Identifying Essential Hub Genes and Protein Complexes in Malaria GO Data using Semantic Similarity Measures

Hub genes play an essential role in biological systems because of their interaction with other genes. A vocabulary used in bioinformatics called Gene Ontology (GO) describes how genes and proteins operate. This flexible ontology illustrates the operation of molecular, biological, and cellular processes (Pmol, Pbio, Pcel). There are various methodologies that can be analyzed to determine semantic similarity. Research in this study, we employ the jack-knife method by taking into account 4 well-liked Semantic similarity measures namely Jaccard similarity, Cosine similarity, Pairsewise document similarity, and Levenshtein distance. Based on these similarity values, the protein-protein interaction network (PPI) of Malaria GO (Gene Ontology) data is built, which causes clusters of identical or related protein complexes (Px) to form. The hub nodes of the network are these necessary proteins. We use a variety of centrality measures to establish clusters of these networks in order to determine which node is the most important. The clusters' unique formation makes it simple to determine which class of Px they are allied to.Comment: 23 pages, 15 figure

Computational Approaches for Predicting Drug Targets

This thesis reports the development of several computational approaches to predict human disease proteins and to assess their value as drug targets, using in-house domain functional families (CATH FunFams). CATH-FunFams comprise evolutionary related protein domains with high structural and functional similarity. External resources were used to identify proteins associated with disease and their genetic variations. These were then mapped to the CATH-FunFams together with information on drugs bound to any relatives within the FunFam. A number of novel approaches were then used to predict the proteins likely to be driving disease and to assess whether drugs could be repurposed within the FunFams for targeting these putative driver proteins. The first work chapter of this thesis reports the mapping of drugs to CATHFunFams to identify druggable FunFams based on statistical overrepresentation of drug targets within the FunFam. 81 druggable CATH-FunFams were identified and the dispersion of their relatives on a human protein interaction network was analysed to assess their propensity to be associated with side effects. In the second work chapter, putative drug targets for bladder cancer were identified using a novel computational protocol that expands a set of known bladder cancer genes with genes highly expressed in bladder cancer and highly associated with known bladder cancer genes in a human protein interaction network. 35 new bladder cancer targets were identified in druggable FunFams, for some of which FDA approved drugs could be repurposed from other protein domains in the FunFam. In the final work chapter, protein kinases and kinase inhibitors were analysed. These are an important class of human drug targets. A novel classification protocol was applied to give a comprehensive classification of the kinases which was benchmarked and compared with other widely used kinase classifications. Druginformation from ChEMBL was mapped to the Kinase-FunFams and analyses of protein network characteristics of the kinase relatives in each FunFam used to identify those families likely to be associated with side effects

A survey of statistical network models

Networks are ubiquitous in science and have become a focal point for discussion in everyday life. Formal statistical models for the analysis of network data have emerged as a major topic of interest in diverse areas of study, and most of these involve a form of graphical representation. Probability models on graphs date back to 1959. Along with empirical studies in social psychology and sociology from the 1960s, these early works generated an active network community and a substantial literature in the 1970s. This effort moved into the statistical literature in the late 1970s and 1980s, and the past decade has seen a burgeoning network literature in statistical physics and computer science. The growth of the World Wide Web and the emergence of online networking communities such as Facebook, MySpace, and LinkedIn, and a host of more specialized professional network communities has intensified interest in the study of networks and network data. Our goal in this review is to provide the reader with an entry point to this burgeoning literature. We begin with an overview of the historical development of statistical network modeling and then we introduce a number of examples that have been studied in the network literature. Our subsequent discussion focuses on a number of prominent static and dynamic network models and their interconnections. We emphasize formal model descriptions, and pay special attention to the interpretation of parameters and their estimation. We end with a description of some open problems and challenges for machine learning and statistics.Comment: 96 pages, 14 figures, 333 reference

A Framework for Personalized Content Recommendations to Support Informal Learning in Massively Diverse Information WIKIS

Personalization has proved to achieve better learning outcomes by adapting to specific learners’ needs, interests, and/or preferences. Traditionally, most personalized learning software systems focused on formal learning. However, learning personalization is not only desirable for formal learning, it is also required for informal learning, which is self-directed, does not follow a specified curriculum, and does not lead to formal qualifications. Wikis among other informal learning platforms are found to attract an increasing attention for informal learning, especially Wikipedia. The nature of wikis enables learners to freely navigate the learning environment and independently construct knowledge without being forced to follow a predefined learning path in accordance with the constructivist learning theory. Nevertheless, navigation on information wikis suffer from several limitations. To support informal learning on Wikipedia and similar environments, it is important to provide easy and fast access to relevant content. Recommendation systems (RSs) have long been used to effectively provide useful recommendations in different technology enhanced learning (TEL) contexts. However, the massive diversity of unstructured content as well as user base on such information oriented websites poses major challenges when designing recommendation models for similar environments. In addition to these challenges, evaluation of TEL recommender systems for informal learning is rather a challenging activity due to the inherent difficulty in measuring the impact of recommendations on informal learning with the absence of formal assessment and commonly used learning analytics. In this research, a personalized content recommendation framework (PCRF) for information wikis as well as an evaluation framework that can be used to evaluate the impact of personalized content recommendations on informal learning from wikis are proposed. The presented recommendation framework models learners’ interests by continuously extrapolating topical navigation graphs from learners’ free navigation and applying graph structural analysis algorithms to extract interesting topics for individual users. Then, it integrates learners’ interest models with fuzzy thesauri for personalized content recommendations. Our evaluation approach encompasses two main activities. First, the impact of personalized recommendations on informal learning is evaluated by assessing conceptual knowledge in users’ feedback. Second, web analytics data is analyzed to get an insight into users’ progress and focus throughout the test session. Our evaluation revealed that PCRF generates highly relevant recommendations that are adaptive to changes in user’s interest using the HARD model with rank-based mean average precision (MAP@k) scores ranging between 100% and 86.4%. In addition, evaluation of informal learning revealed that users who used Wikipedia with personalized support could achieve higher scores on conceptual knowledge assessment with average score of 14.9 compared to 10.0 for the students who used the encyclopedia without any recommendations. The analysis of web analytics data show that users who used Wikipedia with personalized recommendations visited larger number of relevant pages compared to the control group, 644 vs 226 respectively. In addition, they were also able to make use of a larger number of concepts and were able to make comparisons and state relations between concepts

Computation in Complex Networks

Complex networks are one of the most challenging research focuses of disciplines, including physics, mathematics, biology, medicine, engineering, and computer science, among others. The interest in complex networks is increasingly growing, due to their ability to model several daily life systems, such as technology networks, the Internet, and communication, chemical, neural, social, political and financial networks. The Special Issue “Computation in Complex Networks" of Entropy offers a multidisciplinary view on how some complex systems behave, providing a collection of original and high-quality papers within the research fields of: • Community detection • Complex network modelling • Complex network analysis • Node classification • Information spreading and control • Network robustness • Social networks • Network medicin

Micro-, Meso- and Macro-Connectomics of the Brain

Neurosciences, Neurolog