoc: A discrete wavelet transform-based model for predicting lncRNA subcellular localization

The prediction of long non-coding RNA (lncRNA) subcellular localization is essential to the understanding of its function and involvement in cellular regulation. Traditional biological experimental methods are costly and time-consuming, making computational methods the preferred approach for predicting lncRNA subcellular localization (LSL). However, existing computational methods have limitations due to the structural characteristics of lncRNAs and the uneven distribution of data across subcellular compartments. We propose a discrete wavelet transform (DWT)-based model for predicting LSL, called DlncRNALoc. We construct a physicochemical property matrix of a 2-tuple bases based on lncRNA sequences, and we introduce a DWT lncRNA feature extraction method. We use the Synthetic Minority Over-sampling Technique (SMOTE) for oversampling and the local fisher discriminant analysis (LFDA) algorithm to optimize feature information. The optimized feature vectors are fed into support vector machine (SVM) to construct a predictive model. DlncRNALoc has been applied for a five-fold cross-validation on the three sets of benchmark datasets. Extensive experiments have demonstrated the superiority and effectiveness of the DlncRNALoc model in predicting LSL

A review of multi-omics data integration through deep learning approaches for disease diagnosis, prognosis, and treatment

Accurate diagnosis is the key to providing prompt and explicit treatment and disease management. The recognized biological method for the molecular diagnosis of infectious pathogens is polymerase chain reaction (PCR). Recently, deep learning approaches are playing a vital role in accurately identifying disease-related genes for diagnosis, prognosis, and treatment. The models reduce the time and cost used by wet-lab experimental procedures. Consequently, sophisticated computational approaches have been developed to facilitate the detection of cancer, a leading cause of death globally, and other complex diseases. In this review, we systematically evaluate the recent trends in multi-omics data analysis based on deep learning techniques and their application in disease prediction. We highlight the current challenges in the field and discuss how advances in deep learning methods and their optimization for application is vital in overcoming them. Ultimately, this review promotes the development of novel deep-learning methodologies for data integration, which is essential for disease detection and treatment