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

Machine Learning Methods for Effectively Discovering Complex Relationships in Graph Data

Graphs are extensively employed in many systems due to their capability to capture the interactions (edges) among data (nodes) in many real-life scenarios. Social networks, biological networks and molecular graphs are some of the domains where data have inherent graph structural information. Built graphs can be used to make predictions in Machine Learning (ML) such as node classifications, link predictions, graph classifications, etc. But, existing ML algorithms hold a core assumption that data instances are independent of each other and hence prevent incorporating graph information into ML. This irregular and variable sized nature of non-Euclidean data makes learning underlying patterns of the graph more sophisticated. One approach is to convert the graph information into a lower dimensional space and use traditional learning methods on the reduced space. Meanwhile, Deep Learning has better performance than ML due to convolutional layers and recurrent layers which consider simple correlations in spatial and temporal data, respectively. This proves the importance of taking data interrelationships into account and Graph Convolutional Networks (GCNs) are inspired by this fact to exploit the structure of graphs to make better inference in both node-centric and graph-centric applications. In this dissertation, the graph based ML prediction is addressed in terms of both node classification and link prediction tasks. At first, GCN is thoroughly studied and compared with other graph embedding methods specific to biological networks. Next, we present several new GCN algorithms to improve the prediction performance related to biomedical networks and medical imaging tasks. A circularRNA (circRNA) and disease association network is modeled for both node classification and link prediction tasks to predict diseases relevant to circRNAs to demonstrate the effectiveness of graph convolutional learning. A GCN based chest X-ray image classification outperforms state-of-the-art transfer learning methods. Next, the graph representation is used to analyze the feature dependencies of data and select an optimal feature subset which respects the original data structure. Finally, the usability of this algorithm is discussed in identifying disease specific genes by exploiting gene-gene interactions

Multivariate Information Fusion With Fast Kernel Learning to Kernel Ridge Regression in Predicting LncRNA-Protein Interactions

Long non-coding RNAs (lncRNAs) constitute a large class of transcribed RNA molecules. They have a characteristic length of more than 200 nucleotides which do not encode proteins. They play an important role in regulating gene expression by interacting with the homologous RNA-binding proteins. Due to the laborious and time-consuming nature of wet experimental methods, more researchers should pay great attention to computational approaches for the prediction of lncRNA-protein interaction (LPI). An in-depth literature review in the state-of-the-art in silico investigations, leads to the conclusion that there is still room for improving the accuracy and velocity. This paper propose a novel method for identifying LPI by employing Kernel Ridge Regression, based on Fast Kernel Learning (LPI-FKLKRR). This approach, uses four distinct similarity measures for lncRNA and protein space, respectively. It is remarkable, that we extract Gene Ontology (GO) with proteins, in order to improve the quality of information in protein space. The process of heterogeneous kernels integration, applies Fast Kernel Learning (FastKL) to deal with weight optimization. The extrapolation model is obtained by gaining the ultimate prediction associations, after using Kernel Ridge Regression (KRR). Experimental outcomes show that the ability of modeling with LPI-FKLKRR has extraordinary performance compared with LPI prediction schemes. On benchmark dataset, it has been observed that the best Area Under Precision Recall Curve (AUPR) of 0.6950 is obtained by our proposed model LPI-FKLKRR, which outperforms the integrated LPLNP (AUPR: 0.4584), RWR (AUPR: 0.2827), CF (AUPR: 0.2357), LPIHN (AUPR: 0.2299), and LPBNI (AUPR: 0.3302). Also, combined with the experimental results of a case study on a novel dataset, it is anticipated that LPI-FKLKRR will be a useful tool for LPI prediction

Artificial intelligence in cancer target identification and drug discovery

Artificial intelligence is an advanced method to identify novel anticancer targets and discover novel drugs from biology networks because the networks can effectively preserve and quantify the interaction between components of cell systems underlying human diseases such as cancer. Here, we review and discuss how to employ artificial intelligence approaches to identify novel anticancer targets and discover drugs. First, we describe the scope of artificial intelligence biology analysis for novel anticancer target investigations. Second, we review and discuss the basic principles and theory of commonly used network-based and machine learning-based artificial intelligence algorithms. Finally, we showcase the applications of artificial intelligence approaches in cancer target identification and drug discovery. Taken together, the artificial intelligence models have provided us with a quantitative framework to study the relationship between network characteristics and cancer, thereby leading to the identification of potential anticancer targets and the discovery of novel drug candidates

A new computational framework for the classification and function prediction of long non-coding RNAs

Long non-coding RNAs (lncRNAs) are known to play a significant role in several biological processes. These RNAs possess sequence length greater than 200 base pairs (bp), and so are often misclassified as protein-coding genes. Most Coding Potential Computation (CPC) tools fail to accurately identify, classify and predict the biological functions of lncRNAs in plant genomes, due to previous research being limited to mammalian genomes. In this thesis, an investigation and extraction of various sequence and codon-bias features for identification of lncRNA sequences has been carried out, to develop a new CPC Framework. For identification of essential features, the framework implements regularisation-based selection. A novel classification algorithm is implemented, which removes the dependency on experimental datasets and provides a coordinate-based solution for sub-classification of lncRNAs. For imputing the lncRNA functions, lncRNA-protein interactions have been first determined through co-expression of genes which were re-analysed by a sequence similaritybased approach for identification of novel interactions and prediction of lncRNA functions in the genome. This integrates a D3-based application for visualisation of lncRNA sequences and their associated functions in the genome. Standard evaluation metrics such as accuracy, sensitivity, and specificity have been used for benchmarking the performance of the framework against leading CPC tools. Case study analyses were conducted with plant RNA-seq datasets for evaluating the effectiveness of the framework using a cross-validation approach. The tests show the framework can provide significant improvements on existing CPC models for plant genomes: 20-40% greater accuracy. Function prediction analysis demonstrates results are consistent with the experimentally-published findings

A Deep Learning Approach to LncRNA Subcellular Localization Using Inexact q-mer

Long non coding Ribonucleic Acids (lncRNAs) can be localized to different cellular components, such as the nucleus, exosome, cytoplasm, ribosome, etc. Their biological functions can be influenced by the region of the cell they are located. Many of these lncRNAs are associated with different challenging diseases. Thus, it is crucial to study their subcellular localization. However, compared to the vast number of lncRNAs, only relatively few have annotations in terms of their subcellular localization. Conventional computational methods use q-mer profiles from lncRNA sequences and then train machine learning models, such as support vector machines and logistic regression with the profiles. These methods focus on the exact q-mer. Given possible sequence mutations and other uncertainties in genomic sequences and their role in biological function, a consideration of these changes might improve our ability to model lncRNAs and their localization. I hypothesize that considering these changes may improve the ability to predict subcellular localization of lncRNAs. To test this hypothesis, I propose a deep learning model with inexact q-mers for the localization of lncRNAs in the cell. The proposed method can obtain a high overall accuracy of 94.7%, an average of 91.3% on a benchmark dataset, using the 8-mers with mismatches. In comparison, the exact 8-mer result was 89.8%. The proposed approach outperformed existing state-of-art lncRNA predictors on two different datasets. Therefore, the results support the hypothesis that deep learning models using inexact q-mers can improve the performance of computational lncRNA localization algorithms. The lengths of the lncRNAs vary from hundreds to thousands of nucleotides. In this work, I also check whether the length of lncRNA will impact the prediction accuracy. The results show that when the lncRNA sequence\u27s length is between 2000 and 3000 nucleotides, our model is more accurate

Development of New Bioinformatic Approaches for Human Genetic Studies

The development of bioinformatics methods for human genetic studies utilizes the vast amount of data to generate new valuable information. Machine learning and statistical coupling analysis can be used in the study of human diseases. These diseases include intellectual disabilities (ID), prevalent in 1-3% of the population and caused primarily by genetics. Although many cases of ID are caused by mutations in protein-coding genes, the possible involvement of long non-coding RNAs (lncRNAs) in ID due to their role in gene expression regulation, has been explored. In this study, we used machine learning to develop a new expression-based model trained using ID genes encoded with the developing brain transcriptome. The model was fine-tuned using the class-balancing approach of synthetic over-sampling of the minority class, resulting in improved performance. We used the model to predict candidate ID-associated lncRNAs. Our model identified several candidates that overlapped with previously reported ID-associated lncRNAs, enriched with neurodevelopmental functions, and highly expressed in brain tissues. Machine learning was also used to predict protein stability changes caused by missense mutations, which can lead to disease conditions including ID. We tested Random Forests, Support Vector Machines (SVM) and Naïve Bayes to find the best-performing algorithm to develop a multi-class classifier. We developed an SVM model using relevant physico-chemical features after feature selection. Our work identified new features for predicting the effect of amino acid substitutions on protein stability and a well-performing multi-class classifier solely based on sequence information. Statistical approaches were used to analyze the association between mutations and phenotypes. In this study, we used statistical coupling analysis (SCA) to cluster disease-causing mutations and ID phenotypes. Using SCA we identified groups of co-evolving residues, known as protein sectors, in ID protein families. Within each distinct sector, mutations associated with different phenotypic manifestations associated with a syndromic ID were identified. Our results suggest that protein sector analysis can be used to associate mutations with phenotypic manifestations in human diseases. The bioinformatic methods developed in this dissertation can be used in human genetic research to understand the role of new genes and proteins in human disease

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