Pathway Analysis for Drug Discovery

This book introduces drug researchers to the novel computational approaches of pathway analysis and explains the existing applications that can save time and money in the drug discovery process. It covers traditional computational methods and software for pathway analysis microarray, proteomics, and metabolomics. It explains pathway reconstruction of diseases and toxic states, pathway analysis in various phases, dynamic modeling of drug responses, and more. This is a core resource for drug discovery and pharmaceutical industry researchers, chemists, and biologists and for professionals in related fields.

Preface vii

Contributors ix

1 Introduction to Pathway Analysis 1
Anton Yuryev

2 Software Infrastructure and Data Model for Pathway Analysis 27
Fedor Bokov and Anton Yuryev

3 Automatic Pathway Inference in Heterogeneous Biological Association Networks 47
Anton Yuryev, Andrey Kalinin, and Nikolai Daraselia

4 Algorithmic Basis for Pathway Visualization 67
Sergey Simakov, Iaroslav Ispolatov, Sergei Maslov, and Alexander Nikitin

5 Pathway Analysis of High-Throughput Experimental Data 103
Andrey Y. Sivachenko

6 Integrative Pathway Analysis of Disease Molecular Data 121
Andrej Bugrim, Zoltan Dezso, Yuri Nikolsky, and Tatiana Nikolskaya

7 Whole-Genome Expression Profiling of Papillary Serous Ovarian Cancer: Activated Pathways,Potential Targets, and Noise 149
John Farley, Laurent L. Ozbun, and Michael J. Birrer

8 Mammalian Proteome and Toxicant Network Analysis 165
Sean Ekins and Craig N. Giroux

9 Unraveling Mechanisms of Toxicity with the Power of Pathways: ToxWiz Tool as an IllustrativeExample 195
Mark P. Kühnel, Bojana Cosovic, Goran Medic, Robert B. Russell, and Gordana Apic

10 Impact of Chemistry Information on Pathway Analysis 219
Sreenivas Devidas

11 Propagation of Concentration Perturbations in Equilibrium Protein Binding Networks 237
Sergei Maslov and Iaroslav Ispolatov

12 An Adaptive System Model of the Yeast Glucose Sensor System 263
Todor Vujasinovic and André Siniša Žampera

13 Present and Future of Pathway Analysis in Drug Discovery 285
Anton Yuryev

Index 297

"Pathway analysis will help lead to a better understanding of the chemistry of living systems and the aberrations that disrupt health. This new book will serve as a beacon to research interested in this field." (Journal of Medicinal Chemistry, April 9, 2009) ANTON YURYEV, PhD, is the Senior Director of Application Science at Ariadne Genomics Inc. His department studies the topological and evolutionary properties of biological networks and develops algorithms for pathway reconstruction and analysis of high-throughput data. Dr. Yuryev has published more than thirty scientific publications and is the author of several algorithms for primer design and pathway analysis. Novel computational approaches to improve the effectiveness and efficiency of drug discovery

With chapters contributed by pioneers in the field, Pathway Analysis for Drug Discovery offers readers both important new research findings and state-of-the-science reviews. The book not only presents the latest developments in pathway analysis, it also explains how these developments can improve and accelerate drug discovery, highlighting new opportunities for drug development.

Rather than search for and pore through scores of articles published in disparate sources, readers can turn to Pathway Analysis for Drug Discovery. This single, carefully edited work:

• Introduces drug discovery researchers to novel computational approaches that enable them to better understand molecular function

• Focuses on cell and molecular signaling pathways, demonstrating how the underlying method theory and algorithm details are used in drug discovery

• Offers a comprehensive overview and unbiased assessment of applied methods for the pharmaceutical industry

In addition to traditional computational methods and software for pathway analysis, the book also covers:

• Pathway reconstruction of diseases and toxic states

• Pathway analysis for selection of drug targets, lead compound validation, and prediction of compound ADMET properties

• Dynamic modeling of drug responses

• Pathway analysis for design of selective drug mixtures and promiscuous drugs

Researchers who turn to this book will discover a variety of leading-edge methods to improve both the effectiveness and efficiency of their drug discovery and design efforts and gain an understanding of the role of pathway analysis infrastructure in modern and future drug discovery.