Abstract：Excess accumulation of lipids in the adipose tissue leads to obesity, which is associated with cardiovascular diseases, type Ⅱ diabetes and other pathologies. Adipogenesis is the process by which precursor stem cells differentiate into lipid laden adipocytes. Adipogenesis is regulated by a complex and highly orchestrated gene expression program. In order to discovery key regulatory genes and pathways in adipogenesis and explore the molecular regulation mechanism of adipogenesis, in the previous study, we constructed a Adipogenesis Regulation Network (ARN) Database (http://210.27.80.93/arn/) by mining over 9 000 papers related to adipogenesis, which contains more than 30 000 adipogenesis related data and information. In order to fully explore the potential value of ARN database to promote the study of adipogenesis, in this study, we designed an online analysis tool "ARN-analysis" to analyze the experimental data or to construct the scientific hypothesis about adipogenesis through two hypothesis construction processes: "open" and "closed". Furthermore, by count the number of the relation records, the number of the expression records and the number of the prediction records for each node (gene and micro RNA), the impact factor (IF) value which reflects the importance of each node was calculated. Finally, by analyzing and mapping the number of the relation records of nodes, the topology of the adipogenesis regulation network was explored. The results showed that the analysis tool of ARN database can effectively analyze 3 kinds of data: "node" and "expression" and "user input", it would be useful for researchers to analyze test data or build scientific hypotheses. Understanding of the regulation network topology can deepen our understanding of the mechanism of the formation of fat. In this study the analysis and prediction functions of ARN database was explored, ARN provided a new way for professional researchers to analyze data and construct hypotheses, explored the possibility of using a large number of scientific research data accumulated in the past to promote future research and practice.
[1]黄艳, 王力, 昝林森.数据库：重组和可视化成脂调控网络信息[J].计算生物学, 2016, 6(1):8-17
[2]Banerjee SS, Feinberg MW, Watanabe M, et al.The Krüppel-like factor KLF2 inhibits peroxisome proliferator-activated receptor-gamma expression and adipogenesis[J].J Biol Chem., 2003, 278(4):2581-2584
[3]Barth N, Langmann T, Sch?lmerich J, et al.Identification of regulatory elements in the human adipose most abundant gene transcript-1 ( apM-1) promoter: role of SP1SP3 and TNF-alpha as regulatory pathways[J].Diabetologia, 2002, Oct;45(10):1425-1433
[4]Chartoumpekis DV, Zaravinos A, Ziros PG, et al.Differential expression of miRNAss in adipose tissue after long-term high-fat diet-induced obesity in mice[J].PLoS One, 2012, 7(4):e34872-
[5]Chen YH, Yeh FL, Yeh SP, Ma HT, Hung SC, Hung MC, and Li LY.Myocyte enhancer factor-2 interacting transcriptional repressor (MITR) is a switch that promotes osteogenesis and inhibits adipogenesis of mesenchymal stem cells by inactivating peroxisome proliferator-activated receptor gamma-2[J].J Biol Chem, 2011, 286(12):10671-10680
[6]Chen J, Cui X, Shi C, et al.Differential lncRNA expression profiles in brown and white adipose tissues[J].Mol Genet Genomics, 2015, Apr;290(2):699-707
[7]Cho YW, Hong S, Jin Q, et al.Histone methylation regulator PTIP is required for PPARgamma and CEBPalpha expression and adipogenesis[J].Cell Metab, 2009, 10(1):27-39
[8]Deckmann K, R?rsch F, Steri R, et al.Dimethylcelecoxib inhibits mPGES-1 promoter activity by influencing EGR1 and NF-κB[J].Biochem Pharmacol, 2010, Nov 1;80(9):1365-1372
[9]Eijk CCvd, Mulligen EMv, Kors JA, et al..Constructing an Associative Concept Space for Literature-based Discovery[J][J].J Am Soc Inf Sci Technol, 2004, 55:436-444
[10]Fakhry M, Hamade E, Badran B, et al.Molecular mechanisms of mesenchymal stem cell differentiation towards osteoblasts[J].World J Stem Cells, 2013, 5(4):136-48
[11]Gao J, Liu YY, D'Souza RM, et al.Target control of complex networks[J].[J].Nat Commun, 2014, (5):5415-
[12]Gupta RK, Arany Z, Seale P, et al.Transcriptional control of preadipocyte determination by Zfp423[J].Nature, 2010, 464(7288):619-23
[13]Han H, Shim H, Shin D, et al.TRRUST: a reference database of human transcriptional regulatory interactions[J].[J].Sci Rep, 2015, (5):11432-
[14]Hu E, Kim JB, Sarraf P, et al.Inhibition of adipogenesis through MAP kinase-mediated phosphorylation of PPARgamma[J].Science, 1996, 274(5295):2100-3
[15]Jeong H, Tombor B, Albert R, et al.The large-scale organization of metabolic networks[J].Nature, 2000, 407(6804):651-4
[16]Jin Q, Wang C, Kuang X, et al.Gcn5 and PCAF regulate PPARγ and Prdm16 expression to facilitate brown adipogenesis[J].Mol Cell Biol, 2014, 34(19):3746-53
[17]Kim YJ, Hwang SJ, Bae YC, et al.MiR-21 regulates adipogenic differentiation through the modulation of TGF-beta signaling in mesenchymal stem cells derived from human adipose tissue[J].Stem Cells, 2009, 27(12):3093-102
[18]Kim SY, Kim AY, Lee HW, et al.miR-27a is a negative regulator of adipocyte differentiation via suppressing PPARgamma expression[J].Biochem Biophys Res Commun, 2010, 392(3):323-328
[19]Kozomara A, Griffiths-Jones S.miRBase: annotating high confidence miRNAss using deep sequencing data[J].[J].Nucleic Acids Res, 2014, (42):D68-D73
[20]Lee EK, Lee MJ, Abdelmohsen K, et al.miR-130 suppresses adipogenesis by inhibiting peroxisome proliferator-activated receptor gamma expression[J].Mol Cell Biol, 2011, 31(4):626-38
[21]Lee H, Kim HJ, Lee YJ, et al.Krüppel-like factor KLF8 plays a critical role in adipocyte differentiation[J].PLoS One, 2012, 7(12):e52474-
[22]Lemkul JA, Lewis SN, Bassaganya-Riera J, et al.Phosphorylation of PPARγ Affects the Collective Motions of the PPARγ-RXRα-DNA Complex[J].PLoS One, 2015, 10(5):e0123984-
[23]Li N, Muthusamy S, Liang R, et al.Increased expression of miR-34a and miR-93 in rat liver during aging, and their impact on the expression of Mgst1 and Sirt1[J]. [J].Mech Ageing, 2011, 132(3):75-78
[24]Liu X, Tamada K, Kishimoto R, et al.Transcriptome profiling of white adipose tissue in a mouse model for 15q duplication syndrome[J]. [J].Genom Data, 2015, (5):394-396
[25]Madonna S, Scarponi C, Sestito R, et al.The IFN-gamma-dependent suppressor of cytokine signaling 1 promoter activity is positively regulated by IFN regulatory factor-1 and Sp1 but repressed by growth factor independence-1b and Krüppel-like factor-4,and it is dysregulated in psoriatic keratinocytes[J].J Immunol, 2010, Aug 15;185(4):2467-81
[26]Mori T, Sakaue H, Iguchi H, et al.Role of Krüppel-like factor 15 (KLF15) in transcriptional regulation of adipogenesis[J].J Biol Chem, 2005, 280(13):12867-12875
[27]Pi J, Leung L, Xue P, et al.Deficiency in the nuclear factor E2-related factor-2 transcription factor results in impaired adipogenesis and protects against diet-induced obesity[J].J Biol Chem, 2010, 285(12):9292-300
[28]Portales-Casamar E, Arenillas D, Lim J, et al.PAZAR: a framework for collection and dissemination of cis-regulatory sequence annotation[J].[J].Nucleic Acids Res, 2009, 37(R207):1-12
[29]Qiang L, Wang L, Kon N, et al.Brown remodeling of white adipose tissue by SirT1-dependent deacetylation of Pparγ[J].Cell, 2012, 150(3):620-32
[30]Sarjeant K, Stephens JM.Adipogenesis[J][J].Cold Spring Harb Perspect Biol, 2012, (12):722-734
[31]Shore AM, Karamitri A, Kemp P, et al.Cold-induced changes in gene expression in brown adipose tissue,white adipose tissue and liver[J].PLoS One, 2013, Jul 22;8(7):e68933-
[32]Srinivasan P, Libbus B.Mining MEDLINE for Implicit Links between Dietary Substances and Diseases[J]. [J].Bioinformatics, 2004, 20(Suppl 1):i290-i296
[33]Stark C, Breitkreutz BJ, Reguly T, et al.BioGRID: a general repository for interaction datasets[J].Nucleic Acids Res, 2006, 34(Database issue):D535-9
[34]Sun L, Goff LA, Trapnell C, et al.Long noncoding RNAs regulate adipogenesis[J].Proc Natl Acad Sci U S A, 2013, Feb 26;110(9):3387-92
[35]Sun J, Wang Y, Li Y, et al.Downregulation of PPARγ by miR-548d-5p suppresses the adipogenic differentiation of human bone marrow mesenchymal stem cells and enhances their osteogenic potential[J]. [J].J Transl Med, 2014, (12):168-
[36]Swanson DR.A Second Example of Mutually Isolated Medical Literatures Related by Implicit, unnoticed Connections.[J].J Am Soc Inf Sci, 1989, (40):432-435
[37]Swanson DR.Complementary Structures in Disjoint Science Literatures.Proceedings of the 14th annual international ACM SIGIR conference on Research and development in information retrieval[M]..Illinois: ACM, 1991, :280-289
[38]Takada I, Kouzmenko AP, Kato S.Wnt and PPARgamma signaling in osteoblastogenesis and adipogenesis[J].Nat Rev Rheumatol, 2009, 5(8):442-7
[39]Tong Q, Dalgin G, Xu H, et al.Function of GATA transcription factors in preadipocyte-adipocyte transition[J].Science, 2000, 290(5489):134-8
[40]Weeber M.Klein H,de Jong-van den Berg L. T. W.,et al. Using concepts in literature-based discovery: simulating Swanson's Raynaud-fish oil and migraine-magnesium discoveries[J].Journal of the American Society for Information Science and Technology, 2001, 52(7):548-557
[41]Wren JD, Bekeredjian R, Stewart JA, et al.Knowledge Discovery by Automated Identification and Ranking of Implicit Relationships[J][J].Bioinformatics, 2004, 20:389-398
[42]Zhang JF, Fu WM, He ML, et al.MiRNA-20a promotes osteogenic differentiation of human mesenchymal stem cells by co-regulating BMP signaling[J].RNA Biol, 2011, 8(5):829-38
[43]Zhao Y, Zhang YD, Zhang YY, et al.p300-dependent acetylation of activating transcription factor 5 enhances CEBPβ transactivation of CEBPαduring 3T3-L1 differentiation[J].Mol Cell Biol, 2014, 34(3):315-24
