Identification and characterization of differentially expressed genes in Type 2 Diabetes using in silico approach

被引:20
作者
Gupta, Manoj Kumar [1 ]
Vadde, Ramakrishna [1 ]
机构
[1] Yogi Vemana Univ, Dept Biotechnol & Bioinformat, Kadapa 516003, Andhra Prades, India
关键词
Type; 2; diabetes; Microarray; GWAS; Differential gene expression; Hub genes; MONOCYTE CHEMOATTRACTANT PROTEIN-1; BREAST-CANCER METASTASIS; C-FOS EXPRESSION; RHEUMATOID-ARTHRITIS; INSULIN-RESISTANCE; GROWTH-FACTOR; TARGET GENES; RISK; ASSOCIATION; MICRORNAS;
D O I
10.1016/j.compbiolchem.2019.01.010
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Diabetes mellitus is clinically characterized by hyperglycemia. Though many studies have been done to understand the mechanism of Type 2 Diabetes (T2D), however, the complete network of diabetes and its associated disorders through polygenic involvement is still under debate. The present study designed to re-analyze publicly available T2D related microarray raw datasets present in GEO database and T2D genes information present in GWAS catalog for screening out differentially expressed genes (DEGs) and identify key hub genes associated with T2D. T2D related microarray data downloaded from Gene Expression Omnibus (GEO) database and re-analysis performed with in house R packages scripts for background correction, normalization and identification of DEGs in T2D. Also retrieved T2D related DEGs information from GWAS catalog. Both DEGs lists were grouped after removal of overlapping genes. These screened DEGs were utilized further for identification and characterization of key hub genes in T2D and its associated diseases using STRING, WebGestalt and Panther databases. Computational analysis reveal that out of 99 identified key hub gene candidates from 348 DEGs, only four genes (CCL2, ELM01, VEGFA and TCF7L2) along with FOS playing key role in causing T2D and its associated disorders, like nephropathy, neuropathy, rheumatoid arthritis and cancer via p53 or Wnt signaling pathways. MIR-29, and MAZ_Q6 are identified potential target microRNA and TF along with probable drugs alprostadil, collagenase and dinoprostone for the key hub gene candidates. The results suggest that identified key DEGs may play promising roles in prevention of diabetes.
引用
收藏
页码:24 / 35
页数:12
相关论文
共 96 条
[1]   Treatment of arthritis with a selective inhibitor of c-Fos/activator protein-1 [J].
Aikawa, Yukihiko ;
Morimoto, Kimiko ;
Yamamoto, Tetsuya ;
Chaki, Hisaaki ;
Hashiramoto, Akira ;
Narita, Hirokazu ;
Hirono, Shuichi ;
Shiozawa, Shunichi .
NATURE BIOTECHNOLOGY, 2008, 26 (07) :817-823
[2]   Dominant negative mutations in human PPARγ associated with severe insulin resistance, diabetes mellitus and hypertension [J].
Barroso, I ;
Gurnell, M ;
Crowley, VEF ;
Agostini, M ;
Schwabe, JW ;
Soos, MA ;
Maslen, GL ;
Williams, TDM ;
Lewis, H ;
Schafer, AJ ;
Chatterjee, VKK ;
O'Rahilly, S .
NATURE, 1999, 402 (6764) :880-883
[3]   MicroRNAs: Genomics, biogenesis, mechanism, and function (Reprinted from Cell, vol 116, pg 281-297, 2004) [J].
Bartel, David P. .
CELL, 2007, 131 (04) :11-29
[4]  
Bastian M., Gephi: an Open Source Software for Exploring and Manipulating Networks, DOI 10.1609/icwsm.v3i1.13937
[5]   Age-dependent regulation of tumor-related microRNAs in the brain of the annual fish Nothobranchius furzeri [J].
Baumgart, Mario ;
Groth, Marco ;
Priebe, Steffen ;
Appelt, Jessika ;
Guthke, Reinhard ;
Platzer, Matthias ;
Cellerino, Alessandro .
MECHANISMS OF AGEING AND DEVELOPMENT, 2012, 133 (05) :226-233
[6]   Metabolic Regulation by p53 Family Members [J].
Berkers, Celia R. ;
Maddocks, Oliver D. K. ;
Cheung, Eric C. ;
Mor, Inbal ;
Vousden, Karen H. .
CELL METABOLISM, 2013, 18 (05) :617-633
[7]   Cessation of CCL2 inhibition accelerates breast cancer metastasis by promoting angiogenesis [J].
Bonapace, Laura ;
Coissieux, Marie-May ;
Wyckoff, Jeffrey ;
Mertz, Kirsten D. ;
Varga, Zsuzsanna ;
Junt, Tobias ;
Bentires-Alj, Mohamed .
NATURE, 2014, 515 (7525) :130-133
[8]   Inhibition of RANKL-induced osteoclast differentiation through the downregulation of c-Fos and NFATc1 by Eremochloa ophiuroides (centipedegrass) extract [J].
Choi, Bo-Yun ;
Park, Chul-Hong ;
Na, Yun Hee ;
Bai, Hyoung-Woo ;
Cho, Jae-Young ;
Chung, Byung Yeoup .
MOLECULAR MEDICINE REPORTS, 2016, 13 (05) :4014-4022
[9]   Effect of acute physiological hyperinsulinemia on gene expression in human skeletal muscle in vivo [J].
Coletta, Dawn K. ;
Balas, Bogdan ;
Chavez, Alberto O. ;
Baig, Muhammad ;
Abdul-Ghani, Muhammad ;
Kashyap, Sangeeta R. ;
Folli, Franco ;
Tripathy, Devjit ;
Mandarino, Lawrence J. ;
Cornell, John E. ;
DeFronzo, Ralph A. ;
Jenkinson, Christopher P. .
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 2008, 294 (05) :E910-E917
[10]   The genetic dissection of essential hypertension [J].
Cowley, Allen W., Jr. .
NATURE REVIEWS GENETICS, 2006, 7 (11) :829-840