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Celiac disease microarray analysis based on system biology approach

Mostafa Rezaei –Tavirani, Davood Bashash, Fatemeh Tajik Rostami, Sina Rezaei Tavirani, Abdolrahim Nikzamir, Majid Rezaei Tavirani, Mohammad Hossain Haidari




Aim: Aim of this study is screen of the large numbers of related genes of CD to find the key ones.

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Celiac disease, System biology, Crucial genes, Cytoscape, ClueGO.

(Please cite as: Rezaei Tavirani M, Bashash D, Tajik Rostami F, Rezaei Tavirani S, Nikzamir A, Rezaei Tavirani M, et al. Celiac Disease Microarray Analysis based on System Biology Approach. Gastroenterol Hepatol Bed Bench 2018;11(3):216-224).


Celiac disease, System biology, Crucial genes, Cytoscape, ClueGO


Norris JM, Barriga K, Hoffenberg EJ, Taki I, Miao D, Haas JE, et al. Risk of celiac disease autoimmunity and timing of gluten introduction in the diet of infants at increased risk of disease. Jama. 2005;293(19):2343-51.

Fasano A, Catassi C. Current approaches to diagnosis and treatment of celiac disease: an evolving spectrum. Gastroenterology. 2001;120(3):636-51.

Kemppainen T, Kröger H, Janatuinen E, Arnala I, Kosma V-M, Pikkarainen P, et al. Osteoporosis in adult patients with celiac disease. Bone. 1999;24(3):249-55.

Hershko C, Hoffbrand AV, Keret D, Souroujon M, Maschler I, Monselise Y, et al. Role of autoimmune gastritis, Helicobacter pylori and celiac disease in refractory or unexplained iron deficiency anemia. haematologica. 2005;90(5):585-95.

Hill I. Epidemiology, pathogenesis, and clinical manifestations of celiac disease in children. UpToDate; 2017.

Catassi C, Fasano A. Celiac disease diagnosis: simple rules are better than complicated algorithms. The American journal of medicine. 2010;123(8):691-3.

Sollid LM, Lie BA. Celiac disease genetics: current concepts and practical applications. Clinical Gastroenterology and Hepatology. 2005;3(9):843-51.

Daulat AM, Puvirajesinghe TM, Camoin L, Borg J-P. Mapping cellular polarity networks using mass spectrometry-based strategies. Journal of Molecular Biology. 2018.


Feng Y, Spezia M, Huang S, Yuan C, Zeng Z, Zhang L, et al. Breast cancer development and progression: risk factors, cancer stem cells, signaling pathways, genomics, and molecular pathogenesis. Genes & Diseases. 2018.

Zhou J, Park C, Theesfeld C, Yuan Y, Sawicka K, Darnell J, et al. Whole-genome deep learning analysis reveals causal role of noncoding mutations in autism. bioRxiv. 2018:319681.

Stulík J, Hernychová L, Porkertová S, Pozler O, Tučková L, Sánchez D, et al. Identification of new celiac disease autoantigens using proteomic analysis. Proteomics. 2003;3(6):951-6.

Orrù S, Caputo I, D'Amato A, Ruoppolo M, Esposito C. Proteomics identification of acyl-acceptor and acyl-donor substrates for transglutaminase in a human intestinal epithelial cell line Implications for celiac disease. Journal of Biological Chemistry. 2003;278(34):31766-73.

van Heel DA, Franke L, Hunt KA, Gwilliam R, Zhernakova A, Inouye M, et al. A genome-wide association study for celiac disease identifies risk variants in the region harboring IL2 and IL21. Nature genetics. 2007;39(7):827.

Zhernakova A, Stahl EA, Trynka G, Raychaudhuri S, Festen EA, Franke L, et al. Meta-analysis of genome-wide association studies in celiac disease and rheumatoid arthritis identifies fourteen non-HLA shared loci. PLoS genetics. 2011;7(2):e1002004.

Karbalaei R, Allahyari M, Rezaei-Tavirani M, Asadzadeh-Aghdaei H, Zali MR. Protein-protein interaction analysis of Alzheimers disease and NAFLD based on systems biology methods unhide common ancestor pathways. Gastroenterology and Hepatology from bed to bench. 2018;11(1):27.

Azodi MZ, Peyvandi H, Rostami-Nejad M, Safaei A, Rostami K, Vafaee R, et al. Protein-protein interaction network of celiac disease. Gastroenterology and Hepatology from bed to bench. 2016;9(4):268.

Abbaszadeh H-A, Peyvandi AA, Sadeghi Y, Safaei A, Zamanian-Azodi M, Khoramgah MS, et al. Er: YAG laser and cyclosporin A effect on cell cycle regulation of human gingival fibroblast cells. Journal of lasers in medical sciences. 2017;8(3):143.

Ge Q, Chen L, Tang M, Zhang S, Gao L, Ma S, et al. Analysis of mulberry leaf components in the treatment of diabetes using network pharmacology. European Journal of Pharmacology. 2018.

Ye Z, Kong Q, Han J, Deng J, Wu M, Deng H. Circular RNAs are differentially expressed in liver ischemia/reperfusion injury model. Journal of cellular biochemistry. 2018.

Patil AK, Patil SS, Manickam P. Identification of Lung Cancer Related Genes Using Enhanced Floyd Warshall Algorithm in a Protein to Protein Interaction Network.

Jin B-J, Lee S, Verkman AS. Hollow Micropillar Array Method for High-Capacity Drug Screening on Filter-Grown Epithelial Cells. Analytical Chemistry. 2018.

Sabate J-M, Ameziane N, Lamoril J, Jouet P, Farmachidi J-P, Soule J-C, et al. The V249I polymorphism of the CX3CR1 gene is associated with fibrostenotic disease behavior in patients with Crohn's disease. European journal of gastroenterology & hepatology. 2008;20(8):748-55.

Garrote JA, Gómez E, León AJ, Bernardo D, Calvo C, Fernández-Salazar L, et al. Cytokine, chemokine and immune activation pathway profiles in celiac disease: an immune system activity screening by expression macroarrays. Drug Target Insights. 2008;3:DTI. S399.

Zou Y-R, Kottmann AH, Kuroda M, Taniuchi I, Littman DR. Function of the chemokine receptor CXCR4 in haematopoiesis and in cerebellar development. Nature. 1998;393(6685):595.

Chen Y, Jacamo R, Konopleva M, Garzon R, Croce C, Andreeff M. CXCR4 downregulation of let-7a drives chemoresistance in acute myeloid leukemia. The Journal of clinical investigation. 2013;123(6):2395-407.

Wulfaenger J, Niedling S, Riemann D, Seliger B. Aminopeptidase N (APN)/CD13-dependent CXCR4 downregulation is associated with diminished cell migration, proliferation and invasion. Molecular membrane biology. 2008;25(1):72-82.

Altaf-Ul-Amin M, Shinbo Y, Mihara K, Kurokawa K, Kanaya S. Development and implementation of an algorithm for detection of protein complexes in large interaction networks. BMC bioinformatics. 2006;7(1):207.

Rezaei-Tavirani M, Rezaei-Tavirani S, Ahmadi N, Naderi N, Abdi S. Pancreatic adenocarcinoma protein-protein interaction network analysis. Gastroenterology and Hepatology from bed to bench. 2017;10(Suppl1):S85.

Rezaei-Tavirani M, Rezaei-Tavirani M, Mansouri V, Mahdavi SM, Valizadeh R, Rostami-Nejad M, et al. Introducing crucial protein panel of gastric adenocarcinoma disease. Gastroenterology and Hepatology from bed to bench. 2017;10(1):21.

Rueda B, Núñez C, López-Nevot MÁ, Paz Ruiz M, Urcelay E, De La Concha EG, et al. Functional polymorphism of the NFKB1 gene promoter is not relevant in predisposition to celiac disease. Scandinavian journal of gastroenterology. 2006;41(4):420-3.

Dema B, Martinez A, Fernandez-Arquero M, Maluenda C, Polanco I, Figueredo MA, et al. The IL6-174G/C polymorphism is associated with celiac disease susceptibility in girls. Human immunology. 2009;70(3):191-4.

Malandrino N, Capristo E, Farnetti S, Leggio L, Abenavoli L, Addolorato G, et al. Metabolic and nutritional features in adult celiac patients. Digestive Diseases. 2008;26(2):128-33.

Kaukinen K, Salmi J, Lahtela J, Siljamaki-Ojansuu U. No effect of gluten-free diet on the metabolic control of type 1 diabetes in patients with diabetes and celiac disease. Diabetes Care. 1999;22(10):1747.

Scaramuzza AE, Mantegazza C, Bosetti A, Zuccotti GV. Type 1 diabetes and celiac disease: The effects of gluten free diet on metabolic control. World journal of diabetes. 2013;4(4):130.

Sujashvili R. Advantages of extracellular ubiquitin in modulation of immune responses. Mediators of inflammation. 2016;2016.

Barcellos LF, Caillier S, Dragone L, Elder M, Vittinghoff E, Bucher P, et al. PTPRC (CD45) is not associated with the development of multiple sclerosis in US patients. Nature genetics. 2001;29(1):23.

Porcu M, Kleppe M, Gianfelici V, Geerdens E, De Keersmaecker K, Tartaglia M, et al. Mutation of the receptor tyrosine phosphatase PTPRC (CD45) in T-cell acute lymphoblastic leukemia. Blood. 2012;119(19):4476-9.

Safari-Alighiarloo N, Rezaei-Tavirani M, Taghizadeh M, Tabatabaei SM, Namaki S. Network-based analysis of differentially expressed genes in cerebrospinal fluid (CSF) and blood reveals new candidate genes for multiple sclerosis. PeerJ. 2016;4:e2775.

Takeuchi O, Akira S. Innate immunity to virus infection. Immunological reviews. 2009;227(1):75-86.

Cho Y, Challa S, Moquin D, Genga R, Ray TD, Guildford M, et al. Phosphorylation-driven assembly of the RIP1-RIP3 complex regulates programmed necrosis and virus-induced inflammation. Cell. 2009;137(6):1112-23.

Takeuchi O, Akira S. Recognition of viruses by innate immunity. Immunological reviews. 2007;220(1):214-24.

Narita M, Nuñez S, Heard E, Narita M, Lin AW, Hearn SA, et al. Rb-mediated heterochromatin formation and silencing of E2F target genes during cellular senescence. Cell. 2003;113(6):703-16.

Semenza GL. HIF-1 and human disease: one highly involved factor. Genes & development. 2000;14(16):1983-91.

DOI: https://doi.org/10.22037/ghfbb.v0i0.1405