title: Network-based proteomic analysis for postmenopausal osteoporosis in Caucasian females.
abstract: Menopause is one of the crucial physiological events during the life of a woman. Transition of menopause status is accompanied by increased risks of various health problems such as osteoporosis. Peripheral blood monocytes can differentiate into osteoclasts and produce cytokines important for osteoclast activity. With quantitative proteomics LC-nano-ESI-MS(E) (where MS(E) is elevated-energy MS), we performed protein expression profiling of peripheral blood monocytes in 42 postmenopausal women with discordant bone mineral density (BMD) levels. Traditional comparative analysis showed proteins encoded by four genes (LOC654188, PPIA, TAGLN2, YWHAB) and three genes (LMNB1, ANXA2P2, ANXA2) were significantly down- and upregulated, respectively, in extremely low- versus high-BMD subjects. To study functionally orchestrating groups of detected proteins in the form of networks, we performed weighted gene coexpression network analysis and gene set enrichment analysis. Weighted gene coexpression network analysis showed that the module including the annexin gene family was most significantly correlated with low BMD, and the lipid-binding related GO terms were enriched in this identified module. Gene set enrichment analysis revealed that two significantly enriched gene sets may be involved in postmenopausal BMD variation by regulating pro-inflammatory cytokines activities. To gain more insights into the proteomics data generated, we performed integrative analyses of the datasets available to us at the genome (DNA level), transcriptome (RNA level), and proteome levels jointly.
authors.affiliation: Center for Bioinformatics and Genomics, Department of Biostatistics and Bioinformatics, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, USA.
authors.forename: Lan
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Center for Bioinformatics and Genomics, Department of Biostatistics and Bioinformatics, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, USA.
authors.forename: Yao-Zhong
authors.initials: YZ
authors.lastname: Liu
authors.affiliation: Center for Bioinformatics and Genomics, Department of Biostatistics and Bioinformatics, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, USA.|College of Life Sciences and Bioengineering, Beijing Jiaotong University, Beijing, P. R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zeng
authors.affiliation: Center for Bioinformatics and Genomics, Department of Biostatistics and Bioinformatics, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhu
authors.affiliation: Center for Bioinformatics and Genomics, Department of Biostatistics and Bioinformatics, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, USA.
authors.forename: Ying-Chun
authors.initials: YC
authors.lastname: Zhao
authors.affiliation: Center for Bioinformatics and Genomics, Department of Biostatistics and Bioinformatics, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, USA.
authors.forename: Ji-Gang
authors.initials: JG
authors.lastname: Zhang
authors.affiliation: Center for Bioinformatics and Genomics, Department of Biostatistics and Bioinformatics, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, USA.
authors.forename: Jia-Qiang
authors.initials: JQ
authors.lastname: Zhu
authors.affiliation: Center for Bioinformatics and Genomics, Department of Biostatistics and Bioinformatics, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, USA.
authors.forename: Hao
authors.initials: H
authors.lastname: He
authors.affiliation: Center for Bioinformatics and Genomics, Department of Biostatistics and Bioinformatics, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Shen
authors.affiliation: Center for Bioinformatics and Genomics, Department of Biostatistics and Bioinformatics, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, USA.
authors.forename: Qing
authors.initials: Q
authors.lastname: Tian
authors.affiliation: Center for Bioinformatics and Genomics, Department of Biostatistics and Bioinformatics, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, USA.|Laboratory of Proteins and Proteomics, Department of Epidemiology, Soochow University School of Public Health, Suzhou, P. R. China.
authors.forename: Fei-Yan
authors.initials: FY
authors.lastname: Deng
authors.affiliation: Department of Basic Medical Sciences, School of Medicine, University of Missouri - Kansas City, MO, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Papasian
authors.affiliation: Center for Bioinformatics and Genomics, Department of Biostatistics and Bioinformatics, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, USA.|College of Life Sciences and Bioengineering, Beijing Jiaotong University, Beijing, P. R. China.
authors.forename: Hong-Wen
authors.initials: HW
authors.lastname: Deng
mesh_terms: D000368:Aged; D017302:Annexins / Q000235:genetics / Q000378:metabolism; D015519:Bone Density; D051347:CapZ Actin Capping Protein / Q000235:genetics / Q000378:metabolism; D005260:Female; D053263:Gene Regulatory Networks; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000473:pathology*; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D020641:Polymorphism, Single Nucleotide; D060066:Protein Interaction Maps; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D040901:Proteomics / Q000379:methods*; D021241:Spectrometry, Mass, Electrospray Ionization; D059467:Transcriptome; D025801:Ubiquitin / Q000235:genetics / Q000378:metabolism; D044465:White People
chemical_list: D017302:Annexins; C495842:CAPZA1 protein, human; D051347:CapZ Actin Capping Protein; D011506:Proteins; D025801:Ubiquitin
keywords: Bioinformatics; GSEA; LC-MS; Menopause; Peripheral blood monocyte; WGCNA