scholarly journals Enhanced identification and biological validation of differential gene expression via Illumina whole-genome expression arrays through the use of the model-based background correction methodology

2008 ◽  
Vol 36 (10) ◽  
pp. e58-e58 ◽  
Author(s):  
Liang-Hao Ding ◽  
Yang Xie ◽  
Seongmi Park ◽  
Guanghua Xiao ◽  
Michael D. Story
Keyword(s):  
Gene Expression ◽  
Differential Gene Expression ◽  
Background Correction ◽  
Whole Genome ◽  
Expression Arrays ◽  
Biological Validation ◽  
Model Based ◽  
Genome Expression ◽  
Differential Gene ◽  
Whole Genome Expression

Whole genome expression as a quantitative trait

2009 ◽  
Vol 37 (6) ◽  
pp. 1276-1277 ◽  
Author(s):  
John Hardy ◽  
Danyah Trabzuni ◽  
Mina Ryten
Keyword(s):  
Gene Expression ◽  
Genetic Variability ◽  
Disease Risk ◽  
Neurological Diseases ◽  
Whole Genome ◽  
Genome Expression ◽  
Genome Analyses ◽  
Whole Genome Expression ◽  
Influence Gene Expression ◽  
Gene Expression Levels

Surprisingly, whole genome analyses of complex human neurological and psychiatric disorders have revealed that many genetic risk factors are likely to influence gene expression rather than alter protein sequences. Previous analyses of neurological diseases have shown that genetic variability in gene expression levels of deposited proteins influence disease risk. With this background, we have embarked on a comprehensive project to determine the effects of common genetic variability on whole genome gene expression.

Genetic Profiling of Orbital Fibroblasts from Patients with Graves’ Orbitopathy

2021 ◽  
Author(s):  
Giovanna Rotondo Dottore ◽  
Ilaria Bucci ◽  
Giulia Lanzolla ◽  
Iacopo Dallan ◽  
Angela Sframeli ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Cell Proliferation ◽  
Differential Gene Expression ◽  
Global Dna Methylation ◽  
Whole Genome ◽  
Graves Orbitopathy ◽  
Differential Gene ◽  
And Control ◽  
Orbital Fibroblasts

Abstract Context Graves’ orbitopathy (GO) is an autoimmune disease that persists when immunosuppression is achieved. Orbital fibroblasts from GO patients display peculiar phenotypes even if not exposed to autoimmunity, possibly reflecting genetic or epigenetic mechanisms, which we investigated here. Objective We aimed to explore potential genetic or epigenetic differences using primary cultures of orbital fibroblasts from GO and control patients. Methods Cell proliferation, hyaluronic acid (HA) secretion, and HA synthases (HAS) were measured. Next-generation sequencing and gene expression analysis of the whole genome were performed, as well as real-time-PCR of selected genes and global DNA methylation assay on orbital fibroblasts from 6 patients with GO and 6 control patients from a referral center. Results Cell proliferation was higher in GO than in control fibroblasts. Likewise, HA in the cell medium was higher in GO fibroblasts. HAS-1 and HAS-2 did not differ between GO and control fibroblasts, whereas HAS-3 was more expressed in GO fibroblasts. No relevant gene variants were detected by whole-genome sequencing. However, 58 genes were found to be differentially expressed in GO compared with control fibroblasts, and RT-PCR confirmed the findings in 10 selected genes. We postulated that the differential gene expression was related to an epigenetic mechanism, reflecting diverse DNA methylation, which we therefore measured. In support of our hypothesis, global DNA methylation was significantly higher in GO fibroblasts. Conclusions We propose that, following an autoimmune insult, DNA methylation elicits differential gene expression and sustains the maintenance of GO.

scholarly journals Temporal genomewide expression profiling of DSS colitis reveals novel inflammatory and angiogenesis genes similar to ulcerative colitis

2011 ◽  
Vol 43 (1) ◽  
pp. 43-56 ◽  
Author(s):  
Kai Fang ◽  
Megan Bruce ◽  
Christopher B. Pattillo ◽  
Songlin Zhang ◽  
Randolph Stone ◽  
...  
Keyword(s):  
Gene Expression ◽  
Ulcerative Colitis ◽  
Expression Profiling ◽  
Profile Analysis ◽  
Whole Genome ◽  
Qrt Pcr ◽  
Dss Colitis ◽  
Genome Expression ◽  
Expression Profile Analysis ◽  
Whole Genome Expression

Dextran sodium sulfate (DSS)-induced colitis is widely used to study pathological mechanisms and potential treatments of inflammatory bowel disease. Because temporal changes in genome expression profiles remain unknown in this model, we performed whole genome expression profile analysis during the development of DSS colitis in comparison with ulcerative colitis (UC) specimens to identify novel and common responses during disease. Colon tissue from DSS-treated mice was collected at days 0, 2, 4, and 6. Half of each specimen was used for histopathological analysis and half for Affymetrix whole genome expression profiling and qRT-PCR validation. Genesifter and Ingenuity software analysis was used to identify differentially expressed genes and perform interactive network analysis. Identified DSS-associated genes in mice were also compared with UC patient data. We identified 1,609 genes that were significantly altered during DSS colitis; the majority were functionally related to inflammation, angiogenesis, metabolism, biological adhesion, cellular growth and proliferation, and cell-to-cell signaling responses. Five hundred and one genes were progressively upregulated, while one hundred seventy-three genes were progressively downregulated. Changes in gene expression were validated in a subset of 33 genes by qRT-PCR, with r2 = 0.925. Ingenuity gene interaction network analysis revealed novel relationships among antigen presentation, cell morphology, and other biological functions in the DSS mouse. Finally, DSS colitis gene array data were compared with UC patient array data: 152 genes were similarly upregulated, and 22 genes were downregulated. Temporal genomewide expression profile analysis of DSS-induced colitis revealed novel associations with various immune responses and tissue remodeling events such as angiogenesis similar to those in UC patients. This study provides a comprehensive view of DSS colitis changes in colon gene expression and identifies common molecules with clinical specimens that are interesting targets for further investigation.

scholarly journals Alternative splicing and differential gene expression in colon cancer detected by a whole genome exon array

BMC Genomics ◽  
2006 ◽  
Vol 7 (1) ◽  
Author(s):  
Paul J Gardina ◽  
Tyson A Clark ◽  
Brian Shimada ◽  
Michelle K Staples ◽  
Qing Yang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colon Cancer ◽  
Alternative Splicing ◽  
Differential Gene Expression ◽  
Exon Array ◽  
Whole Genome ◽  
Differential Gene

scholarly journals Sum1 and Ndt80 Proteins Compete for Binding to Middle Sporulation Element Sequences That Control Meiotic Gene Expression

2003 ◽  
Vol 23 (14) ◽  
pp. 4814-4825 ◽  
Author(s):  
Michael Pierce ◽  
Kirsten R. Benjamin ◽  
Sherwin P. Montano ◽  
Millie M. Georgiadis ◽  
Edward Winter ◽  
...  
Keyword(s):  
Gene Expression ◽  
Saccharomyces Cerevisiae ◽  
Dna Sequence ◽  
Whole Genome ◽  
Sequence Element ◽  
Genome Expression ◽  
Distinct Sequence ◽  
Whole Genome Expression ◽  
Sequence Requirements ◽  
Sporulation Genes

ABSTRACT A key transition in meiosis is the exit from prophase and entry into the nuclear divisions, which in the yeast Saccharomyces cerevisiae depends upon induction of the middle sporulation genes. Ndt80 is the primary transcriptional activator of the middle sporulation genes and binds to a DNA sequence element termed the middle sporulation element (MSE). Sum1 is a transcriptional repressor that binds to MSEs and represses middle sporulation genes during mitosis and early sporulation. We demonstrate that Sum1 and Ndt80 have overlapping yet distinct sequence requirements for binding to and acting at variant MSEs. Whole-genome expression analysis identified a subset of middle sporulation genes that was derepressed in a sum1 mutant. A comparison of the MSEs in the Sum1-repressible promoters and MSEs from other middle sporulation genes revealed that there are distinct classes of MSEs. We show that Sum1 and Ndt80 compete for binding to MSEs and that small changes in the sequence of an MSE can yield large differences in which protein is bound. Our results provide a mechanism for differentially regulating the expression of middle sporulation genes through the competition between the Sum1 repressor and the Ndt80 activator.

scholarly journals Multiplicative background correction for spotted microarrays to improve reproducibility

2006 ◽  
Vol 87 (3) ◽  
pp. 195-206 ◽  
Author(s):  
DABAO ZHANG ◽  
MIN ZHANG ◽  
MARTIN T. WELLS
Keyword(s):  
Gene Expression ◽  
Data Analysis ◽  
Differential Gene Expression ◽  
Microarray Data ◽  
Background Noise ◽  
Simple Approach ◽  
Background Correction ◽  
Microarray Data Analysis ◽  
Differential Gene ◽  
Gene Expression Levels

We propose a simple approach, the multiplicative background correction, to solve a perplexing problem in spotted microarray data analysis: correcting the foreground intensities for the background noise, especially for spots with genes that are weakly expressed or not at all. The conventional approach, the additive background correction, directly subtracts the background intensities from foreground intensities. When the foreground intensities marginally dominate the background intensities, the additive background correction provides unreliable estimates of the differential gene expression levels and usually presents M–A plots with ‘fishtails’ or fans. Unreliable additive background correction makes it preferable to ignore the background noise, which may increase the number of false positives. Based on the more realistic multiplicative assumption instead of the conventional additive assumption, we propose to logarithmically transform the intensity readings before the background correction, with the logarithmic transformation symmetrizing the skewed intensity readings. This approach not only precludes the ‘fishtails’ and fans in the M–A plots, but provides highly reproducible background-corrected intensities for both strongly and weakly expressed genes. The superiority of the multiplicative background correction to the additive one as well as the no background correction is justified by publicly available self-hybridization datasets.

A computational analysis of whole-genome expression data reveals chromosomal domains of gene expression

10.1038/79896 ◽  
2000 ◽  
Vol 26 (2) ◽  
pp. 183-186 ◽  
Author(s):  
Barak A. Cohen ◽  
Robi D. Mitra ◽  
Jason D. Hughes ◽  
George M. Church
Keyword(s):  
Gene Expression ◽  
Computational Analysis ◽  
Whole Genome ◽  
Expression Data ◽  
Genome Expression ◽  
Whole Genome Expression

Gene expression profiling of prostate tissue based on variable expression of 5-alpha reductase 2.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 143-143
Author(s):  
Keyan Salari ◽  
Seth Bechis ◽  
Rongbin Ge ◽  
Jian Hong ◽  
Aleksander Otsetov ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hierarchical Clustering ◽  
Promoter Methylation ◽  
Expression Profiling ◽  
Molecular Subtypes ◽  
Prostatic Tissue ◽  
Whole Genome ◽  
Variable Expression ◽  
Genome Expression ◽  
Whole Genome Expression

143 Background: Androgen signaling plays a central role in the pathophysiology of both benign and malignant prostatic disease. We previously showed that some men carry epigenetic modifications of the 5-alpha reductase (AR) promoter that modulate gene expression, raising the hypothesis that there may be molecular heterogeneity underlying the variability in clinical response to 5-AR inhibitors for management of benign and malignant prostatic diseases. In this study, we performed whole-genome expression profiling of prostatic tissue based on variable expression of 5-AR2 to determine whether molecular subtypes of clinical relevance could be identified. Methods: Prostatic tissue specimens were obtained from 22 patients with symptomatic BPH undergoing prostate debulking surgery. 5-AR2 protein expression was measured by immunohistochemistry, and 5-AR2 promoter methylation determined by PCR. RNA was extracted from each specimen and whole-genome expression profiling was performed using Illumina Human BeadChip Arrays. Gene expression data was analyzed by unsupervised hierarchical clustering and Gene Set Enrichment Analysis. Results: Unsupervised hierarchical clustering identified two subtypes of patients with distinct gene expression signatures. Among the most differentially expressed genes were several notable androgen-regulated genes, including TMPRSS2, NKX3-1, AZGP1, KLK3 (encoding the PSA protein) and multiple other members of the kallikrein family of serine proteases (all P< 0.001, FDR < 0.02). Multiple gene sets composed of androgen-regulated genes and androgen receptor target genes were found to be significantly enriched in one of the two subtypes. Interestingly, patients from this Androgen-Up subtype were also noted to have a higher frequency of 5-AR2 promoter methylation (though not statistically significant). Conclusions: Our findings suggest that there are distinct molecular subtypes among prostatic tissues with variable expression of 5-AR2, driven by differences in androgen gene regulation. These differences may partially explain the variable response to 5-AR inhibitors and thereby inform clinical strategies for devising therapies for benign and malignant prostatic disease.

scholarly journals Use of Routinely Collected Amniotic Fluid for Whole-Genome Expression Analysis of Polygenic Disorders

2006 ◽  
Vol 52 (11) ◽  
pp. 2013-2020 ◽  
Author(s):  
Gyula Richárd Nagy ◽  
Balázs Gyõrffy ◽  
Orsolya Galamb ◽  
Béla Molnár ◽  
Bálint Nagy ◽  
...  
Keyword(s):  
Gene Expression ◽  
Amniotic Fluid ◽  
Pregnant Women ◽  
Differential Gene Expression ◽  
Neural Tube ◽  
Neural Tube Defects ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Whole Genome ◽  
Differential Gene

Abstract Background: Neural tube defects related to polygenic disorders are the second most common birth defects in the world, but no molecular biologic tests are available to analyze the genes involved in the pathomechanism of these disorders. We explored the use of routinely collected amniotic fluid to characterize the differential gene expression profiles of polygenic disorders. Methods: We used oligonucleotide microarrays to analyze amniotic fluid samples obtained from pregnant women carrying fetuses with neural tube defects diagnosed during ultrasound examination. The control samples were obtained from pregnant women who underwent routine genetic amniocentesis because of advanced maternal age (&gt;35 years). We also investigated specific folate-related genes because maternal periconceptional folic acid supplementation has been found to have a protective effect with respect to neural tube defects. Results: Fetal mRNA from amniocytes was successfully isolated, amplified, labeled, and hybridized to whole-genome transcript arrays. We detected differential gene expression profiles between cases and controls. Highlighted genes such as SLA, LST1, and BENE might be important in the development of neural tube defects. None of the specific folate-related genes were in the top 100 associated transcripts. Conclusions: This pilot study demonstrated that a routinely collected amount of amniotic fluid (as small as 6 mL) can provide sufficient RNA to successfully hybridize to expression arrays. Analysis of the differences in fetal gene expressions might help us decipher the complex genetic background of polygenic disorders.

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