Integrative and comparative omic approaches to identify molecular signatures of rheumatoid arthritis
[ X ]
Tarih
2020
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Adana Alparslan Türkeş Bilim ve Teknoloji Üniversitesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Romatoid artrit (RA) sıklıkla kronik sinovyal inflamasyonun eklem yıkımına, kronik sakatlığa ve yaşam beklentisinin azalmasına neden olduğu görülür. RA'nın patogenezi tam olarak bilinmemektedir. Bu çalışmada, sinovyal doku ve makrofaj hücreleri, kan hücreleri, T hücreleri, ?CD4?^+ T hücreleri, ?CD8?^+ T hücreleri, doğal öldürücü T (NKT) hücreleri, doğal öldürücü (NK) hücreleri, nötrofiller ve monosit hücreleri dahil olmak üzere çeşitli gen ekspresyon verileri bütüncül bir bakış açısıyla analiz edilerek RA'daki moleküler hedefler ve imzalar belirlendi. Farklı olarak ifade edilen genler (DEG'ler), hastalıklı ve sağlıklı numunelerin karşılaştırılmasıyla her bir veri kümesinden tanımlandı. Daha sonra, RA'ya özgü protein-protein etkileşimi (PPI) ve hub proteinler tanımlandı. Moleküler imzalar, transkripsiyonel düzenleyiciler ve PPI 'in fiziksel etkileşimleri kullanılarak hipergeometrik olasılık yoğunluk fonksiyonunu kullanan bir istatistiksel test yoluyla belirlendi. RA'lı her dokunun raportör metabolitleri, genom ölçekli metabolik ağ ve DEG'ler kullanılarak belirlendi. Ortak hub proteinleri, yeni raportör biyomolekülleri (yani reseptör, transkripsiyon faktörleri ve miRNA'lar), veya daha fazla doku tipindeki metabolitler belirlendi. SOCS2 Cullin ailesi üyeleri CUL1 ve CUL3, HDAC ailesi üyeleri HDAC2, HDAC4, HDAC9, RAS üyeleri KRAS, HRAS ve NRAS, OCS aile üyeleri SOCS1 ve SOCS2, hub protein olarak, AR, FOXP3 ve GATA2, TFs olarak NADP, NADPH, muhabir biyomolekül olarak ADP, piruvat ve Asetil-CoA üyeleri belirlendi. Önemli olarak, miR-155-5p tüm dokularda ortak miRNA' dır. Bulgularımız, RA' nın moleküler mekanizmasinin anlaşılması için çok önemli bir kaynak olabilir ve ilaç hedefleri ve yeni tanı stratejilerinin geliştirilmesi olarak düşünülebilir. İlgili genler ve miRNA'lar deneysel çalışmalarla doğrulanmalıdır.
Rheumatoid arthritis (RA) frequently seen chronic synovial inflammation causing joint destruction, chronic disability, and reduced life expectancy. The pathogenesis of RA is not completely known. In this study, several gene expression data including synovial tissue and macrophages cells, blood cells, T cells, ?CD4?^+ T cells, ?CD8?^+ T cells, natural killer T (NKT) cells, natural killer (NK) cells, neutrophils, and monocyte cells were analyzed with a holistic perspective and the molecular targets and signatures in RA were determined. Differentially expressed genes (DEGs) were identified from each dataset by comparing diseased and healthy samples. Afterward, the RA-specific protein-protein interaction (PPI) and hub proteins were identified. Molecular signatures were determined through a statistical test employing the hypergeometric probability density function by using the physical interactions of transcriptional regulators and PPI. Reporter metabolites of each tissue with RA were determined by using genome-scale metabolic networks and DEGs. It was determined the common hub proteins, novel reporter biomolecules (i.e. receptor, transcription factors, and miRNAs), metabolites in two or more tissue types. It was identified SOCS2 Cullin family members CUL1 and CUL3, HDAC family members HDAC2, HDAC4, HDAC9, RAS members KRAS, HRAS and NRAS, OCS family members SOCS1 and SOCS2, as hub proteins, AR, FOXP3 and GATA2 as TFs, NADP^+ NADPH, ADP, pyruvate, and Acetyl-CoA members as a reporter biomolecule. Importantly, miR-155-5p is common miRNAs in all tissues. Our findings could be a crucial resource for the understanding of RA molecular mechanisms and may be considered as drug targets and development of novel diagnostic strategies. Corresponding genes and miRNAs should be validated via experimental studies.
Rheumatoid arthritis (RA) frequently seen chronic synovial inflammation causing joint destruction, chronic disability, and reduced life expectancy. The pathogenesis of RA is not completely known. In this study, several gene expression data including synovial tissue and macrophages cells, blood cells, T cells, ?CD4?^+ T cells, ?CD8?^+ T cells, natural killer T (NKT) cells, natural killer (NK) cells, neutrophils, and monocyte cells were analyzed with a holistic perspective and the molecular targets and signatures in RA were determined. Differentially expressed genes (DEGs) were identified from each dataset by comparing diseased and healthy samples. Afterward, the RA-specific protein-protein interaction (PPI) and hub proteins were identified. Molecular signatures were determined through a statistical test employing the hypergeometric probability density function by using the physical interactions of transcriptional regulators and PPI. Reporter metabolites of each tissue with RA were determined by using genome-scale metabolic networks and DEGs. It was determined the common hub proteins, novel reporter biomolecules (i.e. receptor, transcription factors, and miRNAs), metabolites in two or more tissue types. It was identified SOCS2 Cullin family members CUL1 and CUL3, HDAC family members HDAC2, HDAC4, HDAC9, RAS members KRAS, HRAS and NRAS, OCS family members SOCS1 and SOCS2, as hub proteins, AR, FOXP3 and GATA2 as TFs, NADP^+ NADPH, ADP, pyruvate, and Acetyl-CoA members as a reporter biomolecule. Importantly, miR-155-5p is common miRNAs in all tissues. Our findings could be a crucial resource for the understanding of RA molecular mechanisms and may be considered as drug targets and development of novel diagnostic strategies. Corresponding genes and miRNAs should be validated via experimental studies.
Açıklama
Fen Bilimleri Enstitüsü, Biyomühendislik Ana Bilim Dalı
Anahtar Kelimeler
Biyomühendislik, Bioengineering
