Research Article
Year 2021,
Volume: 9 Issue: 2, 479 - 489, 01.06.2021
Abstract
Behçet Hastalığı, vücutta kan damarı iltihabına neden olan ve tüm organ sistemlerini etkileyebilen nadir bir oto enflamatuar ve otoimmün hastalıktır. Hastalığın patofizyolojisi halen araştırılmaktadır.
Semptomlar değişkenlik gösterdiği için teşhis edilmesi zordur ve hastalık için yeterli tıbbi tedavi yoktur.
Bu çalışmada Behçet Hastalığı gen (izole edilmiş CD4 + T hücreleri ve CD14 + monositlerinden örnekler) ve miRNA ekspresyonu (trombosit içermeyen plazmadan örnekler) veri setleri istatistiksel olarak analiz edilmiştir. CD4 + T hücreleri ve CD14 + monositleri için farklı şekilde ifade edilen genler tanımlanmış ve bu verilerle ilişkili miRNA listelenmiştir. Protein-protein ve miRNA - hedef gen etkileşim ağları oluşturulmuş ve bu ağların merkezi olanları her iki hücre tipi için belirlenmiştir. Gen ekspresyon verileri ile ilişkili metabolitler ve metabolik yollar ortaya konulmuş ve ilişkili sinyal yollarını ve hastalıklarını tanımlamak için zenginleştirme analizi yapılmıştır. Trombosit içermeyen plazma örneklerinin farklı olarak ifade edilen miRNA'ları da tanımlanmıştır. Analiz sonuçları, hücre/doku tipine bağlı genomik yeniden programlamayı göstermiştir. Tüm hücre/doku türlerinde merkezi miRNAlar (hsa-miR-17-5p, hsa-miR-603, hsa-miR-375, hsa-miR-107, hsa-miR-454-3p, hsa-miR-650, hsa-miR-142-3p and hsa-miR-765) ve CD4 + ve CD14 + hücreleri için metabolitler (guanidinoasetat ve histon-L-lizin) biyobelirteç adayları olarak belirlenmiştir. Gelecekte yapılacak olan ve bu aday biyobelirteçlere odaklanan deneysel çalışmalar ile bir teşhis kiti veya geliştirilmiş terapötiklerin tasarımı gerçekleştirilebilir.
References
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- Akpolat T, Dilek M, Aksu K, et al (2008) Renal Behçet’s Disease: An Update. Semin Arthritis Rheum. https://doi.org/10.1016/j.semarthrit.2007.11.001
- Barrett T, Wilhite SE, Ledoux P, et al (2013) NCBI GEO: Archive for functional genomics data sets - Update. Nucleic Acids Res. https://doi.org/10.1093/nar/gks1193
- ,Benjamini Y, Hochberg Y (1995) Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing. J R Stat Soc Ser B. https://doi.org/10.1111/j.2517- 6161.1995.tb02031.x
- Bertolazzi P, Bock ME, Guerra C (2013) On the functional and structural characterization of hubs in protein-protein interaction networks. Biotechnol. Adv.
- Bouillet L, Baudet AE, Deroux A, et al (2013) Auto-antibodies to vascular endothelial cadherin in humans: Association with autoimmune diseases. Lab Investig. https://doi.org/10.1038/labinvest.2013.106
- Bovolenta LA, Acencio ML, Lemke N (2012) HTRIdb: an open-access database for experimentally verified human transcriptional regulation interactions. BMC Genomics. https://doi.org/10.1186/1471-2164-13-405
- Chatr-Aryamontri A, Oughtred R, Boucher L, et al (2017) The BioGRID interaction database: 2017 update. Nucleic Acids Res. https://doi.org/10.1093/nar/gkw1102
- Chen Y, Ding YY, Ren Y, et al (2018) Identification of differentially expressed MicroRNAs in acute Kawasaki disease. Mol Med Rep. https://doi.org/10.3892/mmr.2017.8016
- Chin CH, Chen SH, Wu HH, et al (2014) cytoHubba: Identifying hub objects and sub-networks from complex interactome. BMC Syst Biol. https://doi.org/10.1186/1752-0509-8-S4-S11
- Chou CH, Shrestha S, Yang CD, et al (2018) MiRTarBase update 2018: A resource for experimentally validated microRNA-target interactions. Nucleic Acids Res. https://doi.org/10.1093/nar/gkx1067
- Deng GM, Kyttaris VC, Tsokos GC (2016) Targeting syk in autoimmune rheumatic diseases. Front. Immunol.
- Excoffier L, Gouy A, Daub JT, et al (2017) Cytoscape: A Software Environment for Integrated Models of Biomolecular Interaction Networks. Nucleic Acids Res. https://doi.org/10.1093/nar/gkx626
- Foggin S, Mesquita-Ribeiro R, Dajas-Bailador F, Layfield R (2019) Biological significance of microRNA biomarkers in ALS-innocent bystanders or disease culprits? Front. Neurol.
- Gallelli L, Cione E, Peltrone F, et al (2019) Hsa-miR-34a-5p and hsa-miR-375 as Biomarkers for Monitoring the Effects of Drug Treatment for Migraine Pain in Children and Adolescents: A Pilot Study. J Clin Med. https://doi.org/10.3390/jcm8070928
- Garavelli L, Mainardi PC (2007) Mowat-Wilson syndrome. Orphanet J Rare Dis. https://doi.org/10.1186/1750-1172-2-42
- Goodarzi MO, Maher JF, Cui J, et al (2008) FEM1A and FEM1B: Novel candidate genes for polycystic ovary syndrome. Hum Reprod. https://doi.org/10.1093/humrep/den324
- Huang DW, Sherman BT, Lempicki RA (2009) Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. https://doi.org/10.1038/nprot.2008.211
- Jia SZ, Yang Y, Lang J, et al (2013) Plasma miR-17-5p, miR-20a and miR-22 are down-regulated in women with endometriosis. Hum Reprod. https://doi.org/10.1093/humrep/des413
- Kanehisa M, Furumichi M, Tanabe M, et al (2017) KEGG: New perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Res. https://doi.org/10.1093/nar/gkw1092
- López-Ibáñez J, Pazos F, Chagoyen M (2016) MBROLE 2.0-functional enrichment of chemical compounds. Nucleic Acids Res. https://doi.org/10.1093/nar/gkw253
- Mardinoglu A, Agren R, Kampf C, et al (2014) Genome-scale metabolic modelling of hepatocytes reveals serine deficiency in patients with non-alcoholic fatty liver disease. Nat Commun. https://doi.org/10.1038/ncomms4083
- Mkaddem S Ben, Benhamou M, Monteiro RC (2019) Understanding Fc receptor involvement in inflammatory diseases: From mechanisms to new therapeutic tools. Front. Immunol.
- Mudunuri U, Che A, Yi M, Stephens RM (2009) bioDBnet: The biological database network. Bioinformatics. https://doi.org/10.1093/bioinformatics/btn654
- O’Brien RJ, Wong PC (2011) Amyloid precursor protein processing and alzheimer’s disease. Annu Rev Neurosci. https://doi.org/10.1146/annurev-neuro-061010-113613
- Park JH (1999) Clinical analysis of Behçet disease: arthritic manifestations in Behçet disease may present as seronegative rheumatoid arthritis or palindromic rheumatism. Korean J Intern Med. https://doi.org/10.3904/kjim.1999.14.1.66
- Perazzio SF, Soeiro-Pereira P V., de Souza AWS, et al (2015) Behçet’s disease heterogeneity: Cytokine production and oxidative burst of phagocytes are altered in patients with severe manifestations. Clin Exp Rheumatol
- Puccetti A, Fiore PF, Pelosi A, et al (2018a) Gene expression profiling in behcet’s disease indicates an autoimmune component in the pathogenesis of the disease and opens new avenues for targeted therapy. J Immunol Res. https://doi.org/10.1155/2018/4246965
- Puccetti A, Pelosi A, Fiore PF, et al (2018b) MicroRNA expression profiling in behçet’s disease. J Immunol Res. https://doi.org/10.1155/2018/2405150
- Reilly MM, Murphy SM, Laurá M (2011) Charcot-Marie-Tooth disease. In: Journal of the Peripheral Nervous System
- Segundo-Val IS, Sanz-Lozano CS (2016) Introduction to the gene expression analysis. In: Methods in Molecular Biology
- Sevimoglu T, Arga KY (2014) The role of protein interaction networks in systems biomedicine. Comput Struct Biotechnol J 11:22–27. https://doi.org/10.1016/J.CSBJ.2014.08.008
- Smyth GK, Ritchie M, Thorne N (2011) Linear Models for Microarray Data User ’ s Guide. Bioinformatics. https://doi.org/10.1093/nar/gkv007
- Taylor SL, McGuckin MA, Wesselingh S, Rogers GB (2018) Infection’s Sweet Tooth: How Glycans Mediate Infection and Disease Susceptibility. Trends Microbiol.
- Tong B, Liu X, Xiao J, Su G (2019) Immunopathogenesis of Behcet’s disease. Front. Immunol.
- van der Houwen T, van Laar J (2020) Behҫet’s disease, and the role of TNF-α and TNF-α blockers. Int. J. Mol. Sci.
- Wang W, Dong R, Guo Y, et al (2019) CircMTO1 inhibits liver fibrosis via regulation of miR-17-5p and Smad7. J Cell Mol Med. https://doi.org/10.1111/jcmm.14432
- Wopereis S, Lefeber DJ, Morava É, Wevers RA (2006) Mechanisms in protein O-glycan biosynthesis and clinical and molecular aspects of protein O-glycan biosynthesis defects: A review. Clin. Chem.
- Wu CP, Bi YJ, Liu DM, Wang LY (2019) Hsa-miR-375 promotes the progression of inflammatory bowel disease by upregulating TLR4. Eur Rev Med Pharmacol Sci. https://doi.org/10.26355/eurrev_201909_18871
- Yao X, Zhang Y, Wu L, et al (2019) Immunohistochemical Study of NR2C2, BTG2, TBX19, and CDK2 Expression in 31 Paired Primary/Recurrent Nonfunctioning Pituitary Adenomas. Int J Endocrinol. https://doi.org/10.1155/2019/5731639
- Zhang C, Lu J, Liu B, et al (2016) Primate-specific miR-603 is implicated in the risk and pathogenesis of Alzheimer’s disease. Aging (Albany NY). https://doi.org/10.18632/aging.100887
Year 2021,
Volume: 9 Issue: 2, 479 - 489, 01.06.2021
Abstract
Behcet’s Disease is a rare auto inflammatory and autoimmune disorder that causes blood vessel inflammation throughout the body and can affect all organ systems. The pathophysiology of the disease is still under investigation. Since the symptoms are varying it is difficult to diagnose and there are no sufficient medical treatments for the disease. In this study Behcet’s Disease gene (Samples from isolated CD4+ T cells and CD14+ monocytes) and miRNA expression (samples from platelet free plasma) datasets were statistically analyzed. Differentially expressed genes for CD4+ T cells and CD14+ monocytes have been identified and miRNA associated with this data were listed. Protein-protein and miRNA – target gene interaction networks were constructed and hubs of these networks were identified for both cell types.
Metabolites and metabolic pathways associated with gene expression data were displayed and enrichment analysis was done to identify associated signaling pathways and diseases. Differentially expressed miRNAs of platelet free plasma samples were also identified. The analysis results indicated cell/tissue type dependent genomic reprogramming. Mutual hub miRNAs (hsa-miR-17-5p, hsa-miR-603, hsa-miR- 375, hsa-miR-107, hsa-miR-454-3p, hsa-miR-650, hsa-miR-142-3p and hsa-miR-765) in all cell/tissue types and metabolites (guanidinoacetate and histone-L-lysine) for CD4+ and CD14+ cells may be considered as biomarker candidates. Future studies focusing on these candidate biomarkers might yield a diagnostic kit or design of enhanced therapeutics for Behcet’s Disease.
References
- Agren R, Liu L, Shoaie S, et al (2013) The RAVEN Toolbox and Its Use for Generating a Genome-scale Metabolic Model for Penicillium chrysogenum. PLoS Comput Biol. https://doi.org/10.1371/journal.pcbi.1002980
- Ahn JK, Kim S, Kim J, et al (2015) A comparative metabolomic evaluation of behcet’s disease with arthritis and seronegative arthritis using synovial fluid. PLoS One. https://doi.org/10.1371/journal.pone.0135856
- Akpolat T, Dilek M, Aksu K, et al (2008) Renal Behçet’s Disease: An Update. Semin Arthritis Rheum. https://doi.org/10.1016/j.semarthrit.2007.11.001
- Barrett T, Wilhite SE, Ledoux P, et al (2013) NCBI GEO: Archive for functional genomics data sets - Update. Nucleic Acids Res. https://doi.org/10.1093/nar/gks1193
- ,Benjamini Y, Hochberg Y (1995) Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing. J R Stat Soc Ser B. https://doi.org/10.1111/j.2517- 6161.1995.tb02031.x
- Bertolazzi P, Bock ME, Guerra C (2013) On the functional and structural characterization of hubs in protein-protein interaction networks. Biotechnol. Adv.
- Bouillet L, Baudet AE, Deroux A, et al (2013) Auto-antibodies to vascular endothelial cadherin in humans: Association with autoimmune diseases. Lab Investig. https://doi.org/10.1038/labinvest.2013.106
- Bovolenta LA, Acencio ML, Lemke N (2012) HTRIdb: an open-access database for experimentally verified human transcriptional regulation interactions. BMC Genomics. https://doi.org/10.1186/1471-2164-13-405
- Chatr-Aryamontri A, Oughtred R, Boucher L, et al (2017) The BioGRID interaction database: 2017 update. Nucleic Acids Res. https://doi.org/10.1093/nar/gkw1102
- Chen Y, Ding YY, Ren Y, et al (2018) Identification of differentially expressed MicroRNAs in acute Kawasaki disease. Mol Med Rep. https://doi.org/10.3892/mmr.2017.8016
- Chin CH, Chen SH, Wu HH, et al (2014) cytoHubba: Identifying hub objects and sub-networks from complex interactome. BMC Syst Biol. https://doi.org/10.1186/1752-0509-8-S4-S11
- Chou CH, Shrestha S, Yang CD, et al (2018) MiRTarBase update 2018: A resource for experimentally validated microRNA-target interactions. Nucleic Acids Res. https://doi.org/10.1093/nar/gkx1067
- Deng GM, Kyttaris VC, Tsokos GC (2016) Targeting syk in autoimmune rheumatic diseases. Front. Immunol.
- Excoffier L, Gouy A, Daub JT, et al (2017) Cytoscape: A Software Environment for Integrated Models of Biomolecular Interaction Networks. Nucleic Acids Res. https://doi.org/10.1093/nar/gkx626
- Foggin S, Mesquita-Ribeiro R, Dajas-Bailador F, Layfield R (2019) Biological significance of microRNA biomarkers in ALS-innocent bystanders or disease culprits? Front. Neurol.
- Gallelli L, Cione E, Peltrone F, et al (2019) Hsa-miR-34a-5p and hsa-miR-375 as Biomarkers for Monitoring the Effects of Drug Treatment for Migraine Pain in Children and Adolescents: A Pilot Study. J Clin Med. https://doi.org/10.3390/jcm8070928
- Garavelli L, Mainardi PC (2007) Mowat-Wilson syndrome. Orphanet J Rare Dis. https://doi.org/10.1186/1750-1172-2-42
- Goodarzi MO, Maher JF, Cui J, et al (2008) FEM1A and FEM1B: Novel candidate genes for polycystic ovary syndrome. Hum Reprod. https://doi.org/10.1093/humrep/den324
- Huang DW, Sherman BT, Lempicki RA (2009) Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. https://doi.org/10.1038/nprot.2008.211
- Jia SZ, Yang Y, Lang J, et al (2013) Plasma miR-17-5p, miR-20a and miR-22 are down-regulated in women with endometriosis. Hum Reprod. https://doi.org/10.1093/humrep/des413
- Kanehisa M, Furumichi M, Tanabe M, et al (2017) KEGG: New perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Res. https://doi.org/10.1093/nar/gkw1092
- López-Ibáñez J, Pazos F, Chagoyen M (2016) MBROLE 2.0-functional enrichment of chemical compounds. Nucleic Acids Res. https://doi.org/10.1093/nar/gkw253
- Mardinoglu A, Agren R, Kampf C, et al (2014) Genome-scale metabolic modelling of hepatocytes reveals serine deficiency in patients with non-alcoholic fatty liver disease. Nat Commun. https://doi.org/10.1038/ncomms4083
- Mkaddem S Ben, Benhamou M, Monteiro RC (2019) Understanding Fc receptor involvement in inflammatory diseases: From mechanisms to new therapeutic tools. Front. Immunol.
- Mudunuri U, Che A, Yi M, Stephens RM (2009) bioDBnet: The biological database network. Bioinformatics. https://doi.org/10.1093/bioinformatics/btn654
- O’Brien RJ, Wong PC (2011) Amyloid precursor protein processing and alzheimer’s disease. Annu Rev Neurosci. https://doi.org/10.1146/annurev-neuro-061010-113613
- Park JH (1999) Clinical analysis of Behçet disease: arthritic manifestations in Behçet disease may present as seronegative rheumatoid arthritis or palindromic rheumatism. Korean J Intern Med. https://doi.org/10.3904/kjim.1999.14.1.66
- Perazzio SF, Soeiro-Pereira P V., de Souza AWS, et al (2015) Behçet’s disease heterogeneity: Cytokine production and oxidative burst of phagocytes are altered in patients with severe manifestations. Clin Exp Rheumatol
- Puccetti A, Fiore PF, Pelosi A, et al (2018a) Gene expression profiling in behcet’s disease indicates an autoimmune component in the pathogenesis of the disease and opens new avenues for targeted therapy. J Immunol Res. https://doi.org/10.1155/2018/4246965
- Puccetti A, Pelosi A, Fiore PF, et al (2018b) MicroRNA expression profiling in behçet’s disease. J Immunol Res. https://doi.org/10.1155/2018/2405150
- Reilly MM, Murphy SM, Laurá M (2011) Charcot-Marie-Tooth disease. In: Journal of the Peripheral Nervous System
- Segundo-Val IS, Sanz-Lozano CS (2016) Introduction to the gene expression analysis. In: Methods in Molecular Biology
- Sevimoglu T, Arga KY (2014) The role of protein interaction networks in systems biomedicine. Comput Struct Biotechnol J 11:22–27. https://doi.org/10.1016/J.CSBJ.2014.08.008
- Smyth GK, Ritchie M, Thorne N (2011) Linear Models for Microarray Data User ’ s Guide. Bioinformatics. https://doi.org/10.1093/nar/gkv007
- Taylor SL, McGuckin MA, Wesselingh S, Rogers GB (2018) Infection’s Sweet Tooth: How Glycans Mediate Infection and Disease Susceptibility. Trends Microbiol.
- Tong B, Liu X, Xiao J, Su G (2019) Immunopathogenesis of Behcet’s disease. Front. Immunol.
- van der Houwen T, van Laar J (2020) Behҫet’s disease, and the role of TNF-α and TNF-α blockers. Int. J. Mol. Sci.
- Wang W, Dong R, Guo Y, et al (2019) CircMTO1 inhibits liver fibrosis via regulation of miR-17-5p and Smad7. J Cell Mol Med. https://doi.org/10.1111/jcmm.14432
- Wopereis S, Lefeber DJ, Morava É, Wevers RA (2006) Mechanisms in protein O-glycan biosynthesis and clinical and molecular aspects of protein O-glycan biosynthesis defects: A review. Clin. Chem.
- Wu CP, Bi YJ, Liu DM, Wang LY (2019) Hsa-miR-375 promotes the progression of inflammatory bowel disease by upregulating TLR4. Eur Rev Med Pharmacol Sci. https://doi.org/10.26355/eurrev_201909_18871
- Yao X, Zhang Y, Wu L, et al (2019) Immunohistochemical Study of NR2C2, BTG2, TBX19, and CDK2 Expression in 31 Paired Primary/Recurrent Nonfunctioning Pituitary Adenomas. Int J Endocrinol. https://doi.org/10.1155/2019/5731639
- Zhang C, Lu J, Liu B, et al (2016) Primate-specific miR-603 is implicated in the risk and pathogenesis of Alzheimer’s disease. Aging (Albany NY). https://doi.org/10.18632/aging.100887
There are 42 citations in total.
Details
| Primary Language | English |
|---|---|
| Subjects | Engineering |
| Journal Section | Research Article |
| Authors | |
| Publication Date | June 1, 2021 |
| Submission Date | September 27, 2020 |
| Acceptance Date | February 20, 2021 |
| Published in Issue | Year 2021 Volume: 9 Issue: 2 |
