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Series GSE27204 Query DataSets for GSE27204
Status Public on Dec 31, 2015
Title Expression data in HK-2 cells following exposure to Tox 2 compounds: CdCl, Di, and Kbr
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Background: The development of a new drug from candidate to market is a complex process requiring vast resources of time, money and personnel. The rate of failure in the development pipeline is enormous, leading to wasted resources that could have been better employed on alternative candidates. The requirement for early stage prediction of toxicity is, then, of paramount importance to expedite the introduction of new therapies to clinical practice. To date, most transcriptomics efforts to solve this problem have applied Support Vector Machine techniques to data derived from in vivo studies in rats.

Results: We applied a toxicogenomics approach to determine whether known renal toxicants could be identified as such from their effects on the transcriptome of the human renal proximal tubular epithelial cell line, HK-2. Based on clustering of differentially expressed genes, we identified 3 toxicity groups within the set of compounds. We used Random Forest to generate a classifier to accurately place compounds in groups. The classifier is based on a signature biomarker comprising 21 genes identified by Random Forest and could differentiate between the groups with high accuracy. Furthermore, we could correctly classify external samples from a dataset exhibiting a marked ‘batch effect’.

Conclusions: No toxicity-associated gene expression alterations could be identified across a set of toxic compounds. Random Forest is a suitable technique for the classification of compounds into toxicity groups. Using a measure of differential expression rather than expression level per se generates a robust classifier that can potentially be applied in a platform-independent manner.
 
Overall design Gene expression changes in HK-2 cells were measured following exposure to 9 different compounds over a range of doses and time-points with the aim of finding biological signatures of toxicity. Clustering of the resulting gene expression data revealed 3 groups of nephrotoxic compounds (Tox 1, Tox 2 and Tox 3), each exhibiting their own distinct effect on HK-2 cells.

This study measures gene expression changes following exposure to CdCl, Di, Kbr, or control over 12 hrs, 24 hrs, and/or 48 hrs. Three biological replicates per compound/time-point.
 
Contributor(s) Gruber LN, Daha MR, Ryan MP
Citation missing Has this study been published? Please login to update or notify GEO.
Submission date Feb 09, 2011
Last update date Mar 25, 2019
Contact name Peadar O'Gaora
Organization name UCD
Street address Belfield
City Dublin
ZIP/Postal code Dublin 4
Country Ireland
 
Platforms (1)
GPL570 [HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array
Samples (36)
GSM672136 HK-2 cells, CdCl and Di, t12h, control sample, biological rep 1, Tox2
GSM672137 HK-2 cells, CdCl and Di, t12h, control sample, biological rep 2, Tox2
GSM672138 HK-2 cells, CdCl and Di, t12h, control sample, biological rep 3, Tox2
This SubSeries is part of SuperSeries:
GSE27211 Gene expression changes in HK-2 cells following exposure to nephrotoxic compounds
Relations
BioProject PRJNA141987

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE27204_RAW.tar 172.0 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table
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