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Supplementary File 4. Literature-Based Gene Curation of the Largest Connected Component of Blue Module and Individual Associati Supplementary File 4. Literature-based gene curation of the largest connected component of blue module and individual association with cord blood vitamin D levels at birth and reduced risk of wheezing status at first year of life. ENTREZ Gene Name Node Betweenness Vitamin D Wheeze Asthma Literature evidence ID Degree association protect (P- association (P-value) value) prior evidence 10409 BASP1 brain abundant, membrane 5 15 0.029745986 0.0801 YES/Not Role in EMT formation: attached signal protein 1 clear MicroRNA-191, by promoting (Homo sapiens) the EMT and increasing CSC- like properties, is involved in neoplastic and metastatic properties of transformed human bronchial epithelial cells. 5330 PLCB2 phospholipase C, beta 2 11 123 0.048205168 0.0584 YES/Not Suppression of PLCbeta2 by clear endotoxin plays a role in the adenosine A(2A) receptor- mediated switch of macrophages from an inflammatory to an angiogenic phenotype. Grinberg S, Hasko G, Wu D, Leibovich SJ. Am J Pathol. 2009 Dec;175(6):2439-53. doi: 10.2353/ajpath.2009.090290. Epub 2009 Oct 22. 5777 PTPN6 protein tyrosine 14 0 0.04932246 0.0563 YES/Not A critical role of SHP-1 in phosphatase, non-receptor clear regulation of type 2 type 6 inflammation in the lung. Oh SY, Zheng T, Kim YK, Cohn L, Homer RJ, McKenzie AN, Zhu Z. Am J Respir Cell Mol Biol. 2009 May;40(5):568-74. doi: 10.1165/rcmb.2008-0225OC. Epub 2008 Oct 23. PMID: 18952567 Free PMC Article 80223 RAB11FIP1 RAB11 family interacting 1 0 0.013387486 0.0583 YES/Not Whole-genome analysis of protein 1 (class I) clear temporal gene expression during early transdifferentiation of human lung alveolar epithelial type 2 cells in vitro. Morales Johansson H, Newman DR, Sannes PL. PLoS One. 2014 Apr 1;9(4):e93413. doi: 10.1371/journal.pone.0093413. eCollection 2014. PMID: 24690998 6688 SPI1 Spi-1 proto-oncogene 7 0 0.038120053 0.2038 YES/Not Not directly. Functional clear polymorphism in ALOX15 results in increased allele- specific transcription in macrophages through binding of the transcription factor SPI1. Wittwer J, Marti-Jaun J, Hersberger M. Hum Mutat. 2006 Jan;27(1):78- 87. Erratum in: Hum Mutat. 2006 Apr;27(4):387. PMID: 16320347 201294 UNC13D protein unc-13 homolog D 2 0.012746568 0.1884 Yes--maybe Munc13-2-/- baseline secretion (Munc13-4) defect reveals source of oligomeric mucins in mouse airways. Zhu Y, Ehre C, Abdullah LH, Sheehan JK, Roy M, Evans CM, Dickey BF, Davis CW. J Physiol. 2008 Apr 1;586(7):1977-92. doi: 10.1113/jphysiol.2007.149310. Epub 2008 Feb 7. Munc13-2-/- baseline secretion defect reveals source of oligomeric mucins in mouse airways. Zhu Y1, Ehre C, Abdullah LH, Sheehan JK, Roy M, Evans CM, Dickey BF, Davis CW. 6310 ATXN1 ataxin 1 21 353 0.039334309 0.1171 Yes ATXN1 protein family and CIC regulate extracellular matrix remodeling and lung alveolarization. Lee Y, Fryer JD, Kang H, Crespo-Barreto J, Bowman AB, Gao Y, Kahle JJ, Hong JS, Kheradmand F, Orr HT, Finegold MJ, Zoghbi HY. 116496 FAM129A NIBAN 11 124 0.049383665 0.0253 Yes Gene expression profiling of laser microdissected airway smooth muscle tissue in asthma and atopy.Yick CY1, Sterk PJ. 8826 IQGAP1 IQ motif containing GTPase 11 40 0.048211867 0.0232 Yes IQGAP1-dependent scaffold activating protein 1 suppresses RhoA and inhibits airway smooth muscle contraction. Bhattacharya M, Sundaram A, Kudo M, Farmer J, Ganesan P, Khalifeh-Soltani A, Arjomandi M, Atabai K, Huang X, Sheppard D. 3716 JAK1 Janus kinase 1 12 0 0.025574821 0.00885 Yes J Allergy Clin Immunol. 2014 Apr;133(4):1162-74. doi: 10.1016/j.jaci.2013.10.036. Epub 2013 Dec 22. Janus kinase 1/3 signaling pathways are key initiators of TH2 differentiation and lung allergic responses. 4067 LYN LYN proto-oncogene, Src 27 24 0.042545603 0.0321 Yes Lyn regulates cytotoxicity in family tyrosine kinase respiratory epithelial cells challenged by cigarette smoke extracts. Wang W, Ye Y, Li J, Li X, Zhou X, Tan D, Jin Y, Wu E, Cui Q, Wu M. Curr Mol Med. 2014;14(5):663-72. PMID: 24894179 4853 NOTCH2 notch 2 13 30 0.033511042 0.112 Yes PLoS One. 2011;6(11):e27629. doi: 10.1371/journal.pone.0027629. Epub 2011 Nov 15. Interleukin-19: a constituent of the regulome that controls antigen presenting cells in the lungs and airway responses to microbial products. 5791 PTPRE protein tyrosine 9 37 0.025808474 0.0393 Yes Genes to diseases (G2D) phosphatase, receptor type, computational method to E identify asthma candidate genes. Tremblay K, Lemire M, Potvin C, Tremblay A, Hunninghake GM, Raby BA, Hudson TJ, Perez-Iratxeta C, Andrade- Navarro MA, Laprise C. PLoS One. 2008 Aug 6;3(8):e2907. doi: 10.1371/journal.pone.0002907. PMID: 18682798 Free PMC Article 5795 PTPRJ protein tyrosine 13 343 0.039287628 0.0203 Yes The phosphatase CD148 phosphatase, receptor type, J promotes airway ( aka CD148) hyperresponsiveness through SRC family kinases. J Clin Invest. 2013 May;123(5):2037- 48. doi: 10.1172/JCI66397. Epub 2013 Apr 1. 79890 RIN3 Ras and Rab interactor 3 3 0 0.003837356 0.0495 Yes COPD: Lancet Respir Med. 2014 Mar;2(3):214-25. doi: 10.1016/S2213- 2600(14)70002-5. Epub 2014 Feb 7. Risk loci for chronic obstructive pulmonary disease: a genome-wide association study and meta-analysis. Cho MH, McDonald ML, Zhou X, Mattheisen M, Castaldi PJ, Hersh CP, Demeo DL, Sylvia JS, Ziniti J, Laird NM, Lange C, Litonjua AA, Sparrow D, Casaburi R, Barr RG, Regan EA, Make BJ, Hokanson JE, Lutz S, Dudenkov TM, Farzadegan H, Hetmanski JB, Tal-Singer R, Lomas DA, Bakke P, Gulsvik A, Crapo JD, Silverman EK, Beaty TH; NETT Genetics, ICGN, ECLIPSE and COPDGene Investigators. Collaborators (276) 6793 STK10 serine/threonine kinase 10 9 150 0.044467278 0.0123 Yes J Investig Allergol Clin Immunol. 2011;21(5):378-88. Variations in the STK10 gene and possible associations with aspirin-intolerant asthma in a Korean population. Kim JH1, Park BL, Cheong HS, Pasaje CF, Bae JS, Park JS, Jang AS, Uh ST, Choi JS, Kim YH, Kim MK, Choi IS, Cho SH, Choi BW, Koh IS, Park CS, Shin HD. 7040 TGFB1 transforming growth factor, 2 0.034549561 0.0954 Yes 1α,25-dihydroxyvitamin D3 beta 1 acts via transforming growth factor-β to up-regulate expression of immunosuppressive CD73 on human CD4(+) Foxp3(-) T cells. Mann EH, Chambers ES, Chen YH, Richards DF, Hawrylowicz CM. Immunology. 2015 Nov;146(3):423-31. doi: 10.1111/imm.12519. Epub 2015 Sep 13. PMID: 26251265 Similar articles: The association between the C-509T and T869C polymorphisms of TGF-β1 gene and the risk of asthma: a meta-analysis. Che Z, Zhu X, Yao C, Liu Y, Chen Y, Cao J, Liang C, Lu Y. 7090 TLE3 transducin-like enhancer of 3 0 0.041811722 0.0506 Yes J Allergy Clin Immunol. 2014 split 3 Jan;133(1):248-55.e1-10. doi: 10.1016/j.jaci.2013.06.018. Epub 2013 Aug 6. Genome-wide association study of lung function phenotypes in a founder population. Yao TC1, Du G2, Han L2, Sun Y2, Hu D3, Yang JJ4, Mathias R5, Roth LA3, Rafaels N5, Thompson EE2, Loisel DA2, Anderson R2, Eng C3, Arruabarrena Orbegozo M2, Young M6, Klocksieben JM7, Anderson E8, Shanovich K8, Lester LA6, Williams LK9, Barnes KC5, Burchard EG10, Nicolae DL11, Abney M2, Ober C12. The members of this family function in the Notch signaling pathway that regulates determination of cell fate during development. Expression of this gene has been associated with a favorable outcome to chemotherapy with taxanes for ovarian carcinoma. 140803 TRPM6 transient receptor potential 4 56 0.0168823 0.284 Yes Decreased renal mRNA cation channel, subfamily M, expression of TRPM6 is member 6 associated with hypomagnesemia in C57BL/6 asthmatic mice. Jiang SP, Wu YM, Guo SE, Lv ZQ. Eur Rev Med Pharmacol Sci. 2010 Nov;14(11):935-40. 9844 ELMO1 engulfment and cell motility 11 10 0.04555684 0.1484 NO/Not Association between Gαi2 and 1 clear ELMO1/Dock180 connects chemokine signalling with Rac activation and metastasis. Nat Commun. 2013;4:1706. doi: 10.1038/ncomms2680. 3937 LCP2 lymphocyte cytosolic protein 15 0 0.030166249 0.0348 No/Not Quantitative reduction of the 2 (SH2 domain containing clear TCR adapter protein SLP-76 leukocyte protein of 76kDa) unbalances immunity and immune regulation. Siggs OM1, Miosge LA2, Daley SR2, Asquith K3, Foster PS3, Liston A4, Goodnow CC5. 493 ATP2B4 ATPase, Ca++ transporting, 9 130 0.008715419 0.00574 No None. The expression of plasma membrane 4 different isoforms and splice variants is regulated in a developmental, tissue- and cell type-specific manner, suggesting that these pumps are functionally adapted to the physiological needs of particular cells and tissues. This gene encodes the plasma membrane calcium ATPase isoform 4. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008] 1265 CNN2 calponin 2 2 8 0.045574692 0.0179 No None: breast cancer Interaction with Notch?? J Biol Chem. 2014 Jan 17;289(3):1617-28. doi: 10.1074/jbc.M113.498147. Epub 2013 Nov 27. Mechanoregulation of h2- calponin gene expression and the role of Notch signaling. Jiang WR1, Cady G, Hossain MM, Huang QQ, Wang X, Jin JP. 28988 DBNL drebrin-like 7 0 0.033256697 0.2476 No UNKN: cancer 8295 TRRAP transformation/transcription 10 0 0.00961589 0.149 No None: common component of domain-associated protein many histone acetyltransferase (HAT) complexes and plays a role in transcription and DNA repair by recruiting HAT complexes to chromatin.
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