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pmid:31261866
The Effects of Spaceflight Factors on the Human Plasma Proteome, Including Both Real Space Missions and Ground-Based Experiments.
Alexander G Brzhozovskiy · Alexey S Kononikhin · Lyudmila Ch Pastushkova · Daria N Kashirina · Maria I Indeykina · Igor A Popov · Marc-Antoine Custaud · Irina M Larina · Evgeny N Nikolaev
International journal of molecular sciences · 2019 doi:10.3390/ijms20133194
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Complete file
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LC-MS/MS-based proteomic analysis of blood plasma samples obtained from 13 cosmonauts before and after long-duration (169-199 days) missions on the International Space Station (ISS) and for five healthy men included in 21-day-long head-down bed rest (HDBR) and dry immersion experiments were performed. The semi-quantitative label-free analysis revealed significantly changed proteins: 19 proteins were significantly different on the first (+1) day after landing with respect to background levels; 44 proteins significantly changed during HDBR and 31 changed in the dry immersion experiment. Comparative analysis revealed nine common proteins (A1BG, A2M, SERPINA1, SERPINA3, SERPING1, SERPINC1, HP, CFB, TF), which changed their levels after landing, as well as in both ground-based experiments. Common processes, such as platelet degranulation, hemostasis, post-translational protein phosphorylation and processes of protein metabolism, indicate common pathogenesis in ground experiments and during spaceflight. Dissimilarity in the lists of significantly changed proteins could be explained by the differences in the dynamics of effective development in the ground-based experiments. Data are available via ProteomeXchange using the identifier PXD013305.", "claims": [{"id": "claim-method", "statement": "A two-sample Welch’s t-test with Benjamini–Hochberg correction was applied to identify the significantly changing proteins in the study groups (p-value < 0.01).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:31261866", "locator": "sections[11] \"3.3. 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Red/blue symbol—the increase/decrease of the protein level with respect to the background.", "rows": [["Protein IDs", "Gene Names", "Protein Names", "Unique Peptides", "p-Value", "t-Test Difference", "HDBR 21 Day", "Background"], ["Q9Y490", "TLN1", "Talin-1", "46", "8.4 × 10−6", "−4.6", "˅", "16.6 ± 0.6", "21.2 ± 1.8"], ["P01861", "IGHG4", "Ig gamma-4 chain C region", "3", "5.2 × 10−7", "−4.2", "˅", "18.5 ± 0.6", "22.6 ± 1.8"], ["P02655", "APOC2", "Apolipoprotein C-II;Proapolipoprotein C-II", "5", "9.9 × 10−6", "−3.6", "˅", "19.4 ± 1.2", "23.1 ± 1.2"], ["P12814", "ACTN1", "Alpha-actinin-1", "24", "1.2 × 10−6", "−3.3", "˅", "16.7 ± 0.5", "20 ± 2.3"], ["P01834", "IGKC", "Ig kappa chain C region", "5", "6.7 × 10−4", "−2.5", "˅", "19.3 ± 1.6", "21.8 ± 3"], ["P63261; P60709", "ACTG1; ACTB", "Actin. cytoplasmic 2; Actin. cytoplasmic 1", "6", "2.9 × 10−4", "−2.1", "˅", "18.4 ± 0.6", "20.6 ± 2.5"], ["O00187", "MASP2", "Mannan-binding lectin serine protease 2", "6", "1.5 × 10−5", "−1.9", "˅", "18.6 ± 1.1", "20.6 ± 1.1"], ["O00391", "QSOX1", "Sulfhydryl oxidase 1", "13", "1.3 × 10−4", "−1.4", "˅", "18.8 ± 0.6", "20.2 ± 1.4"], ["P55058", "PLTP", "Phospholipid transfer protein", "10", "1.6 × 10−6", "−1.4", "˅", "18.1 ± 0.4", "19.5 ± 0.8"], ["Q99878; Q96KK5; Q9BTM1; Q93077; Q8IUE6; Q7L7L0; P20671; P0C0S8; P04908; P16104", "HIST1H2AJ; HIST1H2AH; H2AFJ; HIST1H2AC; HIST2H2AB; HIST3H2A; HIST1H2AD; HIST1H2AG; HIST1H2AB; H2AFX", "Histone H2A", "1", "1.2 × 10−5", "−0.9", "˅", "17.2 ± 0.2", "18.2 ± 0.9"], ["P05154", "SERPINA5", "Plasma serine protease inhibitor", "9", "3.1 × 10−5", "0.7", "˄", "19.5 ± 0.2", "18.8 ± 0.5"], ["P07358", "C8B", "Complement component C8 beta chain", "12", "9.7 × 10−5", "0.8", "˄", "20.5 ± 0.5", "19.7 ± 1"], ["P03952", "KLKB1", "Plasma kallikrein", "9", "1.3 × 10−4", "0.9", "˄", "21.3 ± 0.6", "20.4 ± 1"], ["P01024", "C3", "Complement C3", "93", "5.1 × 10−5", "1.0", "˄", "27.2 ± 0.5", "26.2 ± 1.2"], ["P22792", "CPN2", "Carboxypeptidase N subunit 2", "6", "6.8 × 10−4", "1.1", "˄", "22 ± 0.6", "21 ± 0.7"], ["P04114", "APOB", "Apolipoprotein B-100", "192", "3.0 × 10−4", "1.1", "˄", "26.1 ± 0.3", "25.1 ± 1.7"], ["P06681", "C2", "Complement C2", "12", "2.6 × 10−4", "1.2", "˄", "21.1 ± 0.4", "19.9 ± 1.3"], ["P02766", "TTR", "Transthyretin", "10", "5.2 × 10−4", "1.2", "˄", "23.1 ± 0.9", "21.9 ± 1.7"], ["P25311", "AZGP1", "Zinc-alpha-2-glycoprotein", "13", "5.6 × 10−6", "1.4", "˄", "23 ± 0.6", "21.6 ± 1.2"], ["P02774", "GC", "Vitamin D-binding protein", "13", "8.6 × 10−6", "1.4", "˄", "23 ± 1", "21.6 ± 1.3"], ["P04196", "HRG", "Histidine-rich glycoprotein", "10", "6.7 × 10−7", "1.4", "˄", "23.5 ± 0.8", "22.1 ± 1"], ["Q06033", "ITIH3", "Inter-alpha-trypsin inhibitor heavy chain H3", "10", "6.4 × 10−7", "1.4", "˄", "20.9 ± 0.5", "19.5 ± 1.2"], ["P01019", "AGT", "Angiotensinogen", "10", "2.7 × 10−5", "1.4", "˄", "22 ± 1.1", "20.6 ± 1.3"], ["P08519", "LPA", "Apolipoprotein(a)", "7", "4.8 × 10−4", "1.5", "˄", "21.5 ± 1.3", "20 ± 0.9"], ["P01023", "A2M", "Alpha-2-macroglobulin", "36", "2.0 × 10−6", "1.5", "˄", "25.4 ± 0.6", "23.9 ± 1.6"], ["P01042", "KNG1", "Kininogen-1", "16", "1.1 × 10−7", "1.6", "˄", "23.1 ± 0.8", "21.5 ± 1.1"], ["O75882", "ATRN", "Attractin", "10", "5.0 × 10−4", "1.6", "˄", "21.3 ± 0.4", "19.7 ± 1.5"], ["P00751", "CFB", "Complement factor B", "18", "6.8 × 10−8", "1.7", "˄", "23.2 ± 0.5", "21.5 ± 1.2"], ["P35858", "IGFALS", "Insulin-like growth factor-binding protein complex acid labile subunit", "11", "7.9 × 10−5", "1.7", "˄", "20.9 ± 0.7", "19.2 ± 1.6"], ["P05546", "SERPIND1", "Heparin cofactor 2", "14", "1.3 × 10−8", "1.7", "˄", "22.6 ± 0.7", "20.9 ± 0.9"], ["P02750", "LRG1", "Leucine-rich alpha-2-glycoprotein", "8", "1.2 × 10−7", "1.8", "˄", "22.4 ± 0.4", "20.7 ± 1.2"], ["Q16610", "ECM1", "Extracellular matrix protein 1", "9", "1.7 × 10−4", "1.8", "˄", "20.7 ± 0.5", "18.9 ± 1.7"], ["Q14624", "ITIH4", "Inter-alpha-trypsin inhibitor heavy chain H4", "37", "3.2 × 10−9", "1.9", "˄", "25.1 ± 0.4", "23.2 ± 1.2"], ["P29622", "SERPINA4", "Kallistatin", "14", "5.0 × 10−7", "1.9", "˄", "21.5 ± 0.3", "19.5 ± 1.5"], ["P08697", "SERPINF2", "Alpha-2-antiplasmin", "16", "8.0 × 10−9", "2.0", "˄", "22.6 ± 0.5", "20.5 ± 1.4"], ["P01008", "SERPINC1", "Antithrombin-III", "22", "9.4 × 10−8", "2.1", "˄", "24.1 ± 0.8", "22 ± 1.6"], ["P04217", "A1BG", "Alpha-1B-glycoprotein", "12", "1.0 × 10−7", "2.1", "˄", "23.2 ± 0.9", "21.1 ± 1.5"], ["P01009", "SERPINA1", "Alpha-1-antitrypsin", "23", "4.9 × 10−8", "2.2", "˄", "24.9 ± 1.2", "22.7 ± 1.2"], ["P05155", "SERPING1", "Plasma protease C1 inhibitor", "14", "7.4 × 10−7", "2.3", "˄", "24 ± 1.3", "21.7 ± 1.8"], ["P01011", "SERPINA3", "Alpha-1-antichymotrypsin", "19", "1.6 × 10−9", "2.6", "˄", "24.9 ± 1", "22.2 ± 1.3"], ["P02790", "HPX", "Hemopexin", "14", "4.6 × 10−8", "2.7", "˄", "25.9 ± 1.3", "23.2 ± 1.8"], ["P19827", "ITIH1", "Inter-alpha-trypsin inhibitor heavy chain H1", "24", "4.1 × 10−9", "2.8", "˄", "24.6 ± 0.6", "21.8 ± 1.9"], ["P01031", "C5", "Complement C5", "34", "2.7 × 10−9", "3.2", "˄", "23.6 ± 0.3", "20.5 ± 1.9"], ["P19823", "ITIH2", "Inter-alpha-trypsin inhibitor heavy chain H2", "32", "7.3 × 10−10", "3.2", "˄", "25.6 ± 0.6", "22.4 ± 1.8"]], "row_count": 45, "column_count": 9, "numeric_cells": 283, "header_rows": 1, "locator": "section[4]/table-wrap[1]#ijms-20-03194-t001"}}, {"id": "asset:table:pmid:31261866:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:6b10dd8ca2374480f509adb0ca234b7d5e57f469008274bef876ea80a8b1f1b0", "bytes": 3755, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[5]/table-wrap[1]#ijms-20-03194-t002", "version": null, "note": "The list of proteins significantly changed (p < 0.01) on the 21st day of the dry immersion ground-based experiment with respect to their background levels (the day before the experiment). 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Red/blue symbol—the increase/decrease of protein level with respect to the background.", "rows": [["Protein IDs", "Gene Names", "Protein Names", "Unique Peptides", "p-Value", "t-Test Difference", "Immersion 21 Day", "Background"], ["P01024", "C3", "Complement C3", "93", "6.8 × 10−6", "1.0", "˄", "27.2 ± 0.5", "26.2 ± 1.2"], ["P02766", "TTR", "Transthyretin", "10", "1.3 × 10−5", "1.1", "˄", "23 ± 0.4", "21.9 ± 1.7"], ["P04114", "APOB", "Apolipoprotein B-100; Apolipoprotein B-48", "192", "4.7 × 10−7", "1.6", "˄", "25.4 ± 0.6", "24.2 ± 1.5"], ["O75636", "FCN3", "Ficolin-3", "10", "9.1 × 10−6", "1.7", "˄", "27.7 ± 1.1", "26.4 ± 1.4"], ["P00450", "CP", "Ceruloplasmin", "39", "5.6 × 10−6", "1.2", "˄", "23.7 ± 0.7", "22.3 ± 1.7"], ["P00734", "F2", "Prothrombin", "10", "3.1 × 10−5", "1.7", "˄", "21.5 ± 0.6", "20.1 ± 1.4"], ["P00736", "C1R", "Complement C1r subcomponent", "14", "7.5 × 10−6", "2.4", "˄", "26.6 ± 0.3", "25.1 ± 1.7"], ["P00738", "HP", "Haptoglobin", "7", "1.8 × 10−5", "1.9", "˄", "22.1 ± 0.7", "20.5 ± 2.1"], ["P01857", "IGHG1", "Ig gamma-1 chain C region", "4", "2.2 × 10−6", "2.6", "˄", "22.7 ± 0.4", "21 ± 2.1"], ["P01871; P04220", "IGHM", "Ig mu chain C region", "11", "4.3 × 10−6", "2.0", "˄", "24.7 ± 0.9", "22.9 ± 2.5"], ["P02647", "APOA1", "Apolipoprotein A-I", "28", "2.2 × 10−5", "1.3", "˄", "23.4 ± 0.7", "21.6 ± 2.2"], ["P02652", "APOA2", "Apolipoprotein A-II", "6", "1.2 × 10−6", "3.3", "˄", "25.4 ± 0.9", "23.6 ± 2.6"], ["P02671", "FGA", "Fibrinogen alpha chain", "48", "1.2 × 10−6", "2.9", "˄", "23.4 ± 0.6", "21.6 ± 2.1"], ["P02675", "FGB", "Fibrinogen beta chain", "26", "1.8 × 10−7", "3.3", "˄", "23.6 ± 0.9", "21.7 ± 2.5"], ["P02679", "FGG", "Fibrinogen gamma chain", "28", "2.4 × 10−7", "3.1", "˄", "21.5 ± 0.9", "19.6 ± 1.9"], ["P02747", "C1QC", "Complement C1q subcomponent subunit C", "5", "3.0 × 10−5", "1.3", "˄", "27.6 ± 0.7", "25.6 ± 2.1"], ["P02751", "FN1", "Fibronectin", "72", "1.3 × 10−7", "3.8", "˄", "24.9 ± 1", "22.9 ± 2.3"], ["P02760", "AMBP", "Protein AMBP", "5", "1.2 × 10−6", "1.4", "˄", "24.2 ± 0.9", "22.1 ± 2.3"], ["P02787", "TF", "Serotransferrin", "21", "1.8 × 10−6", "2.2", "˄", "25.1 ± 0.9", "22.9 ± 2.8"], ["P04004", "VTN", "Vitronectin", "15", "6.5 × 10−6", "2.1", "˄", "24.3 ± 1.1", "22.1 ± 2.1"], ["P06727", "APOA4", "Apolipoprotein A-IV", "34", "1.3 × 10−5", "1.8", "˄", "24.2 ± 1.2", "22 ± 2.6"], ["P07225", "PROS1", "Vitamin K-dependent protein S", "14", "1.9 × 10−6", "1.9", "˄", "22.4 ± 0.6", "20.2 ± 2.4"], ["P08603", "CFH", "Complement factor H", "18", "2.0 × 10−6", "2.1", "˄", "23.6 ± 1", "21.2 ± 2.9"], ["P09871", "C1S", "Complement C1s subcomponent", "17", "4.5 × 10−7", "2.6", "˄", "24.7 ± 0.8", "22 ± 2.7"], ["P0C0L5", "C4B", "Complement C4-B", "5", "7.1 × 10−7", "2.0", "˄", "25 ± 1.4", "22.3 ± 2.6"], ["P10909", "CLU", "Clusterin", "17", "9.1 × 10−7", "3.1", "˄", "28 ± 1.2", "25.1 ± 3.1"], ["P12259", "F5", "Coagulation factor V", "39", "1.4 × 10−5", "1.6", "˄", "27.8 ± 1.2", "24.6 ± 2.7"], ["P22352", "GPX3", "Glutathione peroxidase 3", "6", "2.3 × 10−6", "1.9", "˄", "25.8 ± 1.1", "22.7 ± 3.4"], ["P27169", "PON1", "Serum paraoxonase/arylesterase 1", "10", "5.0 × 10−6", "2.2", "˄", "24.9 ± 1.4", "21.6 ± 3.2"], ["P80108", "GPLD1", "Phosphatidylinositol-glycan-specific phospholipase D", "25", "1.5 × 10−5", "1.8", "˄", "28.2 ± 1", "24.9 ± 3.1"], ["Q96KN2", "CNDP1", "Beta-Ala-His dipeptidase", "18", "1.7 × 10−6", "2.2", "˄", "26.7 ± 0.5", "22.9 ± 3.7"]], "row_count": 32, "column_count": 9, "numeric_cells": 191, "header_rows": 1, "locator": "section[5]/table-wrap[1]#ijms-20-03194-t002"}}, {"id": "asset:table:pmid:31261866:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:07509fdf47688af898fd39b6d6c36595640b02a30e00a92f0e38df984594b5dd", "bytes": 2857, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[6]/table-wrap[1]#ijms-20-03194-t003", "version": null, "note": "The list of proteins significantly changed (p < 0.01) on +1 day after long-term spaceflight. Proteins were identified by pair-wise comparison (Welch’s t-test). Red/blue symbol—the increase/decrease of protein level with respect to the background.", "structure": {"pmcid": "PMC6651200", "section_index": 6, "section_title": "2.2. Spaceflight", "row_count": 20, "column_count": 10}, "table": {"label": "Table 3", "caption": "The list of proteins significantly changed (p < 0.01) on +1 day after long-term spaceflight. Proteins were identified by pair-wise comparison (Welch’s t-test). Red/blue symbol—the increase/decrease of protein level with respect to the background.", "rows": [["Protein IDs", "Gene Names", "Protein Names", "Unique Peptides", "p-Value", "t-Test Difference", "Log2 (LFQ Intensity) Background", "Log2 (LFQ Intensity) + 1 Day", "Log2 (LFQ Intensity) + 7 Days"], ["P02787", "TF", "Serotransferrin", "26", "1.70 × 10−7", "2.5", "˄", "20.7 ± 2.1", "23.2 ± 1.4", "21.5 ± 1.9"], ["P04217", "A1BG", "Alpha-1B-glycoprotein", "11", "3.30 × 10−5", "2.2", "˄", "17.1 ± 0.8", "19.3 ± 1.1", "18.3 ± 1.9"], ["P01008", "SERPINC1", "Antithrombin-III", "20", "3.60 × 10−8", "1.9", "˄", "19.1 ± 0.9", "20.9 ± 1.2", "19.6 ± 1.6"], ["P0DJI8", "SAA1", "Serum amyloid A-1 protein", "4", "8.40 × 10−5", "1.8", "˄", "19.6 ± 1.1", "21.4 ± 1.4", "20.2 ± 0.8"], ["P05155", "SERPING1", "Plasma protease C1 inhibitor", "11", "1.70 × 10−4", "1.8", "˄", "17.9 ± 1", "19.7 ± 1.4", "19.1 ± 1.4"], ["P00751", "CFB", "Complement factor B", "13", "9.50 × 10−6", "1.8", "˄", "18.1 ± 1.3", "19.9 ± 1.2", "18.7 ± 1.5"], ["P01011", "SERPINA3", "Alpha-1-antichymotrypsin", "20", "1.20 × 10−6", "1.7", "˄", "19.1 ± 1.1", "20.7 ± 1.1", "20.3 ± 0.9"], ["P01023", "A2M", "Alpha-2-macroglobulin", "40", "5.60 × 10−5", "1.4", "˄", "21.3 ± 1.8", "22.8 ± 1.4", "22.3 ± 1"], ["P01009", "SERPINA1", "Alpha-1-antitrypsin", "25", "2.30 × 10−6", "1.1", "˄", "21.2 ± 0.9", "22.4 ± 1.1", "21.9 ± 0.8"], ["P00738", "HP", "Haptoglobin", "7", "2.50 × 10−4", "1", "˄", "21.1 ± 0.7", "22.2 ± 1.4", "21.3 ± 1.1"], ["P21333", "FLNA", "Filamin-A", "11", "2.20 × 10−4", "−0.6", "˅", "19.5 ± 0.2", "18.9 ± 0.2", "19.1 ± 0"], ["Q15166", "PON3", "Serum paraoxonase/lactonase 3", "7", "6.80 × 10−4", "−0.6", "˅", "19.6 ± 0.4", "19 ± 0.7", "19.4 ± 0.6"], ["O00391", "QSOX1", "Sulfhydryl oxidase 1", "16", "1.50 × 10−4", "−0.7", "˅", "20.5 ± 0.6", "19.8 ± 0.8", "20.3 ± 0.6"], ["P12259", "F5", "Coagulation factor V", "26", "6.30 × 10−4", "−0.7", "˅", "21.1 ± 0.9", "20.4 ± 0.8", "20.9 ± 1"], ["P05160", "F13B", "Coagulation factor XIII B chain", "8", "3.30 × 10−4", "−0.8", "˅", "20.4 ± 0.9", "19.6 ± 0.7", "20 ± 0.9"], ["P33151", "CDH5", "Cadherin-5", "8", "4.70 × 10−4", "−0.8", "˅", "20 ± 0.4", "19.2 ± 0.9", "19.4 ± 0.7"], ["P00488", "F13A1", "Coagulation factor XIII A chain", "26", "3.70 × 10−5", "−0.8", "˅", "21.3 ± 0.8", "20.5 ± 0.8", "21 ± 0.9"], ["P12830", "CDH1", "Cadherin-1", "7", "2.10 × 10−4", "−0.8", "˅", "18.8 ± 0.6", "18 ± 0.4", "18.8 ± 0.4"], ["Q12805", "EFEMP1", "EGF-containing fibulin-like extracellular matrix protein 1", "5", "4.40 × 10−6", "−1.2", "˅", "19.4 ± 0.5", "18.1 ± 0.7", "19 ± 0.7"]], "row_count": 20, "column_count": 10, "numeric_cells": 146, "header_rows": 1, "locator": "section[6]/table-wrap[1]#ijms-20-03194-t003"}}], "gaps": ["asset:data:geo:PXD013305 not downloaded", "asset:data:geo:PXD013305 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "group_comparison", "specific": "welch_t_test", "label": "Group comparison", "dsl_operations": ["welch_t"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "A two-sample Welch’s t-test with Benjamini–Hochberg correction was applied to identify the significantly changing proteins in the study groups (p-value < 0.01)."}}], "targets": [], "gaps": []}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["welch_t"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: welch_t_test."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. 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