Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Yu H

PROVIDER: S-EPMC5548804 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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

Yu Hasun H Jung Jinmyung J Yoon Seyeol S Kwon Mijin M Bae Sunghwa S Yim Soorin S Lee Jaehyun J Kim Seunghyun S Kang Yeeok Y Lee Doheon D

Scientific reports 20170808 1

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 ...[more]

PMID: 28790372

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Project description:BackgroundComputational analysis of complex diseases involving multiple organs requires the integration of multiple different models into a unified model. Different models are often constructed in heterogeneous formats. Thus, the integration of the models requires a standard language format that can effectively represent essential biological information. However, the previously introduced formats have limitations that prevent from adequately representing essential biological information, particularly specifications of bio-molecules and biological contexts.ResultsWe defined an XML-based markup language called context-oriented directed association markup language (CODA-ML), which better represents essential biological information. The CODA-ML has two major strengths in designating molecular specifications and biological contexts. It can cover heterogeneous entity types involved in biological events (e.g. gene/protein, compound, cellular function, disease). Molecular types of entities can have molecular specifications which include detailed information of a molecule from isoforms to modifications, enabling high-resolution representation of molecules. In addition, it can distinguish biological events that vary depending on different biological contexts such as cell types or disease conditions. Especially representation of inter-cellular events as well as intra-cellular events is available. These two major strengths can resolve contradictory associations when different models are integrated into one unified model, which improves the accuracy of the model.ConclusionsWith the CODA-ML, diverse models such as signaling pathways, metabolic pathways, and gene regulatory pathways can be represented in a unified language format. Heterogeneous entity types can be covered by the CODA-ML, thus it enables detailed description for the mechanisms of diseases or drugs from multiple perspectives (e.g., molecule, function or disease). The CODA-ML is expected to help integrate different models into one systemic model in an efficient and effective. The unified model can be used to perform computational analysis not only for cancer but also for other complex diseases involving multiple organs beyond a single cell.

Project description:BackgroundIndividualized drug response prediction is vital for achieving personalized treatment of cancer and moving precision medicine forward. Large-scale multi-omics profiles provide unprecedented opportunities for precision cancer therapy.MethodsIn this study, we propose a pipeline to identify subpathway signatures for anticancer drug response of individuals by integrating the comprehensive contributions of multiple genetic and epigenetic (gene expression, copy number variation and DNA methylation) alterations.ResultsTotally, 46 subpathway signatures associated with individual responses to different anticancer drugs were identified based on five cancer-drug response datasets. We have validated the reliability of subpathway signatures in two independent datasets. Furthermore, we also demonstrated these multi-omics subpathway signatures could significantly improve the performance of anticancer drug response prediction. In-depth analysis of these 46 subpathway signatures uncovered the essential roles of three omics types and the functional associations underlying different anticancer drug responses. Patient stratification based on subpathway signatures involved in anticancer drug response identified subtypes with different clinical outcomes, implying their potential roles as prognostic biomarkers. In addition, a landscape of subpathways associated with cellular responses to 191 anticancer drugs from CellMiner was provided and the mechanism similarity of drug action was accurately unclosed based on these subpathways. Finally, we constructed a user-friendly web interface-CancerDAP ( http://bio-bigdata.hrbmu.edu.cn/CancerDAP/ ) available to explore 2751 subpathways relevant with 191 anticancer drugs response.ConclusionsTaken together, our study identified and systematically characterized subpathway signatures for individualized anticancer drug response prediction, which may promote the precise treatment of cancer and the study for molecular mechanisms of drug actions.

Dataset Information

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

Publications

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

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