An Integrative Computational Approach for a Prioritization of Key Transcription Regulators Associated With Nanomaterial-Induced Toxicity

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Title: An Integrative Computational Approach for a Prioritization of Key Transcription Regulators Associated With Nanomaterial-Induced Toxicity
Authors: Zhernovkov, VadimSantra, TapeshCassidy, HilaryRukhlenko, Oleksii S.Matallanas, DavidKrstic, AleksandarKolch, WalterLobaskin, VladimirKholodenko, Boris N.
Permanent link: http://hdl.handle.net/10197/11108
Date: Oct-2019
Online since: 2019-10-04T13:45:25Z
Abstract: A rapid increase of new nanomaterial products poses new challenges for their risk assessment. Current traditional methods for estimating potential adverse health effect of nanomaterials (NMs) are complex, time consuming and expensive. In order to develop new prediction tests for nanotoxicity evaluation, a systems biology approach and data from high-throughput omics experiments can be used. We present a computational approach that combines reverse engineering techniques, network analysis and pathway enrichment analysis for inferring the transcriptional regulation landscape and its functional interpretation. To illustrate this approach, we used published transcriptomic data derived from mice lung tissue exposed to carbon nanotubes (NM-401 and NRCWE-26). Because fibrosis is the most common adverse effect of these NMs, we included in our analysis the data for bleomycin (BLM) treatment, which is a well-known fibrosis inducer. We inferred gene regulatory networks for each NM and BLM to capture functional hierarchical regulatory structures between genes and their regulators. Despite the different nature of the lung injury caused by nanoparticles and BLM, we identified several conserved core regulators for all agents. We reason that these regulators can be considered as early predictors of toxic responses after NMs exposure. This integrative approach, which refines traditional methods of transcriptomic analysis, can be useful for prioritization of potential core regulators and generation of new hypothesis about mechanisms of nanoparticles toxicity.
Funding Details: European Commission Horizon 2020
metadata.dc.description.othersponsorship: NanoCommons
Type of material: Journal Article
Publisher: Oxford University Press
Journal: Toxicological sciences
Volume: 171
Issue: 2
Start page: 303
End page: 314
Copyright (published version): 2019 the Authors
Keywords: BleomycinCarbon nanotubesFibrosisGene regulationGene regulatory networkNanoparticles
DOI: 10.1093/toxsci/kfz151
Language: en
Status of Item: Peer reviewed
Appears in Collections:Conway Institute Research Collection
Physics Research Collection
SBI Research Collection
Medicine Research Collection

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