Data Mining - Concepts and Techniques.

A novel coronavirus, formally named as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused coronavirus disease 2019 (COVID-19) worldwide, and it is the latest pandemic in the se...

Computational studies of drug repurposing and synergism of lopinavir, oseltamivir and ritonavir binding with SARS-CoV-2 protease against COVID-19.

Progresses in mass spectrometric instrumentation and bioinformatics identification algorithms made over the past decades allow quantitative measurements of relative or absolute protein/metabolite amounts in cells in a high-throughput manner, which has significantly expedited the exploration into functions and dynamics of complex biological systems. However, interpretation of high-throughput data is often restricted by the limited availability of suitable computational methods and enough statistical power. While many computational methodologies have been developed in the past decades to address the issue, it becomes clear that network-focused rather than individual gene/protein-focused strategies would be more appropriate to obtain a complete picture of cellular responses. Recently, an R analytical package named as weighted gene coexpression network analysis (WGCNA) was developed and applied to high-throughput microarray or RNA-seq datasets since it provides a systems-level insights, high sensitivity to low abundance, or small fold changes genes without any information loss. The approach was also recently applied to proteomic and metabolomic data analysis. However, due to the fact that low coverage of the current proteomic and metabolomic analytical technologies, causing the format of datasets are often incomplete, the method needs to be modified so that it can be properly utilized for meaningful biologically interpretation. In this chapter, we provide a detailed introduction of the modified protocol and its tutorials for applying the WGCNA approach in analyzing proteomic and metabolomic datasets.

WGCNA Application to Proteomic and Metabolomic Data Analysis.

Dimensionality reduction methods, also known as projections, are frequently used in multidimensional data exploration in machine learning, data science, and information visualization. Tens of such techniques have been proposed, aiming to address a wide set of requirements, such as ability to show the high-dimensional data structure, distance or neighborhood preservation, computational scalability, stability to data noise and/or outliers, and practical ease of use. However, it is far from clear for practitioners how to choose the best technique for a given use context. We present a survey of a wide body of projection techniques that helps answering this question. For this, we characterize the input data space, projection techniques, and the quality of projections, by several quantitative metrics. We sample these three spaces according to these metrics, aiming at good coverage with bounded effort. We describe our measurements and outline observed dependencies of the measured variables. Based on these results, we draw several conclusions that help comparing projection techniques, explain their results for different types of data, and ultimately help practitioners when choosing a projection for a given context. Our methodology, datasets, projection implementations, metrics, visualizations, and results are publicly open, so interested stakeholders can examine and/or extend this benchmark.

Toward a Quantitative Survey of Dimension Reduction Techniques

Identification of new drug-target interactions (DTIs) is an important but a time-consuming and costly step in drug discovery. In recent years, to mitigate these drawbacks, researchers have sought to identify DTIs using computational approaches. However, most existing methods construct drug networks and target networks separately, and then predict novel DTIs based on known associations between the drugs and targets without accounting for associations between drug-protein pairs (DPPs). To incorporate the associations between DPPs into DTI modeling, we built a DPP network based on multiple drugs and proteins in which DPPs are the nodes and the associations between DPPs are the edges of the network. We then propose a novel learning-based framework, 'graph convolutional network (GCN)-DTI', for DTI identification. The model first uses a graph convolutional network to learn the features for each DPP. Second, using the feature representation as an input, it uses a deep neural network to predict the final label. The results of our analysis show that the proposed framework outperforms some state-of-the-art approaches by a large margin.

Identifying drug–target interactions based on graph convolutional network and deep neural network

Drug discovery is a time-consuming, high-investment, and high-risk process in traditional drug development. Drug repositioning has become a popular strategy in recent years. Different from traditional drug development strategies, the strategy is efficient, economical and riskless. There are usually three kinds of approaches: computational approaches, biological experimental approaches, and mixed approaches, all of which are widely used in drug repositioning. In this paper, we reviewed computational approaches and highlighted their characteristics to provide references for researchers to develop more powerful approaches. At the same time, the important findings obtained using these approaches are listed. Furthermore, we summarized 76 important resources about drug repositioning. Finally, challenges and opportunities in drug repositioning are discussed from multiple perspectives, including technology, commercial models, patents and investment.

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Review of Drug Repositioning Approaches and Resources.

Dimensionality reduction techniques play important roles in the analysis of big data. Traditional dimensionality reduction approaches, such as principal component analysis (PCA) and linear discriminant analysis (LDA), have been studied extensively in the past few decades. However, as the dimensionality of data increases, the computational cost of traditional dimensionality reduction methods grows exponentially, and the computation becomes prohibitively intractable. These drawbacks have triggered the development of random projection (RP) techniques, which map high-dimensional data onto a low-dimensional subspace with extremely reduced time cost. However, the RP transformation matrix is generated without considering the intrinsic structure of the original data and usually leads to relatively high distortion. Therefore, in recent years, methods based on RP have been proposed to address this problem. In this paper, we summarize the methods used in different situations to help practitioners to employ the proper techniques for their specific applications. Meanwhile, we enumerate the benefits and limitations of the various methods and provide further references for researchers to develop novel RP-based approaches.

A survey of dimensionality reduction techniques based on random projection.

Biological pathways play important roles in the development of complex diseases, such as cancers, which are multifactorial complex diseases that are generally caused by mutation of multiple genes or dysregulation of pathways. It has become one of the most important issues to analyze pathways through combining multiple types of high-throughput data, such as genomics and proteomics, to understand the mechanisms of complex diseases. Currently, several network-based pathway analysis methods have been proposed. In this overview, we review seven major network-based pathway analysis methods and enumerate their benefits and limitations from an algorithmic perspective to provide a reference for the next generation of pathway analysis methods. Finally, we discuss the challenges that the next generation of methods faces.

Network-based methods for identifying critical pathways of complex diseases: a survey.

Pathway analysis combining multiple types of high-throughput data, such as genomics and proteomics, has become the first choice to gain insights into the pathogenesis of complex diseases. Currently, several pathway analysis methods have been developed to study complex diseases. However, these methods did not take into account the interaction between internal and external genes of the pathway and between pathways. Hence, these approaches still face some challenges. Here, we propose a network-based pathway-expanding approach that takes the topological structures of biological networks into account. First, two weighted gene-gene interaction networks (tumor and normal) are constructed integrating protein-protein interaction(PPI) information, gene expression data and pathway databases. Then, they are used to identify significant pathways through testing the difference of topological structures of expanded pathways in the two weighted networks. The proposed method is employed to analyze two breast cancer data. As a result, the top 15 pathways identified using the proposed method are supported by biological knowledge from the published literatures and other methods. In addition, the proposed method is also compared with other methods, such as GSEA and SPIA, and estimated using the classification performance of the top 15 expanded pathways. A novel network-based pathway-expanding approach is proposed to avoid the limitations of existing pathway analysis approaches. Experimental results indicate that the proposed method can accurately and reliably identify significant pathways which are related to the corresponding disease.

/pdf/a-network-based-pathway-expanding-approach-for-pathway-21reioib8j.pdf

Hanqing Xue

Papers

Review of Drug Repositioning Approaches and Resources.

A survey of dimensionality reduction techniques based on random projection.

Network-based methods for identifying critical pathways of complex diseases: a survey.

A network-based pathway-expanding approach for pathway analysis