Identification of key genes associated with multiple sclerosis based on gene expression data from peripheral blood mononuclear cells

被引:14
作者
Shang, Zhenwei [1 ,2 ,3 ]
Sun, Wenjing [1 ,2 ]
Zhang, Mingming [1 ,2 ,3 ]
Xu, Lidan [1 ,2 ]
Jia, Xueyuan [1 ,2 ]
Zhang, Ruijie [3 ]
Fu, Songbin [1 ,2 ]
机构
[1] Harbin Med Univ, Lab Med Genet, Harbin, Peoples R China
[2] Harbin Med Univ, Key Lab Preservat Human Genet Resources & Dis Con, Minist Educ, Harbin, Peoples R China
[3] Harbin Med Univ, Coll Bioinformat Sci & Technol, Harbin, Peoples R China
关键词
Multiple sclerosis; Protein protein interaction networks; miRNA; SNP; Enrichment anclysis; Interaction; CAUSE-SPECIFIC MORTALITY; SYSTEMATIC ANALYSIS; GLOBAL BURDEN; ALL-CAUSE; DISEASE; SUSCEPTIBILITY; OAS1; ARRAYEXPRESS; CONSUMPTION; SEVERITY;
D O I
10.7717/peerj.8357
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The aim of this study was to identify the potential key candidate genes of multiple sclerosis (MS) and uncover mechanisms in MS. We combined data from the microarray expression profile of three MS stages and performed bioinformatics analysis. Differentially expressed genes (DEGs) were identified among the distinct stages of MS and healthy controls, and a total of 349 shared DEGs were identified. Gene ontology (GO) and pathway enrichment analyses showed that the DEGs were significantly enriched in the biological processes (BPs) of purine-related metabolic processes and signaling, especially the common DEGs, which were enriched in some immunological processes. Most of the DEGs were enriched in signaling pathways associated with the immune system, some immune diseases and infectious disease pathways. Through a protein-protein interaction (PPI) network analysis and a gene expression regulatory network constructed with MS-related miRNAs, we confirmed FOS, TP53, VEGFA, JUN, HIF1A, RB1, PTGS2, CXCL8, OAS2, NFKB1A and OAS1 as candidate genes of MS. Furthermore , we explored the potential SNPs associated with MS by database mining. In conclusion, this study provides the identified genes, SNPs, biological processes, and cellular pathways associated with MS. The uncovered candidate genes may be potential biomarkers involved in the diagnosis and therapy of MS.
引用
收藏
页数:20
相关论文
共 45 条
[1]   An automated method for finding molecular complexes in large protein interaction networks [J].
Bader, GD ;
Hogue, CW .
BMC BIOINFORMATICS, 2003, 4 (1)
[2]   Characterization of the effects of immunomodulatory drug fingolimod (FTY720) on human T cell receptor signaling pathways [J].
Baer, Alan ;
Colon-Moran, Winston ;
Bhattarai, Nirjal .
SCIENTIFIC REPORTS, 2018, 8
[3]   Network biology:: Understanding the cell's functional organization [J].
Barabási, AL ;
Oltvai, ZN .
NATURE REVIEWS GENETICS, 2004, 5 (02) :101-U15
[4]   Emergence of scaling in random networks [J].
Barabási, AL ;
Albert, R .
SCIENCE, 1999, 286 (5439) :509-512
[5]   Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis [J].
Beecham, Ashley H. ;
Patsopoulos, Nikolaos A. ;
Xifara, Dionysia K. ;
Davis, Mary F. ;
Kemppinen, Anu ;
Cotsapas, Chris ;
Shah, Tejas S. ;
Spencer, Chris ;
Booth, David ;
Goris, An ;
Oturai, Annette ;
Saarela, Janna ;
Fontaine, Bertrand ;
Hemmer, Bernhard ;
Martin, Claes ;
Zipp, Frauke ;
D'Alfonso, Sandra ;
Martinelli-Boneschi, Filippo ;
Taylor, Bruce ;
Harbo, Hanne F. ;
Kockum, Ingrid ;
Hillert, Jan ;
Olsson, Tomas ;
Ban, Maria ;
Oksenberg, Jorge R. ;
Hintzen, Rogier ;
Barcellos, Lisa F. ;
Agliardi, Cristina ;
Alfredsson, Lars ;
Alizadeh, Mehdi ;
Anderson, Carl ;
Andrews, Robert ;
Sondergaard, Helle Bach ;
Baker, Amie ;
Band, Gavin ;
Baranzini, Sergio E. ;
Barizzone, Nadia ;
Barrett, Jeffrey ;
Bellenguez, Celine ;
Bergamaschi, Laura ;
Bernardinelli, Luisa ;
Berthele, Achim ;
Biberacher, Viola ;
Binder, Thomas M. C. ;
Blackburn, Hannah ;
Bomfim, Izaura L. ;
Brambilla, Paola ;
Broadley, Simon ;
Brochet, Bruno ;
Brundin, Lou .
NATURE GENETICS, 2013, 45 (11) :1353-+
[6]   ArrayExpress - a public repository for microarray gene expression data at the EBI [J].
Brazma, A ;
Parkinson, H ;
Sarkans, U ;
Shojatalab, M ;
Vilo, J ;
Abeygunawardena, N ;
Holloway, E ;
Kapushesky, M ;
Kemmeren, P ;
Lara, GG ;
Oezcimen, A ;
Rocca-Serra, P ;
Sansone, SA .
NUCLEIC ACIDS RESEARCH, 2003, 31 (01) :68-71
[7]   Smoking and Risk of Multiple Sclerosis Evidence of Modification by NAT1 Variants [J].
Briggs, Farren B. S. ;
Acuna, Brigid ;
Shen, Ling ;
Ramsay, Patricia ;
Quach, Hong ;
Bernstein, Allan ;
Bellesis, Kalliope H. ;
Kockum, Ingrid S. ;
Hedstrom, Anna K. ;
Alfredsson, Lars ;
Olsson, Tomas ;
Schaefer, Catherine ;
Barcellos, Lisa F. .
EPIDEMIOLOGY, 2014, 25 (04) :605-614
[8]   Identification of a new susceptibility variant for multiple sclerosis in OAS1 by population genetics analysis [J].
Cagliani, Rachele ;
Fumagalli, Matteo ;
Guerini, Franca R. ;
Riva, Stefania ;
Galimberti, Daniela ;
Comi, Giacomo P. ;
Agliardi, Cristina ;
Scarpini, Elio ;
Pozzoli, Uberto ;
Forni, Diego ;
Caputo, Domenico ;
Asselta, Rosanna ;
Biasin, Mara ;
Paraboschi, Elvezia M. ;
Bresolin, Nereo ;
Clerici, Mario ;
Sironi, Manuela .
HUMAN GENETICS, 2012, 131 (01) :87-97
[9]   Increased frequencies of circulating CXCL10-, CXCL8-and CCL4-producing monocytes and Siglec-3-expressing myeloid dendritic cells in systemic sclerosis patients [J].
Carvalheiro, Tiago ;
Horta, Sara ;
van Roon, Joel A. G. ;
Santiago, Mariana ;
Salvador, Maria J. ;
Trindade, Helder ;
Radstake, Timothy R. D. J. ;
da Silva, Jose A. P. ;
Paiva, Artur .
INFLAMMATION RESEARCH, 2018, 67 (02) :169-177
[10]   Astrocytic TYMP and VEGFA drive blood-brain barrier opening in inflammatory central nervous system lesions [J].
Chapouly, Candice ;
Argaw, Azeb Tadesse ;
Horng, Sam ;
Castro, Kamilah ;
Zhang, Jingya ;
Asp, Linnea ;
Loo, Hannah ;
Laitman, Benjamin M. ;
Mariani, John N. ;
Farber, Rebecca Straus ;
Zaslavsky, Elena ;
Nudelman, German ;
Raine, Cedric S. ;
John, Gareth R. .
BRAIN, 2015, 138 :1548-1567