Tan Yiyun, Liu Lei
Department of Spinal Surgery, Changsha Hospital of Traditional Chinese Medicine (Changsha Eighth Hospital), Changsha, Hunan 410000, P.R. China.
Department of Pain, Qianfo Shan Hospital, Jinan, Shandong 250014, P.R. China.
Exp Ther Med. 2019 Mar;17(3):2107-2112. doi: 10.3892/etm.2019.7180. Epub 2019 Jan 16.
Osteoporosis (OP) is a common metabolic bone disease with high incidence, and is recognized as a major public health problem worldwide. It is essential to clarify the pathogenesis of the disease for improving the diagnosis, prevention and treatment of OP. The aim of this study was to clarify the pivotal pathways and hub genes in OP using Gibbs sampling. The gene expression profile datasets were obtained from Gene Expression Omnibus (GEO) database. The pathways were enriched by Kyoto Encyclopedia of Genes and Genomes (KEGG) with genes intersection ≥5 based on gene expression profile data. Then, the acquired pathways were converted into Markov chains (MC). Gibbs sampling was conducted to obtain a new MC. In addition, the average probabilities of each pathway in two states containing human mesenchymal stem cells (hMSC) _middle-aged and hMSC_elderly were calculated through Markov chain Monte Carlo (MCMC) algorithm. Moreover, gene expression variation was taken into account to adjust the probability. Pivotal pathways were identified under adjusted posterior value >0.8. Then, Gibbs sampling was implemented to find hub genes from pathways. There were 280 pathways determined by the gene intersection ≥5. Gibbs sampling identified two disturbed pathways (pathways in cancer and influenza A) and two hub genes (cyclin A1 and WNT2) under the adjusted probability >0.8. Gene expression analysis showed that all the disturbed pathways and hub genes had increased expression levels in hMSC_middle-aged samples compared with hMSC_elderly samples. We identified two pivotal pathways and two hub genes in OP using Gibbs sampling. The results contribute to the understanding of underlying pathogenesis and could be considered as potential biomarkers for the therapy of OP.
骨质疏松症（OP）是一种常见的高发性代谢性骨病，被公认为是全球主要的公共卫生问题。明确该疾病的发病机制对于改善OP的诊断、预防和治疗至关重要。本研究的目的是使用吉布斯采样法阐明OP中的关键通路和核心基因。基因表达谱数据集从基因表达综合数据库（GEO）获得。基于基因表达谱数据，使用京都基因与基因组百科全书（KEGG）对基因交集≥5的通路进行富集。然后，将获得的通路转化为马尔可夫链（MC）。进行吉布斯采样以获得新的MC。此外，通过马尔可夫链蒙特卡罗（MCMC）算法计算包含人骨髓间充质干细胞（hMSC）_中年和hMSC_老年的两种状态下各通路的平均概率。此外，考虑基因表达变化来调整概率。在调整后的后验值>0.8时确定关键通路。然后，实施吉布斯采样以从通路中寻找核心基因。由基因交集≥5确定了280条通路。在调整后的概率>0.8时，吉布斯采样确定了两条受干扰的通路（癌症通路和甲型流感通路）和两个核心基因（细胞周期蛋白A1和WNT2）。基因表达分析表明，与hMSC_老年样本相比，所有受干扰的通路和核心基因在hMSC_中年样本中的表达水平均升高。我们使用吉布斯采样法在OP中确定了两条关键通路和两个核心基因。这些结果有助于理解潜在的发病机制，并可被视为OP治疗的潜在生物标志物。
