Localized gtex database and its potential applications in biomedical research

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Efficient analysis of large amounts of transcriptome data requires fast and easy access to raw gene expression data. In our work, we localized the available expression data of more than 50000 genes in 54 tissues from approximately 1000 individuals from the GTEx system and created an easy-to-use interface for accessing and selecting these data. Using the capabilities of the localized system, we selected seven genes with highly stable expression from the housekeeping genes, investigated the changes in the number and activity of mast cells in the tibial artery with aging, studied changes in the components of the intestinal barrier and the state of mucosal immunity in old age in connection with the increased incidence of ulcerative colitis after 60 years. These examples demonstrate the applicability of the localized GTEx database in various biomedical projects and applications.

作者简介

G. Churakov

Institute of Experimental Medicine; Saint Petersburg State Pediatric University

St. Petersburg, 197022 Russia; St. Petersburg, 194100 Russia

M. Belyakov

St. Petersburg State University

St. Petersburg, 199034 Russia

T. Sall

Institute of Experimental Medicine

St. Petersburg, 197022 Russia

S. Orlov

Institute of Experimental Medicine; St. Petersburg State University

Email: serge@iem.spb.ru
St. Petersburg, 197022 Russia; St. Petersburg, 199034 Russia

参考

  1. Lonsdale J., Thomas J., Salvatore M., Phillips R., Lo E., Shad S., Hasz R., Walters G., Garcia F., Young N., Foster B., Moser M., Karasik E., Gillard B., Ramsey K., Sullivan S., Bridge J., Magazine H., Syron J., Fleming J., Siminoff L., Traino H., Mosavel M., Barker L., Jewell S., Rohrer D., Maxim D., Filkins D., Harbach P., Cortadillo E., Berghuis B., Turner L., Hudson E., Feenstra K., Sobin L., Robb J., Branton R, Korzeniewski K., Shive C., Tabor D., Qi L., Groch K., Nampally S., Buia S., Zimmerman A., Smith A., Burges R., Robinson K., Valentino K., Bradbury D., Cosentino M., Diaz-Mayoral N., Kennedy M., Engel T., Williams P., Erickson K., Ardlie K., Winckler W., Getz G., DeLuca D., Daniel MacArthur D., Kellis M., Thomson A., Young T., Gelfand E., Donovan M., Grant G., Mash D., Marcus Y., Basile M., Liu J., Zhu J., Tu Z., Cox N.J., Nicolae D.L., Gamazon E.R, Kyung H., Konkashbaev A., Pritchard J., Stevens M., Flutre T., Wen X., Dermitzakis T., Lappalainen T., Guigo R., Monlong J., Sammeth M., Koller D., Battle A., Mostafavi S., McCarthy M., Rivas M., Maller J., Rusyn I., Nobel A., Wright F., Shabalin A., Feolo M., Sharopova N., Sturcke A., Paschal J., Anderson J.M., Wilder E.L., Derr L.K., Green E.D., Struewing J.P., Temple G., Volpi S., Boyer J.T., Thomson E.J., Guyer M.S., Ng C., Abdallah A., Colantuoni D., Insel T.R., Koester S.E., Little A.R., Bender P.K, Lehner T., Yao Y., Compton C.C, Vaught J.B, Sawyer S., Lockhart N.C., Demchok J., Moore H.F. (2013) The genotype-tissue expression (GTEx) project. Nat. Genet. 45(6), 580–585. https://doi.org/10.1038/ng.2653
  2. Jacob F., Guertler R., Naim S., Nixdorf S., Fedier A., Hacker N.F., Heinzelmann-Schwarz V. (2013) Careful selection of reference genes is required for reliable performance of RT-qPCR in human normal and cancer cell lines. PLoS One. 8(3), e59180. https://doi.org/10.1371/journal.pone.0059180
  3. Nevone A., Lattarulo F., Russo M., Panno G., Milani P., Basset M., Avanzini M.A., Merlini G., Palladini G., Nuvolone M. (2023) A strategy for the selection of RT-qPCR reference genes based on publicly available transcriptomic datasets. Biomedicines. 11(4), 1079. https://doi.org/10.3390/biomedicines11041079
  4. Gorji-Bahri G., Moradtabrizi N., Vakhshiteh F., Hashemi A. (2021) Validation of common reference genes stability in exosomal mRNA-isolated from liver and breast cancer cell lines. Cell Biol. Int. 45(5), 1098–1110. https://doi.org/10.1002/cbin.11556
  5. Molina C., Jacquet E., Ponien P., Muñoz-Guijosa C., Baczkó I., Maier L.S., Donzeau-Gouge P., Dobrev D., Fischmeister R., Garnier A. (2017) Identification of optimal reference genes for transcriptomic analyses in normal and diseased human heart. Cardiovasc. Res. 114(2), 247–258. https://doi.org/10.1093/cvr/cvx182
  6. Fowkes F.G.R., Rudan D., Rudan D., Aboyans V., Denenberg J.O., McDermott M.M., Norman P.E., Sampson U.K.A., Williams L.J., Mensah G.A., Criqui M.H. (2013) Comparison of global estimates of prevalence and risk factors for peripheral artery disease in 2000 and 2010: a systematic review and analysis. Lancet. 382(9901), 1329–1340. https://doi.org/10.1016/s0140-6736(13)61249-0
  7. Slysz J., Sinha A., DeBerge M., Singh S., Avgousti H., Lee I., Glinton K., Nagasaka R., Dalal P., Alexandria S., Wai C.M., Tellez R., Vescovo M., Sunderraj A., Wang X., Schipma M., Sisk R., Gulati R, Vallejo J., Saigusa R., Lloyd-Jones D.M., Lomasney J., Weinberg S., Ho K., Ley K., Giannarelli C., Thorp E.B., Feinstein M.J. (2023) Single-cell profiling reveals inflammatory polarization of human carotid versus femoral plaque leukocytes. JCI Insight. 8(17), e171359. https://doi.org/10.1172/jci.insight.171359
  8. Elieh-Ali-Komi D., Bot I., Rodríguez-González M., Maurer M. (2024) Cellular and molecular mechanisms of mast cells in atherosclerotic plaque progression and destabilization. Clinic. Rev. Allerg. Immunol. 66(1), 30–49. https://doi.org/10.1007/s12016-024-08981-9
  9. Sovran B., Hugenholtz F., Elderman M., Van Beek A.A., Graversen K., Huijskes M., Boekschoten M.V., Savelkoul H.F.J., De Vos P., Dekker J., Wells J.M. (2019) Age-associated impairment of the mucus barrier function is associated with profound changes in microbiota and immunity. Sci. Rep. 9(1), 1437. https://doi.org/10.1038/s41598-018-35228-3
  10. Князев О.В., Шкурко Т.В., Каграманова А.В., Веселов А.В., Никонов Е.Л. (2020) Эпидемиология воспалительных заболеваний кишечника. Современное состояние проблемы (обзор литературы). Доказательная гастроэнтерология. 9(2), 66–73. https://doi.org/10.17116/dokgastro2020902166
  11. Holm S. (1979) A simple sequentially rejective multiple test procedure. Scandinavian J. Statistics. 6(2), 65–70. http://www.jstor.org/stable/4615733
  12. Ramel D., Gayral S., Sarthou M.K., Augé N., Nègre-Salvayre A., Laffargue M. (2019) Immune and smooth muscle cells interactions in atherosclerosis: how to target a breaking bad dialogue? Front. Pharmacol. 10, 1276. https://doi.org/10.3389/fphar.2019.01276
  13. Halova I., Draberova L., Draber P. (2012) Mast cell chemotaxis – chemoattractants and signaling pathways. Front. Immunol. 3, 119. https://doi.org/10.3389/fimmu.2012.00119
  14. Gonzalez-Quesada C., Frangogiannis N.G. (2009) Monocyte chemoattractant protein-1/CCL2 as a biomarker in acute coronary syndromes. Curr. Atheroscler. Rep. 11, 131–138. https://doi.org/10.1007/s11883-009-0021-y
  15. Inadera H., Egashira K., Takemoto M., Ouchi Y., Matsushima K. (1999) Increase in circulating levels of monocyte chemoattractant protein-1 with aging. J. Interferon Cytokine Res. 19(10), 1179–1182. https://doi.org/10.3389/fimmu.2012.00119
  16. Bais K., Kumari R., Prashar Y., Gill N.S. (2017) Review of various molecular targets on mast cells and its relation to obesity: a future perspective. Diabetes Metab. Syndr. 11(S2), S1001–S1007. https://doi.org/10.1016/j.dsx.2017.07.029
  17. Koelman L., Pivovarova-Ramich O., Pfeiffer A.F.H., Grune T., Aleksandrova K. (2019) Cytokines for evaluation of chronic inflammatory status in ageing research: reliability and phenotypic characterisation. Immun. Ageing. 16, 11. https://doi.org/10.1186/s12979-019-0151-1
  18. Marchini T., Mitre L.S., Wolf D. (2021) Inflammatory cell recruitment in cardiovascular disease. Front. Cell. Dev. Biol. 9, 635527. https://doi.org/10.3389/fcell.2021.635527
  19. Oldford S.A., Salsman S.P., Portales-Cervantes L., Alyazidi R., Anderson R., Haidl I.D., Marshall J.S. (2018) Interferon α2 and interferon γ induce the degranulation independent production of VEGF-A and IL-1 receptor antagonist and other mediators from human mast cells. Immun. Inflamm. Dis. 6(1), 176–189. https://doi.org/10.1002/iid3.211
  20. Золотова Н.А., Архиева Х.М., Зайратьянц О.В. (2019) Эпителиальный барьер толстой кишки в норме и при язвенном колите. Эксперим. и клин. гастроэнтерол. 162(2), 4–13. https://doi.org/10.31146/1682-8658-ecg-162-2-4-13
  21. Grondin J.A., Kwon Y.H., Far P.M., Haq S., Khan W.I. (2020) Mucins in intestinal mucosal defense and inflammation: learning from clinical and experimental studies. Front. Immunol. 11, 2054. https://doi.org/10.3389/fimmu.2020.02054
  22. Leoncini G., Cari L., Ronchetti S., Donato F., Caruso L., Calafà C., Villanacci V. (2024) Mucin expression profiles in ulcerative colitis: new insights on the histological mucosal healing. Int. J. Mol. Sci. 25(3), 1858. https://doi.org/10.3390/ijms25031858
  23. Sang X., Wang Q., Ning Y., Wang H., Zhang R., Li Y., Fang B., Lv C., Zhang Y., Wang X., Ren F. (2023) Age-related mucus barrier dysfunction in mice is related to the changes in Muc2 mucin in the colon. Nutrients. 15(8), 1830. https://doi.org/10.3390/nu15081830
  24. Baidoo N., Sanger G.J. (2024) Age-related decline in goblet cell numbers and mucin content of the human colon: implications for lower bowel functions in the elderly. Exp. Mol. Pathol. 139, 104923. https://doi.org/10.1016/j.yexmp.2024.104923
  25. Sheng Y.H., Triyana S., Wang R., Das I., Gerloff K., Florin T.H., Sutton P., McGuckin M.A. (2013) MUC1 and MUC13 differentially regulate epithelial inflammation in response to inflammatory and infectious stimuli. Mucosal Immunol. 6(3), 557–568. https://doi.org/10.1038/mi.2012.98
  26. Kononova S., Litvinova E., Vakhitov T., Skalinskay M., Sitkin S. (2021) Acceptive immunity: the role of fucosylated glycans in human host–microbiome interactions. Int. J. Mol. Sci. 22(8), 3854. https://doi.org/10.3390/ijms22083854
  27. Nason R., Büll C., Konstantinidi A., Sun L., Ye Z., Halim A., Du W., Sørensen D.M., Durbesson F., Furukawa S., Mandel U., Joshi H.J., Dworkin L.A., Hansen L., David L., Iverson T.M., Bensing B.A., Sullam P.M., Varki A., Vries E., de Haan C.A.M., Vincentelli R., Henrissat B., Vakhrushev S.Y., Clausen H., Narimatsu Y. (2021) Display of the human mucinome with defined O-glycans by gene engineered cells. Nat. Commun. 12(1), 4070. https://doi.org/10.1038/s41467-021-24366-4
  28. van der Post S., Jabbar K.S., Birchenough G., Arike L., Akhtar N., Sjovall H., Johansson M.E.V., Hansson G.C. (2019) Structural weakening of the colonic mucus barrier is an early event in ulcerative colitis pathogenesis. Gut. 68(12), 2142–2151. https://doi.org/10.1136/gutjnl-2018-317571
  29. Capaldo C.T., Farkas A.E., Hilgarth R.S., Krug S.M., Wolf M.F., Benedik J.K., Fromm M., Koval M., Parkos C., Nusrat A. (2014) Proinflammatory cytokine-induced tight junction remodeling through dynamic self-assembly of claudins. Mol. Biol. Cell. 25(18), 2710–2719. https://doi.org/10.1091/mbc.E14-02-0773
  30. Zhu L., Han J., Li L., Wang Y., Li Y., Zhang S. (2019) Claudin family participates in the pathogenesis of inflammatory bowel diseases and colitis-associated colorectal cancer. Front. Immunol. 10, 1441. https://doi.org/10.3389/fimmu.2019.01441
  31. Chen H., Sun H.M., Wu B., Sun T.Y., Han L.Z., Wang G., Shang Y.F., Yang S., Zhou D.S. (2023) Artesunate delays the dysfunction of age-related intestinal epithelial barrier by mitigating endoplasmic reticulum stress/unfolded protein response. Mech. Ageing Dev. 210, 111760. https://doi.org/10.1016/j.mad.2022.111760
  32. Tran L., Greenwood-Van Meerveld B. (2013) Age-associated remodeling of the intestinal epithelial barrier. J. Gerontol. A. Biol. Sci. Med. Sci. 68(9), 1045–1056. https://doi.org/10.1093/gerona/glt106
  33. Кононова С.В., Вахитов Т.Я., Кудрявцев И.В., Лазарева Н.М., Салль Т.С., Скалинская М.И., Бакулин И.Г., Хавкин А.И., Ситкин С.И. (2021) Цитокиновый профиль и иммунологический статус у пациентов с язвенным колитом. Вопр. практ. педиатрии. 16(6), 52–62. https://doi.org/10.20953/1817-7646-2021-6-52-62
  34. Landy J., Ronde E., English N., Clark S.K., Hart A.L., Knight S.C., Ciclitira P.J., Al-Hassi H.O. (2016) Tight junctions in inflammatory bowel diseases and inflammatory bowel disease associated colorectal cancer. W. J. Gastroenterol. 22(11), 3117–3126. https://doi.org/10.3748/wjg.v22.i11.3117
  35. Morsink M.A.J., Koch L.S., Hu S., Weersma R.K., van Goor H., Bourgonje A.R., Broersen K. (2024) Mucin-2 ER-to-Golgi transport mechanism identifies source of ER stress 1 in inflammatory bowel disease. Preprint. https://doi.org/10.1101/2024-05-13-593851
  36. Cornick S., Tawiah A., Chadee K. (2015) Roles and regulation of the mucus barrier in the gut. Tissue Barriers. 3(1–2), e982426. https://doi.org/10.4161/21688370-2014-982426
  37. Aspinall R. (2006) T cell development, ageing and Interleukin-7. Mech. Ageing Dev. 127(6), 572–578. https://doi.org/10.1016/j.mad.2006.01.016
  38. Watanabe M., Ueno Y., Yajima T., Iwao Y., Tsuchiya M., Ishikawa H., Aiso S., Hibi T., Ishii H. (1995) Interleukin 7 is produced by human intestinal epithelial cells and regulates the proliferation of intestinal mucosal lymphocytes. J. Clin. Invest. 95(6), 2945–2953. https://doi.org/10.1172/JCI118002
  39. Watanabe M., Ueno Y., Yamazaki M., Hibi T. (1999) Mucosal IL-7-mediated immune responses in chronic colitis-IL-7 transgenic mouse model. Immunol. Res. 20(3), 251–259. https://doi.org/10.1007/bf02790408
  40. Nguyen V., Mendelsohn A., Larrick J.W. (2017) Interleukin-7 and Immunosenescence. J. Immunol. Res. 2017, 4807853. https://doi.org/10.1155/2017/4807853
  41. Rios-Arce N.D., Collins F.L., Schepper J.D., Steury M.D., Raehtz S., Mallin H., Schoenherr D.T., Parameswaran N., McCabe L.R. (2017) Epithelial barrier function in gut-bone signaling. Adv. Exp. Med. Biol. 1033, 151–183. https://doi.org/10.1007/978-3-319-66653-2_8
  42. Zheng H., Zhang C., Wang Q., Feng S., Fang Y., Zhang S. (2022) The impact of aging on intestinal mucosal immune function and clinical applications. Front. Immunol. 13, 1029948. https://doi.org/10.3389/fimmu.2022.1029948
  43. Ihara S., Hirata Y., Koike K. (2017) TGF-β in inflammatory bowel disease: a key regulator of immune cells, epithelium, and the intestinal microbiota. J. Gastroenterol. 52(7), 777–787. https://doi.org/10.1007/s00535-017-1350-1
  44. Čužić S., Antolić M., Ognjenović A., Stupin-Polančec D., Petrinić Grba A., Hrvačić B., Dominis Kramarić M., Musladin S., Požgaj L., Zlatar I., Polančec D., Aralica G., Banić M., Urek M., Mijandrušić Sinčić B., Čubranić A., Glojnarić I., Bosnar M., Eraković Haber V. (2021) Claudins: beyond tight junctions in human IBD and murine models. Front. Pharmacol. 12, 682614. https://doi.org/10.3389/fphar.2021.682614
  45. Вахитов Т.Я., Кудрявцев И.В., Салль Т.С., Лазарева Н.М., Кононова С.В., Хавкин А.И., Ситкин С.И. (2020) Субпопуляции Т-хелперов, ключевые цитокины и хемокины в патогенезе воспалительных заболеваний кишечника (часть 1). Вопр. практ. педиатрии. 15(6), 67–78. https://doi.org/10.20953/1817-7646-2020-6-67-78
  46. Nian Y., Minami K., Maenesono R., Iske J., Yang J., Azuma H., ElKhal A., Tullius S.G. (2019) Changes of T-cell immunity over a lifetime. Transplantation. 103(11), 2227–2233. https://doi.org/10.1097/TP.0000000000002786
  47. Kanai T., Nemoto Y., Kamada N., Totsuka T., Hisamatsu T., Watanabe M., Hibi T. (2009) Homeostatic (IL-7) and effector (IL-17) cytokines as distinct but complementary target for an optimal therapeutic strategy in inflammatory bowel disease. Curr. Opin. Gastroenterol. 25(4), 306–313. https://doi.org/10.1097/MOG.0b013e32832bc627
  48. Tapping R.I., Omueti K.O., Johnson C.M. (2007). Genetic polymorphisms within the human Toll-like receptor 2 subfamily. Biochem. Soc. Transact. 35(6), 1445–1448. https://doi.org/10.1042/bst0351445
  49. Lu Y., Li X., Liu S., Zhang Y., Zhang D. (2018) Toll-like receptors and inflammatory bowel disease. Front. Immunol. 9, 72. https://doi.org/10.3389/fimmu.2018.00072
  50. Loh G., Blaut M. (2012) Role of gut commensal bacteria in inflammatory bowel diseases. Gut Microbes. 3(6), 544–555. https://doi.org/10.4161/gmic22156
  51. Kim H.J., Kim H., Lee J.H., Hwangbo C. (2023) Toll-like receptor 4 (TLR4): new insight immune and aging. Immun. Ageing. 20(1), 67. https://doi.org/101186/s12979-023-00383-3
  52. Вахитов Т.Я., Кудрявцев И.В., Салль Т.С., Лазарева Н.М., Кононова С.В., Хавкин А.И., Ситкин С.И. (2021) Субпопуляции Т-хелперов, ключевые цитокины и хемокины в патогенезе воспалительных заболеваний кишечника (часть 2). Вопр. практ. педиатрии. 16(1), 41–51. DOI: https://doi.org/10.20953/1817-7646-2021-1-41-51
  53. Malik J.A., Zafar M.A., Lamba T., Nanda S., Khan M.A., Agrewala J.N. (2023) The impact of aging-induced gut microbiome dysbiosis on dendritic cells and lung diseases. Gut Microbes. 15(2), 2290643. https://doi.org/10.1080/19490976.2023.2290643
  54. Enss M.L., Cornberg M., Wagner S., Gebert A., Henrichs M., Eisenblätter R., Beil W., Kownatzki R., Hedrich H.J. (2000) Proinflammatory cytokines trigger MUC gene expression and mucin release in the intestinal cancer cell line LS180. Inflamm Res. 49(4), 162–169. https://doi.org/10.1007/s000110050576
  55. Hasnain S.Z., Tauro S., Das I., Tong H., Chen A.C., Jeffery P.L., McDonald V., Florin T.H., McGuckin M.A. (2013) IL-10 promotes production of intestinal mucus by suppressing protein misfolding and endoplasmic reticulum stress in goblet cells. Gastroenterology. 144(2), 357–368. https://doi.org/10.1053/j.gastro.2012.10043
  56. Garcia-Hernandez V., Quiros M., Nusrat A. (2017) Intestinal epithelial claudins: expression and regulation in homeostasis and inflammation. Ann. N.Y. Acad. Sci. 1397(1), 66–79. https://doi.org/10.1111/nyas.13360
  57. Chen D., Tang T.X., Deng H., Yang X.P., Tang Z.H. (2021) Interleukin-7 biology and its effects on immune cells: mediator of generation, differentiation, survival, and homeostasis. Front. Immunol. 12, 747324. https://doi.org/10.3389/fimmu.2021.747324
  58. Kritikou E., Kuiper J., Kovanen P.T., Bot I. (2016) The impact of mast cells on cardiovascular diseases. Eur. J. Pharmacol. 778, 103–115. https://doi.org/10.1016/j.ejphar.2015.04.050
  59. Салль Т.С., Литвинова Е.А., Аржанова Е.Л., Кашина Т.А., Воронкина И.В., Кирик О.В., Ситкин С.И., Вахитов Т.Я. (2025) Сравнительный анализ основных факторов патогенеза воспалительных заболеваний кишечника в моделях in vitro и in vivo. Мед. акад. журн. 25(2). https://doi.org/10.17816/MAJ630556
  60. Sundin J., Öhman L., Simrén M. (2017) Understanding the gut microbiota in inflammatory and functional gastrointestinal diseases. Рsychosomatic Med. 79(8), 857–867. https://doi.org/10.1097/PSY.0000000000000470

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