RANDOM WALK APPLIED TO HETEROGENOUS DRUG-TARGET NETWORKS FOR PREDICTING BIOLOGICAL OUTCOMES

Thesis (Ph.D.) - Indiana University, Informatics and Computing, 2016Prediction of unknown drug target interactions from bioassay data is critical not only for the understanding of various interactions but also crucial for the development of new drugs and repurposing of old ones. Conventional methods for prediction of such interactions can be divided into 2D based and 3D based methods. 3D methods are more CPU expensive and require more manual interpretation whereas 2D methods are actually fast methods like machine learning and similarity search which use chemical fingerprints. One of the problems of using traditional machine learning based method to predict drug-target pairs is that it requires a labeled information of true and false interactions. One of the major problems of supervised learning methods is selection on negative samples. Unknown drug target interactions are regarded as false interactions, which may influence the predictive accuracy of the model. To overcome this problem network based methods has become an effective tool in predicting the drug target interactions overcoming the negative sampling problem. In this dissertation study, I will describe traditional machine learning methods and 3D methods of pharmacophore modeling for drug target prediction and will show how these methods work in a drug discovery scenario. I will then introduce a new framework for drug target prediction based on bipartite networks of drug target relations known as Random Walk with Restart (RWR). RWR integrates various networks including drug– drug similarity networks, protein-protein similarity networks and drug- target interaction networks into a heterogeneous network that is capable of predicting novel drug-target relations. I will describe how chemical features for measuring drug-drug similarity do not affect performance in predicting interactions and further show the performance of RWR using an external dataset from ChEMBL database. I will describe about further implementations of RWR approach into multilayered networks consisting of biological data like diseases, tissue based gene expression data, protein- complexes and metabolic pathways to predict associations between human diseases and metabolic pathways which are very crucial in drug discovery. I have further developed a software tool package netpredictor in R (standalone and the web) for unipartite and bipartite networks and implemented network-based predictive algorithms and network properties for drug-target prediction. This package will be described

Random Walks: A Review of Algorithms and Applications

A random walk is known as a random process which describes a path including a succession of random steps in the mathematical space. It has increasingly been popular in various disciplines such as mathematics and computer science. Furthermore, in quantum mechanics, quantum walks can be regarded as quantum analogues of classical random walks. Classical random walks and quantum walks can be used to calculate the proximity between nodes and extract the topology in the network. Various random walk related models can be applied in different fields, which is of great significance to downstream tasks such as link prediction, recommendation, computer vision, semi-supervised learning, and network embedding. In this paper, we aim to provide a comprehensive review of classical random walks and quantum walks. We first review the knowledge of classical random walks and quantum walks, including basic concepts and some typical algorithms. We also compare the algorithms based on quantum walks and classical random walks from the perspective of time complexity. Then we introduce their applications in the field of computer science. Finally we discuss the open issues from the perspectives of efficiency, main-memory volume, and computing time of existing algorithms. This study aims to contribute to this growing area of research by exploring random walks and quantum walks together.Comment: 13 pages, 4 figure

Heterogeneous Multi-Layered Network Model for Omics Data Integration and Analysis

Advances in next-generation sequencing and high-throughput techniques have enabled the generation of vast amounts of diverse omics data. These big data provide an unprecedented opportunity in biology, but impose great challenges in data integration, data mining, and knowledge discovery due to the complexity, heterogeneity, dynamics, uncertainty, and high-dimensionality inherited in the omics data. Network has been widely used to represent relations between entities in biological system, such as protein-protein interaction, gene regulation, and brain connectivity (i.e. network construction) as well as to infer novel relations given a reconstructed network (aka link prediction). Particularly, heterogeneous multi-layered network (HMLN) has proven successful in integrating diverse biological data for the representation of the hierarchy of biological system. The HMLN provides unparalleled opportunities but imposes new computational challenges on establishing causal genotype-phenotype associations and understanding environmental impact on organisms. In this review, we focus on the recent advances in developing novel computational methods for the inference of novel biological relations from the HMLN. We first discuss the properties of biological HMLN. Then we survey four categories of state-of-the-art methods (matrix factorization, random walk, knowledge graph, and deep learning). Thirdly, we demonstrate their applications to omics data integration and analysis. Finally, we outline strategies for future directions in the development of new HMLN models

Leveraging Trust Relations to Improve Academic Patent Recommendation

Academic patent trading is one of the important ways for university technology transfer. Compared to industry patent trading, academic patent trading suffers from a more serious information asymmetric problem. It needs a recommendation service to help companies identify academic patents that they want to pay. However, existing recommendation approaches have limitations in facilitating academic patent trading in online patent platforms because most of them only consider patent-level characteristics. A high trust degree of a company towards academic patents can alleviate the information asymmetry and encourage trading. This study proposes a novel academic patent recommendation approach with a hybrid strategy, combining citation-based relevance, connectivity, and trustworthiness. An offline experiment is conducted to evaluate the performance of the proposed recommendation approach. The results show that the proposed method performs better than the baseline methods in both accuracy and ranking