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Int J Mol Sci. 2019 Jan 17;20(2). pii: E386. doi: 10.3390/ijms20020386.

Network-Based Assessment of Adverse Drug Reaction Risk in Polypharmacy Using High-Throughput Screening Data.

Author information

1
Computational Genomics Division, National Institute of Genomic Medicine (INMEGEN), Alcaldía de Tlalpan, Ciudad de México C.P. 14610, Mexico. gdeanda@inmegen.edu.mx.
2
Department of Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND 58202, USA. kai.guo@med.und.edu.
3
Department of Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND 58202, USA. junguk.hur@med.und.edu.

Abstract

The risk of adverse drug reactions increases in a polypharmacology setting. High-throughput drug screening with transcriptomics applied to human cells has shown that drugs have effects on several molecular pathways, and these affected pathways may be predictive proxy for adverse drug reactions. Depending on the way that different drugs may contribute to adverse drug reactions, different options may exist in the clinical setting. Here, we formulate a network framework to integrate the relationships between drugs, biological functions, and adverse drug reactions based on the high-throughput drug perturbation data from the Library of Integrated Network-Based Cellular Signatures (LINCS) project. We present network-based parameters that indicate whether a given reaction may be related to the effect of a single drug or to the combination of several drugs, as well as the relative risk of adverse drug reaction manifestation given a certain drug combination.

KEYWORDS:

L1000 assay; LINCS; Library of Integrated Network-Based Cellular Signatures; adverse drug reaction; network pharmacology; polypharmacology; polypharmacy; risk prediction

PMID:
30658437
PMCID:
PMC6358820
DOI:
10.3390/ijms20020386
[Indexed for MEDLINE]
Free PMC Article

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