Computational Methods for Processing and Analysis of Biological Pathways

Abstract

This work offers a guided walkthrough of one of the most promising research areas in modern life sciences, enabling a deeper understanding of involved concepts and methodologies via an interdisciplinary view, focusing on both well-established approaches and cutting-edge research. Highlighting what pathway analysis can offer to both the experimentalist and the modeler, the text opens with an introduction to a general methodology that outlines common workflows shared by several methods. This is followed by a review of pathway and sub-pathway based approaches for systems pharmacology. The work then presents an overview of pathway analysis methods developed to model the temporal aspects of drug- or disease-induced perturbations and extract relevant dynamic themes. The text concludes by discussing several state-of-the-art methods in pathway analysis, which address the important problem of identifying differentially expressed pathways and sub-pathways. Preface; Contents; 1 Introduction; Abstract; 1.1 Biological Networks; 1.1.1 Properties; 1.1.2 Categories of Biological Networks; 1.2 Pathway Analysis; 1.2.1 Methodology; 1.2.2 Evolution of Pathway Analysis Methods; 1.3 Systems Pharmacology; References; 2 Networks and Pathways in Systems Pharmacology; Abstract; 2.1 Introduction; 2.2 Network- and Pathway/Sub-pathway-Based Characterization of Drugs Mechanism of Action; 2.3 Identification of New Drug Targets and Polypharmacology Applications; 2.3.1 Target Characterization and Identification Using Network Properties of Drug Targets. 2.3.2 Identification of Drug Targets Based on Integrative Network Approaches2.3.3 Network-Based Polypharmacology; 2.4 Network-Based Drug Repositioning; 2.4.1 Drug Repositioning Based on Molecular Profiles; 2.4.2 Drug Repositioning Based on Phenotypic Profiles; 2.5 Network-Based Side Effect Modeling and Prediction; 2.5.1 Approaches Based on Chemical Structure; 2.5.2 Approaches Based on Pathways/Sub-pathways; 2.6 Current Challenges and Future Considerations; References; 3 Time-Varying Methods for Pathway and Sub-pathway Analysis; Abstract; 3.1 Introduction. 3.2 Conversion of Pathway Databases to Graphs3.3 Time-Varying Pathway and Sub-pathway Extraction; 3.3.1 Linear Sub-pathway Extraction; 3.3.2 Nonlinear Sub-pathway Extraction; 3.4 Temporal Dynamics Scoring Schemes; 3.4.1 Approach Followed in CHRONOS; 3.4.2 Other Approaches; 3.5 Synthetic and Biological Data Analysis Results; References; 4 Identification of Differentially Expressed Pathways and Sub-pathways; Abstract; 4.1 Introduction; 4.2 Approaches Based on Gene Sets; 4.3 Approaches Based on Pathway Topology; 4.4 Conversion of Pathway Databases Information to Graphs. 4.5 Gene and Pathway-Level Statistics of Differential Expression4.5.1 Methods Using Experimental Data for Sub-pathway Identification; 4.5.2 Methods Using Experimental Data for Evaluating the Statistical Significance of Sub-pathways; 4.6 DEsubs: A Flexible Tool for Identification of Differentially Expressed Sub-pathways; References.