{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T19:38:59Z","timestamp":1740166739504,"version":"3.37.3"},"reference-count":85,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,1,14]],"date-time":"2021-01-14T00:00:00Z","timestamp":1610582400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2021,1,14]],"date-time":"2021-01-14T00:00:00Z","timestamp":1610582400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"funder":[{"DOI":"10.13039\/501100003447","name":"State Scholarships Foundation","doi-asserted-by":"crossref","award":["MIS-5033021"],"award-info":[{"award-number":["MIS-5033021"]}],"id":[{"id":"10.13039\/501100003447","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Netw Model Anal Health Inform Bioinforma"],"published-print":{"date-parts":[[2021,12]]},"DOI":"10.1007\/s13721-020-00278-z","type":"journal-article","created":{"date-parts":[[2021,1,14]],"date-time":"2021-01-14T11:03:17Z","timestamp":1610622197000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The human GPCR signal transduction network"],"prefix":"10.1007","volume":"10","author":[{"given":"Panagiota","family":"Kontou","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Athanasia","family":"Pavlopoulou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Niki","family":"Dimou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Margarita","family":"Theodoropoulou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georgia","family":"Braliou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georgios","family":"Tsaousis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georgios","family":"Pavlopoulos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stavros","family":"Hamodrakas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pantelis","family":"Bagos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,1,14]]},"reference":[{"issue":"9491","key":"278_CR1","doi-asserted-by":"publisher","first-page":"1059","DOI":"10.1016\/S0140-6736(05)67402-8","volume":"366","author":"KG Alberti","year":"2005","unstructured":"Alberti KG, Zimmet P, Shaw J, Group, I. D. F. E. T. F. C. (2005) The metabolic syndrome\u2014a new worldwide definition. Lancet 366(9491):1059\u20131062. https:\/\/doi.org\/10.1016\/S0140-6736(05)67402-8","journal-title":"Lancet"},{"issue":"Database issue","key":"278_CR2","doi-asserted-by":"publisher","first-page":"D789","DOI":"10.1093\/nar\/gku1205","volume":"43","author":"JS Amberger","year":"2015","unstructured":"Amberger JS, Bocchini CA, Schiettecatte F, Scott AF, Hamosh A (2015) OMIM.org: Online Mendelian Inheritance in Man (OMIM(R)), an online catalog of human genes and genetic disorders. Nucleic Acids Res 43(Database issue):D789-798. https:\/\/doi.org\/10.1093\/nar\/gku1205","journal-title":"Nucleic Acids Res"},{"issue":"2","key":"278_CR3","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1093\/protein\/7.2.195","volume":"7","author":"TK Attwood","year":"1994","unstructured":"Attwood TK, Findlay JB (1994) Fingerprinting G-protein-coupled receptors. Protein Eng 7(2):195\u2013203","journal-title":"Protein Eng"},{"key":"278_CR4","doi-asserted-by":"publisher","first-page":"435","DOI":"10.2119\/molmed.2014.00101","volume":"20","author":"HH Bach","year":"2014","unstructured":"Bach HH, Wong YM, Tripathi A, Nevins AM, Gamelli RL, Volkman BF et al (2014) Chemokine (C-X-C motif) receptor 4 and atypical chemokine receptor 3 regulate vascular alpha(1)-adrenergic receptor function. Mol Med 20:435\u2013447. https:\/\/doi.org\/10.2119\/molmed.2014.00101","journal-title":"Mol Med"},{"issue":"5939","key":"278_CR5","doi-asserted-by":"publisher","first-page":"412","DOI":"10.1126\/science.1173299","volume":"325","author":"AL Barabasi","year":"2009","unstructured":"Barabasi AL (2009) Scale-free networks: a decade and beyond. Science 325(5939):412\u2013413. https:\/\/doi.org\/10.1126\/science.1173299","journal-title":"Science"},{"issue":"2","key":"278_CR6","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1038\/nrg1272","volume":"5","author":"AL Barabasi","year":"2004","unstructured":"Barabasi AL, Oltvai ZN (2004) Network biology: understanding the cell\u2019s functional organization. Nat Rev Genet 5(2):101\u2013113. https:\/\/doi.org\/10.1038\/nrg1272","journal-title":"Nat Rev Genet"},{"issue":"5","key":"278_CR7","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1038\/ng0504-431","volume":"36","author":"KG Becker","year":"2004","unstructured":"Becker KG, Barnes KC, Bright TJ, Wang SA (2004) The genetic association database. Nat Genet 36(5):431\u2013432. https:\/\/doi.org\/10.1038\/ng0504-431","journal-title":"Nat Genet"},{"issue":"5","key":"278_CR8","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1034\/j.1399-0004.2003.00148.x","volume":"64","author":"AV Benjafield","year":"2003","unstructured":"Benjafield AV, Katyk K, Morris BJ (2003) Association of EDNRA, but not WNK4 or FKBP1B, polymorphisms with essential hypertension. Clin Genet 64(5):433\u2013438","journal-title":"Clin Genet"},{"issue":"45","key":"278_CR9","doi-asserted-by":"publisher","first-page":"13328","DOI":"10.1021\/jp204843r","volume":"115","author":"S Bockenhauer","year":"2011","unstructured":"Bockenhauer S, Furstenberg A, Yao XJ, Kobilka BK, Moerner WE (2011) Conformational dynamics of single G protein-coupled receptors in solution. J Phys Chem B 115(45):13328\u201313338. https:\/\/doi.org\/10.1021\/jp204843r","journal-title":"J Phys Chem B"},{"key":"278_CR10","doi-asserted-by":"publisher","unstructured":"Butte AJ, Kohane IS (2000) Mutual information relevance networks: functional genomic clustering using pairwise entropy measurements. Pac Symp Biocomput, 418\u2013429. https:\/\/doi.org\/10.1142\/9789814447331_0040","DOI":"10.1142\/9789814447331_0040"},{"issue":"6","key":"278_CR11","doi-asserted-by":"publisher","first-page":"765","DOI":"10.1210\/er.2000-0026","volume":"24","author":"TM Cabrera-Vera","year":"2003","unstructured":"Cabrera-Vera TM, Vanhauwe J, Thomas TO, Medkova M, Preininger A, Mazzoni MR et al (2003) Insights into G protein structure, function, and regulation. Endocr Rev 24(6):765\u2013781. https:\/\/doi.org\/10.1210\/er.2000-0026","journal-title":"Endocr Rev"},{"issue":"4","key":"278_CR12","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1016\/0092-8674(93)90245-L","volume":"73","author":"BR Conklin","year":"1993","unstructured":"Conklin BR, Bourne HR (1993) Structural elements of G alpha subunits that interact with G beta gamma, receptors, and effectors. Cell 73(4):631\u2013641","journal-title":"Cell"},{"issue":"2","key":"278_CR13","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1038\/nrc2069","volume":"7","author":"RT Dorsam","year":"2007","unstructured":"Dorsam RT, Gutkind JS (2007) G-protein-coupled receptors and cancer. Nat Rev Cancer 7(2):79\u201394. https:\/\/doi.org\/10.1038\/nrc2069","journal-title":"Nat Rev Cancer"},{"issue":"1","key":"278_CR14","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1093\/oxfordjournals.molbev.a026239","volume":"17","author":"L Duret","year":"2000","unstructured":"Duret L, Mouchiroud D (2000) Determinants of substitution rates in mammalian genes: expression pattern affects selection intensity but not mutation rate. Mol Biol Evol 17(1):68\u201374","journal-title":"Mol Biol Evol"},{"issue":"25","key":"278_CR15","doi-asserted-by":"publisher","first-page":"14863","DOI":"10.1073\/pnas.95.25.14863","volume":"95","author":"MB Eisen","year":"1998","unstructured":"Eisen MB, Spellman PT, Brown PO, Botstein D (1998) Cluster analysis and display of genome-wide expression patterns. Proc Natl Acad Sci U S A 95(25):14863\u201314868","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"7","key":"278_CR16","doi-asserted-by":"publisher","first-page":"1575","DOI":"10.1093\/nar\/30.7.1575","volume":"30","author":"AJ Enright","year":"2002","unstructured":"Enright AJ, Van Dongen S, Ouzounis CA (2002) An efficient algorithm for large-scale detection of protein families. Nucleic Acids Res 30(7):1575\u20131584","journal-title":"Nucleic Acids Res"},{"issue":"2","key":"278_CR17","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1124\/pr.57.2.5","volume":"57","author":"SM Foord","year":"2005","unstructured":"Foord SM, Bonner TI, Neubig RR, Rosser EM, Pin JP, Davenport AP et al (2005) International Union of Pharmacology. XLVI. G protein-coupled receptor list. Pharmacol Rev 57(2):279\u2013288. https:\/\/doi.org\/10.1124\/pr.57.2.5","journal-title":"Pharmacol Rev"},{"issue":"1","key":"278_CR18","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1210\/edrv.21.1.0390","volume":"21","author":"U Gether","year":"2000","unstructured":"Gether U (2000) Uncovering molecular mechanisms involved in activation of G protein-coupled receptors. Endocr Rev 21(1):90\u2013113. https:\/\/doi.org\/10.1210\/edrv.21.1.0390","journal-title":"Endocr Rev"},{"issue":"21","key":"278_CR19","doi-asserted-by":"publisher","first-page":"8685","DOI":"10.1073\/pnas.0701361104","volume":"104","author":"KI Goh","year":"2007","unstructured":"Goh KI, Cusick ME, Valle D, Childs B, Vidal M, Barabasi AL (2007) The human disease network. Proc Natl Acad Sci U S A 104(21):8685\u20138690. https:\/\/doi.org\/10.1073\/pnas.0701361104","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"8","key":"278_CR20","doi-asserted-by":"publisher","first-page":"e6511","DOI":"10.1371\/journal.pone.0006511","volume":"4","author":"IP Gorlov","year":"2009","unstructured":"Gorlov IP, Gallick GE, Gorlova OY, Amos C, Logothetis CJ (2009) GWAS meets microarray: are the results of genome-wide association studies and gene-expression profiling consistent? Prostate cancer as an example. PLoS ONE 4(8):e6511. https:\/\/doi.org\/10.1371\/journal.pone.0006511","journal-title":"PLoS ONE"},{"issue":"Database issue","key":"278_CR21","doi-asserted-by":"publisher","first-page":"D1079","DOI":"10.1093\/nar\/gku1071","volume":"43","author":"KA Gray","year":"2015","unstructured":"Gray KA, Yates B, Seal RL, Wright MW, Bruford EA (2015) Genenames.org: the HGNC resources in 2015. Nucleic Acids Res 43(Database issue):D1079-1085. https:\/\/doi.org\/10.1093\/nar\/gku1071","journal-title":"Nucleic Acids Res"},{"issue":"9","key":"278_CR22","doi-asserted-by":"publisher","first-page":"e1002694","DOI":"10.1371\/journal.pcbi.1002694","volume":"8","author":"Y Guan","year":"2012","unstructured":"Guan Y, Gorenshteyn D, Burmeister M, Wong AK, Schimenti JC, Handel MA et al (2012) Tissue-specific functional networks for prioritizing phenotype and disease genes. PLoS Comput Biol 8(9):e1002694. https:\/\/doi.org\/10.1371\/journal.pcbi.1002694","journal-title":"PLoS Comput Biol"},{"issue":"suppl 1","key":"278_CR23","doi-asserted-by":"publisher","first-page":"D680","DOI":"10.1093\/nar\/gkn728","volume":"37","author":"AJ Harmar","year":"2009","unstructured":"Harmar AJ, Hills RA, Rosser EM, Jones M, Buneman OP, Dunbar DR et al (2009) IUPHAR-DB: the IUPHAR database of G protein-coupled receptors and ion channels. Nucleic Acids Res 37(suppl 1):D680\u2013D685","journal-title":"Nucleic Acids Res"},{"issue":"6761 Suppl","key":"278_CR24","doi-asserted-by":"publisher","first-page":"C47","DOI":"10.1038\/35011540","volume":"402","author":"LH Hartwell","year":"1999","unstructured":"Hartwell LH, Hopfield JJ, Leibler S, Murray AW (1999) From molecular to modular cell biology. Nature 402(6761 Suppl):C47-52. https:\/\/doi.org\/10.1038\/35011540","journal-title":"Nature"},{"issue":"11","key":"278_CR25","doi-asserted-by":"publisher","first-page":"1106","DOI":"10.1101\/gr.9.11.1106","volume":"9","author":"LJ Heyer","year":"1999","unstructured":"Heyer LJ, Kruglyak S, Yooseph S (1999) Exploring expression data: identification and analysis of coexpressed genes. Genome Res 9(11):1106\u20131115","journal-title":"Genome Res"},{"issue":"9","key":"278_CR26","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1038\/nrd892","volume":"1","author":"AL Hopkins","year":"2002","unstructured":"Hopkins AL, Groom CR (2002) The druggable genome. Nat Rev Drug Discov 1(9):727\u2013730. https:\/\/doi.org\/10.1038\/nrd892","journal-title":"Nat Rev Drug Discov"},{"issue":"D1","key":"278_CR27","doi-asserted-by":"publisher","first-page":"D422","DOI":"10.1093\/nar\/gkt1255","volume":"42","author":"V Isberg","year":"2013","unstructured":"Isberg V, Vroling B, van der Kant R, Li K, Vriend G, Gloriam D (2013) GPCRDB: an information system for G protein-coupled receptors. Nucleic Acids Res 42(D1):D422\u2013D425. https:\/\/doi.org\/10.1093\/nar\/gkt1255","journal-title":"Nucleic Acids Res"},{"issue":"D1","key":"278_CR28","doi-asserted-by":"publisher","first-page":"D356","DOI":"10.1093\/nar\/gkv1178","volume":"44","author":"V Isberg","year":"2016","unstructured":"Isberg V, Mordalski S, Munk C, Rataj K, Harps\u00f8e K, Hauser AS et al (2016) GPCRdb: an information system for G protein-coupled receptors. Nucleic Acids Res\u00a044(D1):D356-364. https:\/\/doi.org\/10.1093\/nar\/gkv1178","journal-title":"Nucleic Acids Res"},{"issue":"6804","key":"278_CR29","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1038\/35036627","volume":"407","author":"H Jeong","year":"2000","unstructured":"Jeong H, Tombor B, Albert R, Oltvai ZN, Barabasi AL (2000) The large-scale organization of metabolic networks. Nature 407(6804):651\u2013654. https:\/\/doi.org\/10.1038\/35036627","journal-title":"Nature"},{"issue":"6833","key":"278_CR30","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1038\/35075138","volume":"411","author":"H Jeong","year":"2001","unstructured":"Jeong H, Mason SP, Barabasi AL, Oltvai ZN (2001) Lethality and centrality in protein networks. Nature 411(6833):41\u201342. https:\/\/doi.org\/10.1038\/35075138","journal-title":"Nature"},{"key":"278_CR31","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1146\/annurev-pharmtox-032112-135923","volume":"53","author":"V Katritch","year":"2013","unstructured":"Katritch V, Cherezov V, Stevens RC (2013) Structure-function of the G-protein-coupled receptor superfamily. Annu Rev Pharmacol Toxicol 53:531","journal-title":"Annu Rev Pharmacol Toxicol"},{"issue":"1","key":"278_CR32","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1002\/humu.20638","volume":"29","author":"J Kazius","year":"2008","unstructured":"Kazius J, Wurdinger K, van Iterson M, Kok J, B\u00e4ck T, IJzerman AP (2008) GPCR NaVa database: natural variants in human G protein-coupled receptors. Hum Mutat 29(1):39\u201344","journal-title":"Hum Mutat"},{"issue":"1","key":"278_CR33","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1186\/s13029-014-0030-2","volume":"9","author":"BB Khomtchouk","year":"2014","unstructured":"Khomtchouk BB, Van Booven DJ, Wahlestedt C (2014) HeatmapGenerator: high performance RNAseq and microarray visualization software suite to examine differential gene expression levels using an R and C++ hybrid computational pipeline. Source Code Biol Med 9(1):30. https:\/\/doi.org\/10.1186\/s13029-014-0030-2","journal-title":"Source Code Biol Med"},{"issue":"5631","key":"278_CR34","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1126\/science.1083853","volume":"301","author":"N King","year":"2003","unstructured":"King N, Hittinger CT, Carroll SB (2003) Evolution of key cell signaling and adhesion protein families predates animal origins. Science 301(5631):361\u2013363. https:\/\/doi.org\/10.1126\/science.1083853","journal-title":"Science"},{"issue":"4","key":"278_CR35","doi-asserted-by":"publisher","first-page":"794","DOI":"10.1016\/j.bbamem.2006.10.021","volume":"1768","author":"BK Kobilka","year":"2007","unstructured":"Kobilka BK (2007) G protein coupled receptor structure and activation. Biochimica et Biophysica Acta (BBA)-Biomembranes 1768(4):794\u2013807","journal-title":"Biochimica et Biophysica Acta (BBA)-Biomembranes"},{"issue":"1","key":"278_CR36","first-page":"1","volume":"2","author":"LF Kolakowski Jr","year":"1994","unstructured":"Kolakowski LF Jr (1994) GCRDb: a G-protein-coupled receptor database. Recept Channels 2(1):1\u20137","journal-title":"Recept Channels"},{"key":"278_CR37","doi-asserted-by":"publisher","first-page":"1036","DOI":"10.1016\/j.dib.2016.07.022","volume":"8","author":"PI Kontou","year":"2016","unstructured":"Kontou PI, Pavlopoulou A, Dimou NL, Pavlopoulos G, Bagos PG (2016a) Data and programs in support of network analysis of genes and their association with diseases. Data Brief 8:1036\u20131039. https:\/\/doi.org\/10.1016\/j.dib.2016.07.022","journal-title":"Data Brief"},{"issue":"1","key":"278_CR38","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/j.gene.2016.05.044","volume":"590","author":"PI Kontou","year":"2016","unstructured":"Kontou PI, Pavlopoulou A, Dimou NL, Pavlopoulos GA, Bagos PG (2016b) Network analysis of genes and their association with diseases. Gene 590(1):68\u201378. https:\/\/doi.org\/10.1016\/j.gene.2016.05.044","journal-title":"Gene"},{"issue":"1","key":"278_CR39","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/j.pharmthera.2004.05.002","volume":"103","author":"K Kristiansen","year":"2004","unstructured":"Kristiansen K (2004) Molecular mechanisms of ligand binding, signaling, and regulation within the superfamily of G-protein-coupled receptors: molecular modeling and mutagenesis approaches to receptor structure and function. Pharmacol Ther 103(1):21\u201380. https:\/\/doi.org\/10.1016\/j.pharmthera.2004.05.002","journal-title":"Pharmacol Ther"},{"issue":"8","key":"278_CR40","doi-asserted-by":"publisher","first-page":"1184","DOI":"10.1093\/bioinformatics\/bts084","volume":"28","author":"M Krupp","year":"2012","unstructured":"Krupp M, Marquardt JU, Sahin U, Galle PR, Castle J, Teufel A (2012) RNA-Seq Atlas\u2013a reference database for gene expression profiling in normal tissue by next-generation sequencing. Bioinformatics 28(8):1184\u20131185. https:\/\/doi.org\/10.1093\/bioinformatics\/bts084","journal-title":"Bioinformatics"},{"issue":"3","key":"278_CR41","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1038\/nbt1295","volume":"25","author":"K Lage","year":"2007","unstructured":"Lage K, Karlberg EO, Storling ZM, Olason PI, Pedersen AG, Rigina O et al (2007) A human phenome-interactome network of protein complexes implicated in genetic disorders. Nat Biotechnol 25(3):309\u2013316. https:\/\/doi.org\/10.1038\/nbt1295","journal-title":"Nat Biotechnol"},{"issue":"Database issue","key":"278_CR42","doi-asserted-by":"publisher","first-page":"D1091","DOI":"10.1093\/nar\/gkt1068","volume":"42","author":"V Law","year":"2014","unstructured":"Law V, Knox C, Djoumbou Y, Jewison T, Guo AC, Liu Y et al (2014) DrugBank 4.0: shedding new light on drug metabolism. Nucleic Acids Res 42(Database issue):D1091\u2013D1097. https:\/\/doi.org\/10.1093\/nar\/gkt1068","journal-title":"Nucleic Acids Res"},{"issue":"4","key":"278_CR43","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1016\/S0092-8674(01)00241-0","volume":"104","author":"RP Lifton","year":"2001","unstructured":"Lifton RP, Gharavi AG, Geller DS (2001) Molecular mechanisms of human hypertension. Cell 104(4):545\u2013556","journal-title":"Cell"},{"issue":"1","key":"278_CR44","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1002\/gepi.20546","volume":"35","author":"AK Manning","year":"2011","unstructured":"Manning AK, LaValley M, Liu CT, Rice K, An P, Liu Y et al (2011) Meta-analysis of gene-environment interaction: joint estimation of SNP and SNP x environment regression coefficients. Genet Epidemiol 35(1):11\u201318. https:\/\/doi.org\/10.1002\/gepi.20546","journal-title":"Genet Epidemiol"},{"issue":"7","key":"278_CR45","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1016\/S0165-6147(00)01678-3","volume":"22","author":"MJ Marinissen","year":"2001","unstructured":"Marinissen MJ, Gutkind JS (2001) G-protein-coupled receptors and signaling networks: emerging paradigms. Trends Pharmacol Sci 22(7):368\u2013376","journal-title":"Trends Pharmacol Sci"},{"issue":"5","key":"278_CR46","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1007\/s00018-004-4462-3","volume":"62","author":"CR McCudden","year":"2005","unstructured":"McCudden CR, Hains MD, Kimple RJ, Siderovski DP, Willard FS (2005) G-protein signaling: back to the future. Cell Mol Life Sci 62(5):551\u2013577. https:\/\/doi.org\/10.1007\/s00018-004-4462-3","journal-title":"Cell Mol Life Sci"},{"key":"278_CR47","unstructured":"Melmed S, Polonsky KS, Larsen PR, Kronenberg HM (2015) Williams Textbook of Endocrinology\u00a0E-Book. Elsevier Health Sciences"},{"issue":"4 Suppl 2","key":"278_CR48","doi-asserted-by":"publisher","first-page":"S115","DOI":"10.1681\/ASN.2005121340","volume":"17","author":"C Menzaghi","year":"2006","unstructured":"Menzaghi C, Paroni G, De Bonis C, Soccio T, Marucci A, Bacci S et al (2006) The -318 C>G single-nucleotide polymorphism in GNAI2 gene promoter region impairs transcriptional activity through specific binding of Sp1 transcription factor and is associated with high blood pressure in Caucasians from Italy. J Am Soc Nephrol 17(4 Suppl 2):S115\u2013119. https:\/\/doi.org\/10.1681\/ASN.2005121340","journal-title":"J Am Soc Nephrol"},{"issue":"1\u20132","key":"278_CR49","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s11010-005-9010-9","volume":"296","author":"N Mitsuhashi","year":"2007","unstructured":"Mitsuhashi N, Wu GD, Zhu H, Kearns-Jonker M, Cramer DV, Starnes VA et al (2007) Rat chemokine CXCL11: structure, tissue distribution, function and expression in cardiac transplantation models. Mol Cell Biochem 296(1\u20132):1\u20139. https:\/\/doi.org\/10.1007\/s11010-005-9010-9","journal-title":"Mol Cell Biochem"},{"key":"278_CR50","doi-asserted-by":"publisher","first-page":"436","DOI":"10.1186\/1471-2105-12-436","volume":"12","author":"JH Morris","year":"2011","unstructured":"Morris JH, Apeltsin L, Newman AM, Baumbach J, Wittkop T, Su G et al (2011) clusterMaker: a multi-algorithm clustering plugin for Cytoscape. BMC Bioinf 12:436. https:\/\/doi.org\/10.1186\/1471-2105-12-436","journal-title":"BMC Bioinf"},{"issue":"14","key":"278_CR51","doi-asserted-by":"publisher","first-page":"2195","DOI":"10.1111\/bph.13509","volume":"173","author":"C Munk","year":"2016","unstructured":"Munk C, Isberg V, Mordalski S, Harps\u00f8e K, Rataj K, Hauser A et al (2016) GPCRdb: the G protein-coupled receptor database\u2013an introduction. Br J Pharmacol 173(14):2195\u2013207. https:\/\/doi.org\/10.1111\/bph.13509","journal-title":"Br J Pharmacol"},{"issue":"2","key":"278_CR52","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1016\/j.biosystems.2008.10.002","volume":"95","author":"JC Nacher","year":"2009","unstructured":"Nacher JC, Hayashida M, Akutsu T (2009) Emergence of scale-free distribution in protein-protein interaction networks based on random selection of interacting domain pairs. Biosystems 95(2):155\u2013159. https:\/\/doi.org\/10.1016\/j.biosystems.2008.10.002","journal-title":"Biosystems"},{"issue":"6","key":"278_CR53","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1038\/nsb0698-451","volume":"5","author":"E Nogales","year":"1998","unstructured":"Nogales E, Downing KH, Amos LA, Lowe J (1998) Tubulin and FtsZ form a distinct family of GTPases. Nat Struct Biol 5(6):451\u2013458","journal-title":"Nat Struct Biol"},{"issue":"7","key":"278_CR54","doi-asserted-by":"publisher","first-page":"1073","DOI":"10.1016\/0092-8674(92)90630-U","volume":"69","author":"R Nusse","year":"1992","unstructured":"Nusse R, Varmus HE (1992) Wnt genes. Cell 69(7):1073\u20131087","journal-title":"Cell"},{"issue":"12","key":"278_CR55","doi-asserted-by":"publisher","first-page":"2670","DOI":"10.1038\/emboj.2012.146","volume":"31","author":"R Nusse","year":"2012","unstructured":"Nusse R, Varmus H (2012) Three decades of Wnts: a personal perspective on how a scientific field developed. EMBO J 31(12):2670\u20132684. https:\/\/doi.org\/10.1038\/emboj.2012.146","journal-title":"EMBO J"},{"issue":"1","key":"278_CR56","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/0962-8924(92)90125-7","volume":"2","author":"BR Oakley","year":"1992","unstructured":"Oakley BR (1992) Gamma-tubulin: the microtubule organizer? Trends Cell Biol 2(1):1\u20135","journal-title":"Trends Cell Biol"},{"key":"278_CR57","doi-asserted-by":"publisher","first-page":"bau017","DOI":"10.1093\/database\/bau017","volume":"2014","author":"A Oellrich","year":"2014","unstructured":"Oellrich A, Sanger Mouse Genetics P, Smedley D (2014) Linking tissues to phenotypes using gene expression profiles. Database (Oxford) 2014:bau017. https:\/\/doi.org\/10.1093\/database\/bau017","journal-title":"Database (Oxford)"},{"issue":"Database issue","key":"278_CR58","doi-asserted-by":"publisher","first-page":"D907","DOI":"10.1093\/nar\/gkm948","volume":"36","author":"Y Okuno","year":"2008","unstructured":"Okuno Y, Tamon A, Yabuuchi H, Niijima S, Minowa Y, Tonomura K et al (2008) GLIDA: GPCR\u2013ligand database for chemical genomics drug discovery\u2013database and tools update. Nucleic Acids Res 36(Database issue):D907\u2013D912. https:\/\/doi.org\/10.1093\/nar\/gkm948","journal-title":"Nucleic Acids Res"},{"issue":"Database issue","key":"278_CR59","doi-asserted-by":"publisher","first-page":"D358","DOI":"10.1093\/nar\/gkt1115","volume":"42","author":"S Orchard","year":"2014","unstructured":"Orchard S, Ammari M, Aranda B, Breuza L, Briganti L, Broackes-Carter F et al (2014) The MIntAct project\u2013IntAct as a common curation platform for 11 molecular interaction databases. Nucleic Acids Res 42(Database issue):D358\u2013D363. https:\/\/doi.org\/10.1093\/nar\/gkt1115","journal-title":"Nucleic Acids Res"},{"issue":"1","key":"278_CR60","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/j.1399-0004.2006.00708.x","volume":"71","author":"M Oti","year":"2007","unstructured":"Oti M, Brunner HG (2007) The modular nature of genetic diseases. Clin Genet 71(1):1\u201311. https:\/\/doi.org\/10.1111\/j.1399-0004.2006.00708.x","journal-title":"Clin Genet"},{"issue":"12","key":"278_CR61","doi-asserted-by":"publisher","first-page":"993","DOI":"10.1038\/nrd2199","volume":"5","author":"JP Overington","year":"2006","unstructured":"Overington JP, Al-Lazikani B, Hopkins AL (2006) How many drug targets are there? Nat Rev Drug Discov 5(12):993\u2013996. https:\/\/doi.org\/10.1038\/nrd2199","journal-title":"Nat Rev Drug Discov"},{"issue":"4","key":"278_CR62","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1086\/513286","volume":"80","author":"G Pare","year":"2007","unstructured":"Pare G, Serre D, Brisson D, Anand SS, Montpetit A, Tremblay G et al (2007) Genetic analysis of 103 candidate genes for coronary artery disease and associated phenotypes in a founder population reveals a new association between endothelin-1 and high-density lipoprotein cholesterol. Am J Hum Genet 80(4):673\u2013682. https:\/\/doi.org\/10.1086\/513286","journal-title":"Am J Hum Genet"},{"key":"278_CR63","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1186\/1752-0509-2-104","volume":"2","author":"GA Pavlopoulos","year":"2008","unstructured":"Pavlopoulos GA, O\u2019Donoghue SI, Satagopam VP, Soldatos TG, Pafilis E, Schneider R (2008) Arena3D: visualization of biological networks in 3D. BMC Syst Biol 2:104. https:\/\/doi.org\/10.1186\/1752-0509-2-104","journal-title":"BMC Syst Biol"},{"issue":"9","key":"278_CR64","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1038\/nrm908","volume":"3","author":"KL Pierce","year":"2002","unstructured":"Pierce KL, Premont RT, Lefkowitz RJ (2002) Seven-transmembrane receptors. Nat Rev Mol Cell Biol 3(9):639\u2013650. https:\/\/doi.org\/10.1038\/nrm908","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"11","key":"278_CR65","doi-asserted-by":"publisher","first-page":"1059","DOI":"10.1096\/fasebj.9.11.7649405","volume":"9","author":"S Rens-Domiano","year":"1995","unstructured":"Rens-Domiano S, Hamm HE (1995) Structural and functional relationships of heterotrimeric G-proteins. FASEB J 9(11):1059\u20131066","journal-title":"FASEB J"},{"key":"278_CR66","doi-asserted-by":"publisher","first-page":"baq019","DOI":"10.1093\/database\/baq019","volume":"2010","author":"VP Satagopam","year":"2010","unstructured":"Satagopam VP, Theodoropoulou MC, Stampolakis CK, Pavlopoulos GA, Papandreou NC, Bagos PG et al (2010) GPCRs, G-proteins, effectors and their interactions: human-gpDB, a database employing visualization tools and data integration techniques. Database (Oxford) 2010:baq019. https:\/\/doi.org\/10.1093\/database\/baq019","journal-title":"Database (Oxford)"},{"issue":"2","key":"278_CR67","doi-asserted-by":"publisher","first-page":"116","DOI":"10.3109\/08037051.2011.622988","volume":"21","author":"J Savva","year":"2012","unstructured":"Savva J, Alfakih K, Galloway SL, Hall AS, West RM, Ball SG et al (2012) The alpha(2C)-Del322-325 adrenoceptor polymorphism and the occurrence of left ventricular hypertrophy in hypertensives. Blood Press 21(2):116\u2013121. https:\/\/doi.org\/10.3109\/08037051.2011.622988","journal-title":"Blood Press"},{"issue":"2","key":"278_CR68","doi-asserted-by":"publisher","first-page":"700","DOI":"10.1016\/j.bbamem.2013.07.011","volume":"1838","author":"V Sequeira","year":"2014","unstructured":"Sequeira V, Nijenkamp LL, Regan JA, van der Velden J (2014) The physiological role of cardiac cytoskeleton and its alterations in heart failure. Biochim Biophys Acta 1838(2):700\u2013722. https:\/\/doi.org\/10.1016\/j.bbamem.2013.07.011","journal-title":"Biochim Biophys Acta"},{"issue":"11","key":"278_CR69","doi-asserted-by":"publisher","first-page":"2498","DOI":"10.1101\/gr.1239303","volume":"13","author":"P Shannon","year":"2003","unstructured":"Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D et al (2003) Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res 13(11):2498\u20132504. https:\/\/doi.org\/10.1101\/gr.1239303","journal-title":"Genome Res"},{"issue":"16","key":"278_CR70","doi-asserted-by":"publisher","first-page":"2195","DOI":"10.4155\/fmc.15.138","volume":"7","author":"M Skwarczynska","year":"2015","unstructured":"Skwarczynska M, Ottmann C (2015) Protein-protein interactions as drug targets. Future Med Chem 7(16):2195\u20132219. https:\/\/doi.org\/10.4155\/fmc.15.138","journal-title":"Future Med Chem"},{"key":"278_CR71","doi-asserted-by":"publisher","first-page":"025","DOI":"10.1093\/database\/bat025","volume":"2013","author":"D Smedley","year":"2013","unstructured":"Smedley D, Oellrich A, Kohler S, Ruef B, Sanger Mouse Genetics P, Westerfield M et al (2013) PhenoDigm: analyzing curated annotations to associate animal models with human diseases. Database (Oxford) 2013:025. https:\/\/doi.org\/10.1093\/database\/bat025","journal-title":"Database (Oxford)"},{"issue":"D1","key":"278_CR72","doi-asserted-by":"publisher","first-page":"D1054","DOI":"10.1093\/nar\/gkv1037","volume":"44","author":"C Southan","year":"2016","unstructured":"Southan C, Sharman JL, Benson HE, Faccenda E, Pawson AJ, Alexander SP et al (2016) The IUPHAR\/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. Nucleic Acids Res 44(D1):D1054-1068. https:\/\/doi.org\/10.1093\/nar\/gkv1037","journal-title":"Nucleic Acids Res"},{"key":"278_CR73","unstructured":"StataCorp.2013. Stata Statistical Software: Release 13. In T. College Station (Ed.): StataCorp LP."},{"issue":"Database issue","key":"278_CR74","doi-asserted-by":"publisher","first-page":"D447","DOI":"10.1093\/nar\/gku1003","volume":"43","author":"D Szklarczyk","year":"2015","unstructured":"Szklarczyk D, Franceschini A, Wyder S, Forslund K, Heller D, Huerta-Cepas J et al (2015) STRING v10: protein-protein interaction networks, integrated over the tree of life. Nucleic Acids Res 43(Database issue):D447\u2013D452. https:\/\/doi.org\/10.1093\/nar\/gku1003","journal-title":"Nucleic Acids Res"},{"issue":"12","key":"278_CR75","doi-asserted-by":"publisher","first-page":"1471","DOI":"10.1093\/bioinformatics\/btn206","volume":"24","author":"MC Theodoropoulou","year":"2008","unstructured":"Theodoropoulou MC, Bagos PG, Spyropoulos IC, Hamodrakas SJ (2008) gpDB: a database of GPCRs, G-proteins, effectors and their interactions. Bioinformatics 24(12):1471\u20131472. https:\/\/doi.org\/10.1093\/bioinformatics\/btn206","journal-title":"Bioinformatics"},{"key":"278_CR76","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1007\/978-1-4939-0956-8_8","volume":"1175","author":"MD Thompson","year":"2014","unstructured":"Thompson MD, Hendy GN, Percy ME, Bichet DG, Cole DE (2014) G protein-coupled receptor mutations and human genetic disease. Methods Mol Biol 1175:153\u2013187. https:\/\/doi.org\/10.1007\/978-1-4939-0956-8_8","journal-title":"Methods Mol Biol"},{"issue":"8","key":"278_CR77","doi-asserted-by":"publisher","first-page":"1090","DOI":"10.2174\/092986712799320556","volume":"19","author":"B Trzaskowski","year":"2012","unstructured":"Trzaskowski B, Latek D, Yuan S, Ghoshdastider U, Debinski A, Filipek S (2012) Action of molecular switches in GPCRs\u2013theoretical and experimental studies. Curr Med Chem 19(8):1090\u20131109","journal-title":"Curr Med Chem"},{"issue":"Database issue","key":"278_CR78","doi-asserted-by":"publisher","first-page":"D204","DOI":"10.1093\/nar\/gku989","volume":"43","author":"C UniProt","year":"2015","unstructured":"UniProt C (2015) UniProt: a hub for protein information. Nucleic Acids Res 43(Database issue):D204\u2013D212. https:\/\/doi.org\/10.1093\/nar\/gku989","journal-title":"Nucleic Acids Res"},{"issue":"2","key":"278_CR79","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1038\/nrd4189","volume":"13","author":"HF Vischer","year":"2014","unstructured":"Vischer HF, Siderius M, Leurs R, Smit MJ (2014) Herpesvirus-encoded GPCRs: neglected players in inflammatory and proliferative diseases? Nat Rev Drug Discov 13(2):123\u2013139. https:\/\/doi.org\/10.1038\/nrd4189","journal-title":"Nat Rev Drug Discov"},{"issue":"Database issue","key":"278_CR80","doi-asserted-by":"publisher","first-page":"D1001","DOI":"10.1093\/nar\/gkt1229","volume":"42","author":"D Welter","year":"2014","unstructured":"Welter D, MacArthur J, Morales J, Burdett T, Hall P, Junkins H et al (2014) The NHGRI GWAS Catalog, a curated resource of SNP-trait associations. Nucleic Acids Res 42(Database issue):D1001\u2013D1006. https:\/\/doi.org\/10.1093\/nar\/gkt1229","journal-title":"Nucleic Acids Res"},{"issue":"4","key":"278_CR81","doi-asserted-by":"publisher","first-page":"1159","DOI":"10.1152\/physrev.00003.2005","volume":"85","author":"N Wettschureck","year":"2005","unstructured":"Wettschureck N, Offermanns S (2005) Mammalian G proteins and their cell type specific functions. Physiol Rev 85(4):1159\u20131204. https:\/\/doi.org\/10.1152\/physrev.00003.2005","journal-title":"Physiol Rev"},{"issue":"2","key":"278_CR82","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1016\/j.metabol.2012.07.008","volume":"62","author":"B Xi","year":"2013","unstructured":"Xi B, Shen Y, Reilly KH, Wang X, Mi J (2013) Recapitulation of four hypertension susceptibility genes (CSK, CYP17A1, MTHFR, and FGF5) in East Asians. Metabolism 62(2):196\u2013203. https:\/\/doi.org\/10.1016\/j.metabol.2012.07.008","journal-title":"Metabolism"},{"issue":"4","key":"278_CR83","doi-asserted-by":"publisher","first-page":"586","DOI":"10.1039\/c2mb25429h","volume":"9","author":"X Zhang","year":"2013","unstructured":"Zhang X, Eggert US (2013) Non-traditional roles of G protein-coupled receptors in basic cell biology. Mol Biosyst 9(4):586\u2013595. https:\/\/doi.org\/10.1039\/c2mb25429h","journal-title":"Mol Biosyst"},{"issue":"10","key":"278_CR84","doi-asserted-by":"publisher","first-page":"836","DOI":"10.14348\/molcells.2015.0263","volume":"38","author":"D Zhang","year":"2015","unstructured":"Zhang D, Zhao Q, Wu B (2015) Structural studies of G protein-coupled receptors. Mol Cells 38(10):836","journal-title":"Mol Cells"},{"issue":"6","key":"278_CR85","doi-asserted-by":"publisher","first-page":"R1822","DOI":"10.1152\/ajpregu.90625.2008","volume":"295","author":"Z Zuberi","year":"2008","unstructured":"Zuberi Z, Birnbaumer L, Tinker A (2008) The role of inhibitory heterotrimeric G proteins in the control of in vivo heart rate dynamics. Am J Physiol Regul Integr Comp Physiol 295(6):R1822-1830. https:\/\/doi.org\/10.1152\/ajpregu.90625.2008","journal-title":"Am J Physiol Regul Integr Comp Physiol"}],"container-title":["Network Modeling Analysis in Health Informatics and Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s13721-020-00278-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s13721-020-00278-z\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s13721-020-00278-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,9]],"date-time":"2021-12-09T08:15:21Z","timestamp":1639037721000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s13721-020-00278-z"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,14]]},"references-count":85,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["278"],"URL":"https:\/\/doi.org\/10.1007\/s13721-020-00278-z","relation":{},"ISSN":["2192-6662","2192-6670"],"issn-type":[{"type":"print","value":"2192-6662"},{"type":"electronic","value":"2192-6670"}],"subject":[],"published":{"date-parts":[[2021,1,14]]},"assertion":[{"value":"16 May 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 November 2020","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 December 2020","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 January 2021","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"The authors declare that there is no conflict of interest regarding the publication of this paper.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"3"}}