Screening pathways and hub genes involved in osteoclastogenesis by gene expression analysis of circulating monocytes based on Gibbs sampling.

Abstract

Differential expression pathways and hub genes in circulating monocytes from healthy Chinese women with high peak bone mass (PBM) vs. low PBM were explored using a Markov chain Monte Carlo (MCMC) algorithm. Human circulating monocytes transcription profiling (containing 14 samples with high PBM and 12 samples with low PBM) and KEGG pathways were all downloaded from the public database. Initial state of all the pathways were constructed and Gibbs sampling was performed to obtain a Markov chain and the posterior values of all the pathways were calculated. The probability (α) of occurrence of each pathway was calculated based on the posterior value and it was adjusted by taking gene expression variation into account. Pathways with αadj >0.8 were considered as differentially expressed pathways. Then, these steps were performed again on all the genes in the differentially expressed pathways to find the hub genes in the differential pathways. After Gibbs sampling, neuroactive ligand-receptor interaction (hsa04080) with αadj = 0.986 was screened out as the differentially expressed pathway. Analyzing the genes in this pathway, three genes (neurotensin, tachykinin receptor 3 and follicle-stimulating hormone receptor) with αadj >0.8 were identified as hub genes in circulating monocytes which may associate with osteoporosis development. One pathway and three genes which may possess close relationship with osteoporosis development were found in this study. These results provide insights into our understanding of the role of circulating monocytes in osteoporosis development.