Journal Article

CODA: Integrating multi-level context-oriented directed associations for analysis of drug effects

Yoon, Seyeol, Lee, Jaehyun, Kang, Yeeok, Yu, Hasun, Yim, Soorin, Lee, Doheon, Kwon, Mijin, Kim, Seunghyun, Jung, Jinmyung, Bae, Sunghwa

2017

Overview

In silico network-based methods have shown promising results in the field of drug development. Yet, most of networks used in the previous research have not included context information even though biological associations actually do appear in the specific contexts. Here, we reconstruct an anatomical context-specific network by assigning contexts to biological associations using protein expression data and scientific literature. Furthermore, we employ the context-specific network for the analysis of drug effects with a proximity measure between drug targets and diseases. Distinct from previous context-specific networks, intercellular associations and phenomic level entities such as biological processes are included in our network to represent the human body. It is observed that performances in inferring drug-disease associations are increased by adding context information and phenomic level entities. In particular, hypertension, a disease related to multiple organs and associated with several phenomic level entities, is analyzed in detail to investigate how our network facilitates the inference of drug-disease associations. Our results indicate that the inclusion of context information, intercellular associations, and phenomic level entities can contribute towards a better prediction of drug-disease associations and provide detailed insight into understanding of how drugs affect diseases in the human body.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 631/114/2391 / 631/114/2401 / 631/154/1435/2418 / Algorithms / Brain - drug effects / Brain - metabolism / Brain - pathology / Cardiovascular Diseases - drug therapy / Cardiovascular Diseases - genetics / Cardiovascular Diseases - metabolism / Cardiovascular Diseases - pathology / Computational Biology - methods / Connective Tissue Diseases - drug therapy / Connective Tissue Diseases - genetics / Connective Tissue Diseases - metabolism / Connective Tissue Diseases - pathology / Digestive System Diseases - drug therapy / Digestive System Diseases - genetics / Digestive System Diseases - metabolism / Digestive System Diseases - pathology / Disease / Drug development / Drugs, Investigational - pharmacokinetics / Genes / Genomics / Hematologic Diseases - drug therapy / Hematologic Diseases - genetics / Hematologic Diseases - metabolism / Hematologic Diseases - pathology / Human body / Humanities and Social Sciences / Humans / Hypertension / Kidney - drug effects / Kidney - metabolism / Kidney - pathology / Liver - drug effects / Liver - metabolism / Liver - pathology / Lung - drug effects / Lung - metabolism / Lung - pathology / Metabolic Diseases - drug therapy / Metabolic Diseases - genetics / Metabolic Diseases - metabolism / Metabolic Diseases - pathology / Metabolism / multidisciplinary / Muscle, Skeletal - drug effects / Muscle, Skeletal - metabolism / Muscle, Skeletal - pathology / Musculoskeletal Diseases - drug therapy / Musculoskeletal Diseases - genetics / Musculoskeletal Diseases - metabolism / Musculoskeletal Diseases - pathology / Myocardium - metabolism / Myocardium - pathology / Neoplasms - drug therapy / Neoplasms - genetics / Neoplasms - metabolism / Neoplasms - pathology / Nervous System Diseases - drug therapy / Nervous System Diseases - genetics / Nervous System Diseases - metabolism / Nervous System Diseases - pathology / Nutrition Disorders - drug therapy / Nutrition Disorders - genetics / Nutrition Disorders - metabolism / Nutrition Disorders - pathology / Ontology / Organ Specificity / Prescription Drugs - pharmacokinetics / Protein expression / Proteins / Respiratory Tract Diseases - drug therapy / Respiratory Tract Diseases - genetics / Respiratory Tract Diseases - metabolism / Respiratory Tract Diseases - pathology / Science / Science (multidisciplinary) / Skin - drug effects / Skin - metabolism / Skin - pathology