Dataset Information

Identification of drug candidate for osteoporosis by computational bioinformatics analysis of gene expression profile.

ABSTRACT:

Background

Osteoporosis is a condition of bones that leads to an increased susceptibility to fracture and consequent painful morbidity. It has become a major issue of life quality worldwide. However, until now, the molecular mechanism of this disease is far from being clear.

Methods

In this study, we obtained the gene expression profile of osteoporosis and controls from Gene Expression Omnibus and identified differentially expressed genes (DEGs) using classical t-test method. Then, functional enrichment analyses were performed to identify the dysregulated Gene Ontology categories and dysfunctional pathways in osteoporosis patients compared to controls. Besides, the connectivity map was used to identify compounds that induced inverse gene changes to osteoporosis.

Results

A total of 5581 DEGs were identified. We found these DEGs were enriched in 9 pathways by pathway enrichment analysis, including focal adhesion and MAPK signaling pathway. Besides, sanguinarine was identified as a potential therapeutic drug candidate capable of targeting osteoporosis.

Conclusion

Although candidate agents identified by our approach may be premature for clinical trials, it is clearly a direction that warrants additional consideration.

SUBMITTER: Yu G

PROVIDER: S-EPMC3599344 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

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Publications

Identification of drug candidate for osteoporosis by computational bioinformatics analysis of gene expression profile.

Yu Guiyong G Wang Litao L Li Yazhou Y Ma Zhihong Z Li Yu Y

European journal of medical research 20130301

<h4>Background</h4>Osteoporosis is a condition of bones that leads to an increased susceptibility to fracture and consequent painful morbidity. It has become a major issue of life quality worldwide. However, until now, the molecular mechanism of this disease is far from being clear.<h4>Methods</h4>In this study, we obtained the gene expression profile of osteoporosis and controls from Gene Expression Omnibus and identified differentially expressed genes (DEGs) using classical t-test method. Then ...[more]

PMID: 23448234

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Project description:OBJECTIVES:In order to screen the altered gene expression profile in peripheral blood mononuclear cells of patients with osteoporosis, we performed an integrated analysis of the online microarray studies of osteoporosis. METHODS:We searched the Gene Expression Omnibus (GEO) database for microarray studies of peripheral blood mononuclear cells in patients with osteoporosis. Subsequently, we integrated gene expression data sets from multiple microarray studies to obtain differentially expressed genes (DEGs) between patients with osteoporosis and normal controls. Gene function analysis was performed to uncover the functions of identified DEGs. RESULTS:A total of three microarray studies were selected for integrated analysis. In all, 1125 genes were found to be signi?cantly differentially expressed between osteoporosis patients and normal controls, with 373 upregulated and 752 downregulated genes. Positive regulation of the cellular amino metabolic process (gene ontology (GO): 0033240, false discovery rate (FDR) = 1.00E + 00) was significantly enriched under the GO category for biological processes, while for molecular functions, flavin adenine dinucleotide binding (GO: 0050660, FDR = 3.66E-01) and androgen receptor binding (GO: 0050681, FDR = 6.35E-01) were significantly enriched. DEGs were enriched in many osteoporosis-related signalling pathways, including those of mitogen-activated protein kinase (MAPK) and calcium. Protein-protein interaction (PPI) network analysis showed that the significant hub proteins contained ubiquitin specific peptidase 9, X-linked (Degree = 99), ubiquitin specific peptidase 19 (Degree = 57) and ubiquitin conjugating enzyme E2 B (Degree = 57). CONCLUSION:Analysis of gene function of identified differentially expressed genes may expand our understanding of fundamental mechanisms leading to osteoporosis. Moreover, significantly enriched pathways, such as MAPK and calcium, may involve in osteoporosis through osteoblastic differentiation and bone formation.Cite this article: J. J. Li, B. Q. Wang, Q. Fei, Y. Yang, D. Li. Identification of candidate genes in osteoporosis by integrated microarray analysis. Bone Joint Res 2016;5:594-601. DOI: 10.1302/2046-3758.512.BJR-2016-0073.R1.

Project description:Postmenopausal osteoporosis (PMOP), as well as its associated increased risk for fragility fracture, is one of the most disabling consequences of aging in women. This present study aimed to identify candidate genes that involve pathogenesis of PMOP and the therapeutic mechanism of Liuweidihuang (LWDH) pills on PMOP. We integrated microarray datasets of PMOP derived from the Gene Expression Omnibus (GEO) to screen differentially expressed genes (DEGs) between PMOP and normal controls as well as patients with PMOP and patients after treatment of LWDH pills. GO and KEGG enrichment analysis for DEGs were performed. The shared DEGs, associated with both the pathogenesis of PMOP and the therapeutic mechanism of LWDH, were further analyzed by protein-protein interaction (PPI) network. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to verify the DEGs obtained by our integrated analysis. Compared with normal controls, 1732 DEGs in PMOP were obtained with p<0.05. According to the qRT-PCR results, expression of ATF2, FBXW7, RDX, and RBBP4 was consistent with that in our integrated analysis, generally. GO and KEGG enrichment analysis showed that those DEGs were significantly enriched in regulation of transcription, DNA-dependent, cytoplasm, protein binding, and MAPK signaling pathway. A total of 58 shared DEGs in PMOP versus normal control and in patients with PMOP versus patients after LWDH treatment were identified, which had opposite expression trend in these two comparisons. In the PPI network, CSNK2A1, ATF2, and FBXW7 were three hub proteins. Three genes including ATF2, FBXW7, and RDX were speculated to be therapeutic targets of LWDH for PMOP based on BATMAN-TCM database. We speculated that three genes of ATF2, FBXW7, and RDX may play crucial roles in both pathogenesis of PMOP and therapeutic mechanism of LWDH on PMOP. Our results may provide clues for the molecular pathogenesis of PMOP and offer new possibilities for treatment of PMOP.

Dataset Information

Identification of drug candidate for osteoporosis by computational bioinformatics analysis of gene expression profile.

Background

Methods

Results

Conclusion

Publications

Identification of drug candidate for osteoporosis by computational bioinformatics analysis of gene expression profile.

Similar Datasets

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