Monitoring expression of genes involved in drug metabolism and toxicology using DNA microarrays

2001 ◽  
Vol 5 (4) ◽  
pp. 161-170 ◽  
Author(s):  
DAVID GERHOLD ◽  
MEIQING LU ◽  
JIAN XU ◽  
CHRISTOPHER AUSTIN ◽  
C. THOMAS CASKEY ◽  
...  
Keyword(s):  
Gene Expression ◽  
Drug Metabolism ◽  
Stress Responses ◽  
Dna Microarrays ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Metabolic Effects ◽  
Microarray Technology ◽  
Drug Candidates ◽  
Expression Of Genes

Oligonucleotide DNA microarrays were investigated for utility in measuring global expression profiles of drug metabolism genes. This study was performed to investigate the feasibility of using microarray technology to minimize the long, expensive process of testing drug candidates for safety in animals. In an evaluation of hybridization specificity, microarray technology from Affymetrix distinguished genes up to a threshold of ∼90% DNA identity. Oligonucleotides representing human cytochrome P-450 gene CYP3A5 showed heterologous hybridization to CYP3A4 and CYP3A7 RNAs. These genes could be clearly distinguished by selecting a subset of oligonucleotides that hybridized selectively to CYP3A5. Further validation of the technology was performed by measuring gene expression profiles in livers of rats treated with vehicle, 3-methylcholanthrene (3MC), phenobarbital, dexamethasone, or clofibrate and by confirming data for six genes using quantitative RT-PCR. Responses of drug metabolism genes, including CYPs, epoxide hydrolases ( EHs), UDP-glucuronosyl transferases ( UGTs), glutathione sulfotransferases ( GSTs), sulfotransferases ( STs), drug transporter genes, and peroxisomal genes, to these well-studied compounds agreed well with, and extended, published observations. Additional gene regulatory responses were noted that characterize metabolic effects or stress responses to these compounds. Thus microarray technology can provide a facile overview of gene expression responses relevant to drug metabolism and toxicology.

Gene expression profiles of homogentisate-treated Fah−/− Hpd−/−mice using DNA microarrays

2006 ◽  
Vol 89 (3) ◽  
pp. 203-209 ◽  
Author(s):  
Yasuhiko Tanaka ◽  
Kimitoshi Nakamura ◽  
Shirou Matsumoto ◽  
Yoshiko Kimoto ◽  
Akito Tanoue ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Microarrays ◽  
Expression Profiles ◽  
Gene Expression Profiles

Building Gene Networks by Analyzing Gene Expression Profiles

2019 ◽  
pp. 27-44
Author(s):  
Crescenzio Gallo
Keyword(s):  
Gene Expression ◽  
Gene Expression Data ◽  
Gene Networks ◽  
Dna Microarrays ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Gene Expression Profiles ◽  
Expression Data ◽  
Gene Expressions ◽  
Over Time

The possible applications of modeling and simulation in the field of bioinformatics are very extensive, ranging from understanding basic metabolic paths to exploring genetic variability. Experimental results carried out with DNA microarrays allow researchers to measure expression levels for thousands of genes simultaneously, across different conditions and over time. A key step in the analysis of gene expression data is the detection of groups of genes that manifest similar expression patterns. In this chapter, the authors examine various methods for analyzing gene expression data, addressing the important topics of (1) selecting the most differentially expressed genes, (2) grouping them by means of their relationships, and (3) classifying samples based on gene expressions.

scholarly journals Environment and vascular bed origin influence differences in endothelial transcriptional profiles of coronary and iliac arteries

2010 ◽  
Vol 299 (3) ◽  
pp. H837-H846 ◽  
Author(s):  
Kelley A. Burridge ◽  
Morton H. Friedman
Keyword(s):  
Gene Expression ◽  
Cell Biology ◽  
Dna Microarrays ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Local Environment ◽  
Epigenetic Mechanism ◽  
Transcriptional Profiles ◽  
Vascular Bed

Atherosclerotic plaques tend to form in the major arteries at certain predictable locations. As these arteries vary in atherosusceptibility, interarterial differences in endothelial cell biology are of considerable interest. To explore the origin of differences observed between typical atheroprone and atheroresistant arteries, we used DNA microarrays to compare gene expression profiles of harvested porcine coronary (CECs) and iliac artery endothelial cells (IECs) grown in static culture out to passage 4. Fewer differences were observed between the transcriptional profiles of CECs and IECs in culture compared with in vivo, suggesting that most differences observed in vivo were due to distinct environmental cues in the two arteries. One-class significance of microarrays revealed that most in vivo interarterial differences disappeared in culture, as fold differences after passaging were not significant for 85% of genes identified as differentially expressed in vivo at 5% false discovery rate. However, the three homeobox genes, HOXA9, HOXA10, and HOXD3, remained underexpressed in coronary endothelium for all passages by at least nine-, eight-, and twofold, respectively. Continued differential expression, despite removal from the in vivo environment, suggests that primarily heritable or epigenetic mechanism(s) influences transcription of these three genes. Quantitative real-time polymerase chain reaction confirmed expression ratios for seven genes associated with atherogenesis and over- or underexpressed by threefold in CECs relative to IECs. The present study provides evidence that both local environment and vascular bed origin modulate gene expression in arterial endothelium. The transcriptional differences observed here may provide new insights into pathways responsible for coronary artery susceptibility.

Immune- and tumor-intrinsic gene expression profiles of response or resistance to tislelizumab as monotherapy or in combination with chemotherapy in non-small cell lung cancer (NSCLC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15258-e15258
Author(s):  
Jayesh Desai ◽  
Jie Wang ◽  
Qing Zhou ◽  
Jun Zhao ◽  
Sanjeev Deva ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Repair ◽  
Clinical Benefit ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Rank Test ◽  
M2 Macrophage ◽  
Intrinsic Factors ◽  
Expression Of Genes ◽  
Intrinsic Gene

e15258 Background: Tislelizumab, an anti-PD-1 monoclonal antibody, showed clinical benefit for patients (pts) with NSCLC alone (NCT02407990, CTR20160872) and in combination with chemotherapy (NCT03432598). Gene expression profiles (GEP) associated with response and resistance to tislelizumab in these studies were assessed. Methods: The GEP of baseline tumor samples from 59 nonsquamous (NSQ) and 42 squamous (SQ) NSCLC pts treated with tislelizumab monotherapy (mono) as ≥1L treatment, and 16 NSQ and 21 SQ pts treated with tislelizumab plus chemotherapy (combo) as 1L treatment were assessed using the 1392-gene HTG GEP EdgeSeq panel. NSQ and SQ cohorts were analyzed separately due to distinct GEP features shown by PCA and t-SNE clustering. Results: Tislelizumab mono and combo showed antitumor activity in NSCLC (Table). In 80 biomarker-evaluable samples, inflamed tumor signatures (inflammatory GEP; antigen presentation GEP) were associated with longer overall survival (log-rank test, NSQ mono: P=0.04, 0.003; NSQ combo: P=0.05, 0.02; SQ combo: P=0.06, 0.06). Monotherapy non-responders (NRs) were clustered into 2 subgroups (NR1, NR2) with distinct GEPs. Compared with responders, NR1 had proliferation signatures (elevated cell cycle [CC] and DNA repair) in both NSQ ( P=0.2, 0.02) and SQ ( P=0.03, 0.4) cohorts, trending toward low inflamed tumor signatures. In NR pts receiving combo, CC and DNA repair signatures were not enriched, and high CC and DNA repair scores were observed in some SQ combo responders versus NRs ( P=0.2, 0.02). NR2 had higher M2 macrophage and Treg cell signatures versus responders in both NSQ and SQ mono, despite high inflamed tumor and low proliferation signatures. NR2 also had increased expression of genes related to immune regulation and angiogenesis, including PIK3CD, CCR2, CD244, IRAK3, and MAP4K1 ( P<0.05) in NSQ, and PIK3CD, CCR2, CD40, CD163, MMP12, VEGFC, and TEK ( P<0.05) in SQ. Conclusions: Clinical benefit in pts with NSCLC receiving tislelizumab (mono or combo) was associated with high inflamed tumor signatures, while elevated immune suppressive cell signatures may indicate resistance. High proliferation signatures were associated with resistance to monotherapy, but not to combination therapy. Both immune- and tumor-intrinsic factors may be considered for validation in future clinical trials. [Table: see text]

Compendium of gene expression profiles comprising a baseline model of the human liver drug metabolism transcriptome

Xenobiotica ◽  
2006 ◽  
Vol 36 (10-11) ◽  
pp. 938-962 ◽  
Author(s):  
J. G. Slatter ◽  
I. E. Templeton ◽  
J. C. Castle ◽  
A. Kulkarni ◽  
T. H. Rushmore ◽  
...  
Keyword(s):  
Gene Expression ◽  
Drug Metabolism ◽  
Human Liver ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Baseline Model

DNA microarrays to study gene expression profiles in testis of fertile and infertile men.

2001 ◽  
Vol 76 (3) ◽  
pp. S40 ◽  
Author(s):  
P Patrizio ◽  
N Hecht ◽  
J Rockett ◽  
J Schmid ◽  
D Dix
Keyword(s):  
Gene Expression ◽  
Dna Microarrays ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Infertile Men ◽  
Study Gene Expression

Analysis of organic solvent tolerance in Escherichia coli using gene expression profiles from DNA microarrays

2003 ◽  
Vol 95 (4) ◽  
pp. 379-383 ◽  
Author(s):  
Shuhei Hayashi ◽  
Rikizo Aono ◽  
Taizo Hanai ◽  
Hirotada Mori ◽  
Takeshi Kobayashi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Escherichia Coli ◽  
Organic Solvent ◽  
Dna Microarrays ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Solvent Tolerance ◽  
Organic Solvent Tolerance
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