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| Status |
Public on Dec 31, 2015 |
| Title |
Expression data in HK-2 cells following exposure to Aa_hd |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| 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.
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| 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 a high dose of Aa or a control over 24 hrs or 48 hrs. Three biological replicates per compound/time-point.
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| Contributor(s) |
Gruber LN, Daha MR, Ryan MP |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
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| Submission date |
Feb 08, 2011 |
| Last update date |
Mar 25, 2019 |
| Contact name |
Peadar O'Gaora |
| Organization name |
UCD
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| Street address |
Belfield
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| City |
Dublin |
| ZIP/Postal code |
Dublin 4 |
| Country |
Ireland |
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| Platforms (1) |
| GPL570 |
[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array |
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| Samples (12)
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| GSM671534 |
HK-2 cells, Aa, hd, t24h, biological rep 1 |
| GSM671535 |
HK-2 cells, Aa, hd, t24h, biological rep 2 |
| GSM671536 |
HK-2 cells, Aa, hd, t24h, biological rep 3 |
| GSM671537 |
HK-2 cells, Aa, hd, t48h, biological rep 1 |
| GSM671538 |
HK-2 cells, Aa, hd, t48h, biological rep 2 |
| GSM671539 |
HK-2 cells, Aa, hd, t48h, biological rep 3 |
| GSM671540 |
HK-2 cells, Aa, hd, t24h, control sample, biological rep 1 |
| GSM671541 |
HK-2 cells, Aa, hd, t24h, control sample, biological rep 2 |
| GSM671542 |
HK-2 cells, Aa, hd, t24h, control sample, biological rep 3 |
| GSM671543 |
HK-2 cells, Aa, hd, t48h, control sample, biological rep 1 |
| GSM671544 |
HK-2 cells, Aa, hd, t48h, control sample, biological rep 2 |
| GSM671545 |
HK-2 cells, Aa, hd, t48h, control sample, biological rep 3 |
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| This SubSeries is part of SuperSeries: |
| GSE27211 |
Gene expression changes in HK-2 cells following exposure to nephrotoxic compounds |
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| Relations |
| BioProject |
PRJNA142081 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE27168_RAW.tar |
59.6 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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