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Celiac disease microarray analysis based on System Biology Approach.

ABSTRACT: Aim of this study is screen of the large numbers of related genes of CD to find the key ones.Celiac disease (CD) is known as a gluten sensitive and immune system dependent disease. There are several high throughput investigations about CD but it is necessary to clarify new molecular aspects mechanism of celiac.Whole-genome profile (RNA) of the human peripheral blood mononuclear cells (PBMCs) as Gene expression profile GSE113469 was retrieved Gene Expression Omnibus (GEO) database. The significant genes were selected and analyzed via protein-protein interaction (PPI) network by Cytoscape software. The key genes were introduced and enriched via ClueGO to find the related biochemical pathways.Among 250 significant genes 47 genes with expressed change above 2 fold change (FC) were interacted and the constructed network were analyzed. The network characterized by poor connections so it was promoted by addition 50 related nodes and 18 crucial nodes were introduced. Two clusters of biochemical pathways were identified and discussed.There is an obvious conflict between microarray finding and the well-known related genes of CD. This problem can be solve by more attention to the interpretation of PPI ntwork analysis results.

SUBMITTER: Rezaei Tavirani M

PROVIDER: S-EPMC6040039 | biostudies-other | 2018

REPOSITORIES: biostudies-other

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Celiac disease microarray analysis based on System Biology Approach.

Rezaei Tavirani Mostafa M Bashash Davood D Tajik Rostami Fatemeh F Rezaei Tavirani Sina S Nikzamir Abdolrahim A Rezaei Tavirani Majid M Haidary Mohammad Hossain MH

Gastroenterology and hepatology from bed to bench 20180101 3

<h4>Aim</h4>Aim of this study is screen of the large numbers of related genes of CD to find the key ones.<h4>Background</h4>Celiac disease (CD) is known as a gluten sensitive and immune system dependent disease. There are several high throughput investigations about CD but it is necessary to clarify new molecular aspects mechanism of celiac.<h4>Methods</h4>Whole-genome profile (RNA) of the human peripheral blood mononuclear cells (PBMCs) as Gene expression profile GSE113469 was retrieved Gene Ex ...[more]

PMID: 30013745

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Project description:Microarray-based profiling represents an effective method to analyze cellular or tissue-specific gene expression on the genome-level. However, in comparative analyses between control and mutant samples, microarrays often identify a large number of differentially expressed genes, in turn making it challenging to isolate the select "high-priority candidates" that are most relevant to an observed mutant phenotype. Here, we describe an integrative approach for mouse mutant lens microarray gene expression analysis using publically accessible systems-level information such as wild-type mouse lens expression data in iSyTE (integrated Systems Tool for Eye gene discovery), protein-protein interaction data in public databases, gene ontology enrichment data, and transcription factor binding profile data. This strategy, when applied to small Maf Mafg-/-:Mafk+/- mouse lens microarray datasets (deposited in NCBI Gene Expression Omnibus database with accession number GSE65500) in Agrawal et al. 2015 [1], led to the effective prioritization of candidate genes linked to lens defects in these mutants. Indeed, from the original list of genes that are differentially expressed at ±1.5-fold and p<0.05 in Mafg-/-:Mafk+/- mutant lenses, this analysis led to the identification of thirty-six high-priority candidates, in turn reducing the number of genes for further study by approximately 1/3rd of the total. Moreover, eight of these genes are linked to mammalian cataract in the published literature, validating the efficacy of this approach. Additionally, these high-priority candidates contribute valuable information for the assembly of a gene regulatory network in the lens. In sum, the pipeline outlined in this report represents an effective approach for initial as well as downstream microarray expression data analysis to identify genes important for lens biology and cataracts. We anticipate that this integrative strategy can be extended to prioritize phenotypically relevant candidate genes from microarray data in other cells and tissues.

Project description:BackgroundBlood-based diagnostics has the potential to simplify the process of diagnosing celiac disease (CD). Although high levels of autoantibodies against tissue transglutaminase (anti-TG2) are strongly indicative of active CD, several other scenarios involve a need for additional blood-based CD markers.MethodsWe investigated the levels of messenger RNA (mRNA) in whole blood (n?=?49) and protein in plasma (n?=?22) from cases with active CD (n?=?20), with confirmed CD and normalized histology (n?=?15), and without a CD diagnosis (n?=?14). Group differences were analyzed using Kruskal-Wallis one-way analysis of variance by ranks. We also investigated correlations between levels of potential markers, histopathology according to the modified Marsh scale, and CD risk gradient based on HLA type, using Spearman rank correlation. The relation between HLA-DQ2 gene dose effect and the expression levels of selected blood-based markers was investigated using the Mann-Whitney U test. Finally, the diagnostic performance of anti-TG2, potential blood-based CD markers, and logistic regression models of combined markers was evaluated using receiver operating characteristic (ROC) curve analysis.ResultsCXCL11 protein levels and TNFRSF9 and TNFSF13B mRNA levels were identified as potential CD markers. These are all affected by or involved in the regulation of the NF-?B complex. CXCL11 protein levels and IL21 and IL15 mRNA levels were correlated with histopathology according to the modified Marsh scale, as were the established CD markers. HLA genotype risk and HLA-DQ2 gene dose effect did not show any significant relations with either the potential CD markers or the established CD markers. ROC curve analysis revealed a slight, non-significant increase in the area under the curve for the combined use of anti-TG2 and different constellations of potential blood-based CD markers compared to anti-TG2 alone.ConclusionsThe CD markers identified in this study further emphasize the significance of components related to NF-?B regulation in relation to CD. However, the relevance of CXCL11, TNFSF13B, TNFRSF9, and other NF-?B interacting proteins recognized by pathway analysis, needs to be further investigated in relation to diagnosis and monitoring of CD.

Project description:AIM:To develop a microarray-based prewarning system consisting of gastric cancer chip, prewarning data and analysis software for early detection of gastric cancer and pre-cancerous lesions. METHODS:Two high-density chips with 8,464 human cDNA sites were used to primarily identify potential genes specific for normal gastric mucosa, pre-cancerous lesion and gastric cancer. The low-density chips, composed of selected genes associated with normal gastric mucosa, precancerous lesion and gastric cancer, were fabricated and used to screen 150 specimens including 60 specimens of gastric cancer, 60 of pre-cancerous tissues and 30 of normal gastric mucosa. CAD software was used to screen out the relevant genes and their critical threshold values of expression levels distinguishing normal mucosa from pre-cancerous lesion and cancer. All data were stored in a computer database to establish a prewarning data library for gastric cancer. Two potential markers brcaa1 and ndr1 were identified by Western blot and immunohistochemistry. RESULTS:A total of 412 genes associated with three stages of gastric cancer development were identified. There were 216 genes displaying higher expression in gastric cancer, 85 genes displaying higher expression in pre-cancerous lesion and 88 genes displaying higher expression in normal gastric mucosa. Also 15 genes associated with metastasis of gastric cancer and 8 genes associated with risk factors were screened out for target genes of diagnosis chip of early gastric cancer. The threshold values of 412 selected genes to distinguish gastric cancer, pre-cancerous lesion from normal gastric mucosa were defined as 6.01+/-2.40, 4.86+/-1.94 and 5.42+/-2.17, respectively. These selected 412 genes and critical threshold values were compiled into an analysis software, which can automatically provide reports by analyzing the results of 412 genes obtained by examining gastric tissues. All data were compiled into a prewarning database for gastric cancer by CGO software. Northern blot and immunohistochemistry analysis confirmed that gene and protein of brcaa1 displayed lower expression in normal gastric mucosa and higher expression in gastric cancer tissues, conversely, ndr1 displayed lower expression in gastric cancer and higher expression in normal gastric mucosa. CONCLUSION:The microarray-based prewarning system for gastric cancer was developed. This system consisted of gastric cancer-associated gene chip, prewarning data and analysis software, which has a high potential for applications in the early detection of gastric cancer. The two potential markers brcaa1 and ndr1 identified may be used to distinguish cancer status fand non-cancer status.

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Celiac disease microarray analysis based on System Biology Approach.

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Celiac disease microarray analysis based on System Biology Approach.

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