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Inferring protein domains associated with drug side effects based on drug-target interaction network.

ABSTRACT: BACKGROUND: Most phenotypic effects of drugs are involved in the interactions between drugs and their target proteins, however, our knowledge about the molecular mechanism of the drug-target interactions is very limited. One of challenging issues in recent pharmaceutical science is to identify the underlying molecular features which govern drug-target interactions. RESULTS: In this paper, we make a systematic analysis of the correlation between drug side effects and protein domains, which we call "pharmacogenomic features," based on the drug-target interaction network. We detect drug side effects and protein domains that appear jointly in known drug-target interactions, which is made possible by using classifiers with sparse models. It is shown that the inferred pharmacogenomic features can be used for predicting potential drug-target interactions. We also discuss advantages and limitations of the pharmacogenomic features, compared with the chemogenomic features that are the associations between drug chemical substructures and protein domains. CONCLUSION: The inferred side effect-domain association network is expected to be useful for estimating common drug side effects for different protein families and characteristic drug side effects for specific protein domains.

SUBMITTER: Iwata H

PROVIDER: S-EPMC4029543 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Inferring protein domains associated with drug side effects based on drug-target interaction network.

Iwata Hiroaki H Mizutani Sayaka S Tabei Yasuo Y Kotera Masaaki M Goto Susumu S Yamanishi Yoshihiro Y

BMC systems biology 20131213

<h4>Background</h4>Most phenotypic effects of drugs are involved in the interactions between drugs and their target proteins, however, our knowledge about the molecular mechanism of the drug-target interactions is very limited. One of challenging issues in recent pharmaceutical science is to identify the underlying molecular features which govern drug-target interactions.<h4>Results</h4>In this paper, we make a systematic analysis of the correlation between drug side effects and protein domains, ...[more]

PMID: 24565527

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Project description:Although there are many studies of drugs and their side effects, the underlying mechanisms of these side effects are not well understood. It is also difficult to understand the specific pathways between drugs and side effects. The present study seeks to construct putative paths between drugs and their side effects by applying text-mining techniques to free text of biomedical studies, and to develop ranking metrics that could identify the most-likely paths. We extracted three types of relationships-drug-protein, protein-protein, and protein⁻side effect-from biomedical texts by using text mining and predefined relation-extraction rules. Based on the extracted relationships, we constructed whole drug-protein⁻side effect paths. For each path, we calculated its ranking score by a new ranking function that combines corpus- and ontology-based semantic similarity as well as co-occurrence frequency. We extracted 13 plausible biomedical paths connecting drugs and their side effects from cancer-related abstracts in the PubMed database. The top 20 paths were examined, and the proposed ranking function outperformed the other methods tested, including co-occurrence, COALS, and UMLS by P@5-P@20. In addition, we confirmed that the paths are novel hypotheses that are worth investigating further. The risk of side effects has been an important issue for the US Food and Drug Administration (FDA). However, the causes and mechanisms of such side effects have not been fully elucidated. This study extends previous research on understanding drug side effects by using various techniques such as Named Entity Recognition (NER), Relation Extraction (RE), and semantic similarity. It is not easy to reveal the biomedical mechanisms of side effects due to a huge number of possible paths. However, we automatically generated predictable paths using the proposed approach, which could provide meaningful information to biomedical researchers to generate plausible hypotheses for the understanding of such mechanisms.

Dataset Information

Inferring protein domains associated with drug side effects based on drug-target interaction network.

Publications

Inferring protein domains associated with drug side effects based on drug-target interaction network.

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