scholarly journals The Colon Transcriptome Explorer (CoTrEx) 2.0: a Reference Web-Based Resource for Exploring Population-Based Normal Colon Gene Expression

2021 ◽  
Author(s):  
Virginia Díez-Obrero ◽  
Ferran Moratalla-Navarro ◽  
Christopher Dampier ◽  
Matthew Devall ◽  
Robert Carreras-Torres ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prediction Models ◽  
Expression Profiles ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Normal Colon ◽  
Colon Tissue ◽  
Web Based ◽  
Normal Colon Tissue ◽  
High Interest

Gene expression data is key for the functional annotation of single nucleotide polymorphisms (SNPs) identified in genome-wide association studies (GWAS). Expression and splicing quantitative trait loci (e/sQTLs) in normal colon tissue, such as those from the University of Barcelona and University of Virginia RNA sequencing project (BarcUVa-Seq) and the Genotype-Tissue Expression project (GTEx), are required to gain biological insight of colon-related diseases risk loci. Moreover, transcriptome-wide association studies (TWAS) rely on reference gene expression imputation panels in the tissue of interest to nominate susceptibility genes. Also, it is of high interest to study the relationships between genes in a network framework. For facilitating these analyses, we have updated and expanded the scope of the Colon Transcriptome Explorer (CoTrEx) to the version 2.0. This web-based resource provides exhaustive visualization and analysis of transcriptome-wide gene expression profiles of normal colon tissue from BarcUVa-Seq and GTEx. In addition to the integration of new datasets, CoTrEx 2.0 provides additional e/sQTLs sets, as well as gene expression prediction models and regulatory and co-expression networks. It is freely available at https://barcuvaseq.org/cotrex/. Overall, it is of high interest for researchers aiming to investigate the genetic susceptibility to colon-related complex traits and diseases.

scholarly journals Genotype-Based Gene Expression in Colon Tissue—Prediction Accuracy and Relationship with the Prognosis of Colorectal Cancer Patients

2020 ◽  
Vol 21 (21) ◽  
pp. 8150
Author(s):  
Heike Deutelmoser ◽  
Justo Lorenzo Bermejo ◽  
Axel Benner ◽  
Korbinian Weigl ◽  
Hanla A. Park ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Prediction Accuracy ◽  
Inverse Association ◽  
Normal Colon ◽  
Colon Tissue ◽  
Normal Colon Tissue ◽  
Study Population ◽  
The Uk ◽  
Colorectal Cancer Patients

Colorectal cancer (CRC) survival has environmental and inherited components. The expression of specific genes can be inferred based on individual genotypes—so called expression quantitative trait loci. In this study, we used the PrediXcan method to predict gene expression in normal colon tissue using individual genotype data from 91 CRC patients and examined the correlation ρ between predicted and measured gene expression levels. Out of 5434 predicted genes, 58% showed a negative ρ value and only 16% presented a ρ higher than 0.10. We subsequently investigated the association between genotype-based gene expression in colon tissue for genes with ρ > 0.10 and survival of 4436 CRC patients. We identified an inverse association between the predicted expression of ARID3B and CRC-specific survival for patients with a body mass index greater than or equal to 30 kg/m2 (HR (hazard ratio) = 0.66 for an expression higher vs. lower than the median, p = 0.005). This association was validated using genotype and clinical data from the UK Biobank (HR = 0.74, p = 0.04). In addition to the identification of ARID3B expression in normal colon tissue as a candidate prognostic biomarker for obese CRC patients, our study illustrates the challenges of genotype-based prediction of gene expression, and the advantage of reassessing the prediction accuracy in a subset of the study population using measured gene expression data.

The HaemAtlas: Characterising Gene Expression in Differentiated Human Blood Cells

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2453-2453
Author(s):  
Nicholas A. Watkins ◽  
Marloes R. Tijssen ◽  
Arief Gusnanto ◽  
Bernard de Bono ◽  
Subhajyoti De ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
Transcription Factors ◽  
Cell Function ◽  
Expression Profiles ◽  
Association Studies ◽  
Cytotoxic T Cells ◽  
Expression Patterns ◽  
Immunoglobulin Superfamily ◽  
Genome Wide Association Studies

Abstract Haematopoiesis is a carefully controlled process that is regulated by complex networks of transcription factors that are, in part, controlled by signals resulting from ligand binding to cell surface receptors. In order to further understand haematopoiesis, we have compared gene expression profiles of human erythroblasts, megakaryocytes, B-cells, cytotoxic and helper T-cells, Natural Killer cells, granulocytes and monocytes using whole genome microarrays. A bioinformatics analysis of this data was performed focusing on transcription factors, immunoglobulin superfamily members and lineage specific transcripts. We observed that the numbers of lineage specific genes varies by two orders of magnitude, ranging from five for cytotoxic T cells to 878 for granulocytes. In addition, we have identified novel co-expression patterns for key transcription factors involved in haematopoiesis (eg. GATA3–GFI1 and GATA2–KLF1). This study represents the most comprehensive analysis of gene expression in haematopoietic cells to date and has identified genes that play key roles in lineage commitment and cell function. The data, which is freely accessible, will be invaluable for future studies on haematopoiesis and the role of specific genes and will also aid the understanding of the recent genome-wide association studies.

scholarly journals Proteomics as a Potential Tool for Identifying Biomarkers for Host Resistance to Cattle Tick

Proceedings ◽  
2020 ◽  
Vol 36 (1) ◽  
pp. 131
Author(s):  
Ali Raza ◽  
Peter James ◽  
Ala Tabor
Keyword(s):  
Gene Expression ◽  
Host Resistance ◽  
Serum Proteins ◽  
Expression Profiles ◽  
Association Studies ◽  
Gene Expression Profiles ◽  
Economic Losses ◽  
Effective Vaccine ◽  
Cattle Tick ◽  
Genome Wide Association Studies

The cattle tick, Rhiphicephalus microplus, and the diseases it transmits lead to massive economic losses to cattle industries in tropical and subtropical countries. The emergence of widespread resistance to acaricide drugs and the absence of an effective vaccine for tick control had led to genetic selection of host resistance as a method of choice for non-chemical control of cattle tick. Research to identify host genetic markers associated with tick susceptibility or resistance has been limited to the comparison of local breeds in specific geographic regions. Previous studies have also focused on gene expression profiles, localizing cellular and humoral immune responses, and genome-wide association studies (GWAS) to identify functional genetic variants associated with tick resistance/susceptibility. Given the fact that gene expression results and actual dynamics occurring at the protein level often do not correlate due to post-transcriptional, post-translational and degradation regulation, host proteomics may provide reliable biomarkers to assist in selection to support traditional breeding programs. The present study aims to investigate the variation in protein profiles among tick resistant and susceptible cattle following tick infestation. Preliminary findings suggest that different serum proteins exist between tick resistant and susceptible Santa Gertrudis cattle. This research is supported by Meat & Livestock Australia.

scholarly journals TWENTY-FOUR GENES ARE UPREGULATED IN PATIENTS WITH HYPOSPADIAS

2013 ◽  
Vol 16 (2) ◽  
pp. 39-43 ◽  
Author(s):  
R. Karabulut ◽  
Z. Turkyilmaz ◽  
K. Sonmez ◽  
G. Kumas ◽  
Sg. Ergun ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Profiles ◽  
Association Studies ◽  
Gene Expression Profiles ◽  
Ventral Surface ◽  
Genome Wide Association Studies ◽  
Expression Array ◽  
Large Patient ◽  
Expression Studies ◽  
Genome Wide

ABSTRACT Hypospadias is a congenital hypoplasia of the penis, with displacement of the urethral opening along the ventral surface, and has been reported to be one of the most common congenital anomalies, occurring in approximately 1:250 to 1:300 live births. As hypospadias is reported to be an easily diagnosed malformation at the crossroads of genetics and environment, it is important to study the genetic component in order to elucidate its etiology. In this study, the gene expression profiles both in human hypospadias tissues and normal penile tissues were studied by Human Gene Expression Array. Twentyfour genes were found to be upregulated. Among these, ATF3 and CYR61 have been reported previously. Other genes that have not been previously reported were also found to be upregulated: BTG2, CD69, CD9, DUSP1, EGR1, EIF4A1, FOS, FOSB, HBEGF, HNRNPUL1, IER2, JUN, JUNB, KLF2, NR4A1, NR4A2, PTGS2, RGS1, RTN4, SLC25A25, SOCS3 and ZFP36 (p <0.05). Further studies including genome-wide association studies (GWAS) with expression studies in a large patient group will help us for identifiying the candidate gene(s) in the etiology of hypospadias

scholarly journals mTOR complex 1 pathway activation in severe keratoconus; the functional implications of GWAS identified loci

2018 ◽  
Author(s):  
Robert PL Wisse ◽  
Jonas JW Kuiper ◽  
Gijsbert M de Veij Mestdagh ◽  
Catharina GK Wichers ◽  
Sanne Hiddingh ◽  
...  
Keyword(s):  
Gene Expression ◽  
Vision Loss ◽  
Expression Profiles ◽  
Association Studies ◽  
Corneal Thickness ◽  
Corneal Tissue ◽  
Genome Wide Association Studies ◽  
Corneal Grafting ◽  
Functional Implications ◽  
Mtorc1 Pathway

AbstractPurposeKeratoconus (KC) is an eye condition that can lead to a severe vision loss and may warrant a corneal grafting procedure. Meta-analyses of genome wide association studies have identified several genes that confer risks for differences in corneal curvature, corneal thickness, and developing keratoconus. Currently, there is limited evidence of a functional role for the identified loci in the affected corneal tissues.MethodsWe investigated the gene expression profiles of 4 GWAS confirmed risk loci and several related pathways that function in cellular ageing and cell cycle control in corneal tissue of a discovery and replication cohort comprising in total 27 keratoconus patients, 16 healthy controls, and 21 diseased controls (failed corneal grafts).ResultsWe confirmed the MTOR gene locus as differentially expressed in KC corneas in a discovery cohort Next, we replicated these results in a second cohort and found evidence of increased expression of various mTORC1 pathway signature genes, namely MTOR itself (P=0.040), AKT1 (P=0.028), IGF1R (P=0.022) and RAPTOR (P=0.007).ConclusionsGene expression profiling in cornea tissues revealed robust up-regulation of the mTORC1 pathway in KC and substantiates a potential role for this pathway in its pathogenesis. Functional implications should be further studied since biomarkers for disease activity are needed and selective targeting of the mTOR pathway is a promising treatment concept.

scholarly journals PrediXcan: Trait Mapping Using Human Transcriptome Regulation

2015 ◽  
Author(s):  
Eric R Gamazon ◽  
Heather E Wheeler ◽  
Kaanan Shah ◽  
Sahar V Mozaffari ◽  
Keston Aquino-Michaels ◽  
...  
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Prediction Models ◽  
Association Studies ◽  
Regulatory Function ◽  
Genetic Profile ◽  
Genome Wide Association Studies ◽  
Reverse Causality ◽  
Reference Transcriptome ◽  
Regulated Gene Expression

Genome-wide association studies (GWAS) have identified thousands of variants robustly associated with complex traits. However, the biological mechanisms underlying these associations are, in general, not well understood. We propose a gene-based association method called PrediXcan that directly tests the molecular mechanisms through which genetic variation affects phenotype. The approach estimates the component of gene expression determined by an individual's genetic profile and correlates the “imputed” gene expression with the phenotype under investigation to identify genes involved in the etiology of the phenotype. The genetically regulated gene expression is estimated using whole-genome tissue-dependent prediction models trained with reference transcriptome datasets. PrediXcan enjoys the benefits of gene- based approaches such as reduced multiple testing burden, more comprehensive annotation of gene function compared to that derived from single variants, and a principled approach to the design of follow-up experiments while also integrating knowledge of regulatory function. Since no actual expression data are used in the analysis of GWAS data - only in silico expression - reverse causality problems are largely avoided. PrediXcan harnesses reference transcriptome data for disease mapping studies. Our results demonstrate that PrediXcan can detect known and novel genes associated with disease traits and provide insights into the mechanism of these associations.

Epidermal growth factor (EGF) A61G polymorphism and EGF gene expression in normal colon tissue from patients with colorectal cancer

2007 ◽  
Vol 46 (8) ◽  
pp. 1113-1117 ◽  
Author(s):  
Karen-Lise G. Spindler ◽  
Jens N. Nielsen ◽  
Dorthe Ornskov ◽  
Ivan Brandslund ◽  
Anders Jakobsen
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Normal Colon ◽  
Colon Tissue ◽  
Normal Colon Tissue ◽  
Epidermal Growth
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