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Supplemental Information Supplemental Information IN VIVO LARGE SCALE MAPPING OF PROTEIN TURNOVER IN THE HUMAN CEREBROSPINAL FLUID Short title: protein turnover in the human cerebrospinal fluid Sylvain Lehmann1,2,*, Christophe Hirtz1,2, Jérôme Vialaret1, Maxence Ory3, Guillaume Gras Combes2,4, Marine Le Corre2,4, Stéphanie Badiou2,5, Jean-Paul Cristol2,5, Olivier Hanon6, Emmanuel Cornillot2,3, Luc Bauchet2,4, Audrey Gabelle2,7, Jacques Colinge2,3,8* (1) CHU de Montpellier, Montpellier, France ; IRMB, INSERM U1183, Laboratoire de Biochimie Protéomique Clinique, Montpellier, France. (2) Université de Montpellier, Montpellier, France. (3) Institut de Recherche en Cancérologie de Montpellier, INSERM U1194, Montpellier, France. (4) CHU de Montpellier, Hôpital Gui de Chauliac, Service de Neurochirurgie, Montpellier, France ; INSERM U1051, Montpellier, France. (5) Département de Biochimie et Hormonologie, CHU de Montpellier, Montpellier, France ; PhyMedExp, Université de Montpellier, INSERM, CNRS. (6) AP-HP, Hôpital Broca, Service de Gériatrie, Paris, France ; Université Paris Descartes, Sorbonne Paris Cité, Paris, France. (7) Centre Mémoire de Ressources et de Recherche Languedoc-Roussillon, Montpellier, France ; CHU de Montpellier, Hôpital Gui de Chauliac, Montpellier, France. (8) Institut régional du Cancer de Montpellier, Montpellier, France. (*) Co-corresponding authors ([email protected], [email protected]) Contents: A. Supplementary Tables B. Supplementary Figures C. Supplementary Proteomics Materials and Methods D. Supplementary Bioinformatics Materials and Methods E. Supplementary Data (in separated PDF files): 1. MRM parameters 2. HRMS Protein table 3. TQ Protein table 4. HRMS Protein model plots 5. TQ Protein model plots 6. Aligned TQ protein models 7. Original TQ protein models 8. mRNA expression in GTEx A. Supplementary Tables Table S1. Demographic information. Time after Initial CSF set up of CSF protein Patient Sex Age Diagnosis protein ventricular concentration concentration drainage Subarachnoid hemorrhage, Fisher scale P1 F 67 1.39 19 days 0.34 g/L 4, left carotid aneurysm Subarachnoid hemorrhage, Fisher scale P2 F 65 4, anterior communicating artery 1.97 15 days 0.15 g/L aneurysm Subarachnoid hemorrhage, Fisher scale P4 F 66 2.55 8 days 0.50 g/L 3, cerebral anterior artery aneurysm 13 Table S2. Free C6-Leu concentration in ventricular CSF and plasma. 13 Patient Fluid Time [h] C6-Leu concentration P1 CSF 0.00 0.000 CSF 3.02 0.072 CSF 9.22 0.080 CSF 12.30 0.035 CSF 15.22 0.016 CSF 18.13 0.012 CSF 21.13 0.010 CSF 24.47 0.008 Plasma 9.22 0.156 Plasma 24.47 0.006 P2 CSF 8.50 0.091 P4 CSF 8.67 0.099 Table S3. Skyline MS peak area export. Skyline export size, i.e. the number of peak areas, is reduced by a factor 2.6 after filtering but peptide and protein diversity is not affected. This means that redundant MS peaks – not the most intense isotopic peaks – were removed only. Skyline SCX Skyline Proteins Peptides filtered Proteins Peptides fraction export size export size F1 1,071,020 787 1,471 404,208 787 1,471 F2 1,101,124 646 1,451 426,704 646 1,451 F3 522,632 373 792 208,018 373 792 F4 349,312 195 409 124,316 195 409 Global* ∑=3,044,088 |ꓴ|=1,032 |ꓴ|=2,785 ∑=1,163,246 |ꓴ|=1,032 |ꓴ|=2,785 *Global numbers can be a sum (denoted by ∑=) or the size of the union of all the proteins or peptides in all the fractions (denoted by |ꓴ|=, a protein can have peptides in multiple fractions and a peptide can be detected in several fractions). Table S4. Turnover parameters for the 26 MRM targeted proteins. Empty cells reflect rejected observations that did not pass our quality filters (same criteria as for HRMS data). kc ± 2sd [1/h] Patient 1 Patient 2 Patient 4 HUGO symbol HRMS MRM MRM MRM A1BG 0.0077 ± 0.0011 0.0052 ± 0.0083 0.0069 ± 0.0096 A2M 0.0835 ± 0.0141 0.0840 ± 0.0276 0.0529 ± 0.0126 0.0822 ± 0.0374 ALB 0.0192 ± 0.0028 0.0064 ± 0.0025 0.0077 ± 0.0015 0.0078 ± 0.0032 AMBP 0.0809 ± 0.0149 0.0495 ± 0.0340 APOA1 0.0299 ± 0.0120 0.0098 ± 0.0039 0.0051 ± 0.0018 0.0107 ± 0.0044 APOA2 0.0175 ± 0.0080 0.0600 ± 0.0724 APOA4 0.0184 ± 0.0041 0.0226 ± 0.0554 APOD 0.0873 ± 0.0059 0.0862 ± 0.0233 0.0676 ± 0.0080 0.0893 ± 0.0311 APOE 0.0473 ± 0.0053 0.0554 ± 0.0208 0.0299 ± 0.0055 0.0440 ± 0.0264 B2M 0.0705 ± 0.0137 0.0646 ± 0.0077 0.0700 ± 0.0611 C3 0.0856 ± 0.0064 0.1140 ± 0.0420 C4B 0.0710 ± 0.0049 0.0622 ± 0.0227 0.0559 ± 0.0073 0.0502 ± 0.0290 C9 0.1179 ± 0.0250 0.0036 ± 0.0016 0.0126 ± 0.0063 0.0085 ± 0.0036 CFB 0.0843 ± 0.0090 0.0484 ± 0.0413 0.0803 ± 0.0392 CLU 0.1418 ± 0.0067 0.1559 ± 0.0353 0.1131 ± 0.0125 0.1342 ± 0.0341 CNDP1 0.0131 ± 0.0020 0.0237 ± 0.0100 CST3 0.0695 ± 0.0124 0.0661 ± 0.0232 0.0585 ± 0.0072 0.0574 ± 0.0276 F12 0.0076 ± 0.0030 0.0078 ± 0.0017 0.0071 ± 0.0048 GC 0.0238 ± 0.0128 0.0043 ± 0.0025 0.0294 ± 0.0149 0.0047 ± 0.0064 GSN 0.0719 ± 0.0093 0.0528 ± 0.0236 0.0548 ± 0.0091 0.0745 ± 0.0304 NRP2 0.0651 ± 0.0206 0.0604 ± 0.0064 0.0537 ± 0.0270 RBP4 0.0524 ± 0.0193 0.0275 ± 0.0226 0.0397 ± 0.0091 0.0326 ± 0.0631 SERPINA3 0.1038 ± 0.0060 0.0728 ± 0.0242 0.0560 ± 0.0078 0.0748 ± 0.0290 SERPINC1 0.0078 ± 0.0015 0.0923 ± 0.0190 SERPINF1 0.2182 ± 0.0089 0.1934 ± 0.0563 0.1695 ± 0.0211 0.1648 ± 0.0416 TTR 0.1856 ± 0.0619 0.2079 ± 0.0656 0.1637 ± 0.0193 0.1826 ± 0.0436 Table S5. List of 104 proteins directly involved in one or several diseases (see columns) as reported neXtProt medical tab (neXtProt 2018-09-03). gene protein name NX acc. code Disease Disease Disease name(s) Disintegrin and metalloprotein ADAM9 ase domain- NX_Q13443 Cone-rod dystrophy 9 (CORD9) containing protein 9 Angiotensinoge AGT NX_P01019 Essential hypertension (EHT) Renal tubular dysgenesis (RTD) n Alpha-2-HS- Alopecia-mental retardation AHSG NX_P02765 glycoprotein syndrome 1 (APMR1) Hyperthyroxinemia, familial ALB Serum albumin NX_P02768 Analbuminemia (ANALBA) dysalbuminemic (FDAH) Apolipoprotein High density lipoprotein High density lipoprotein Amyloidosis 8 APOA1 NX_P02647 A-I deficiency 2 (HDLD2) deficiency 1 (HDLD1) (AMYL8) Familial renal amyloidosis due Apolipoprotein APOA2 NX_P02652 to Apolipoprotein AII variant A-II 238269 Apolipoprotein Hypobetalipoproteinemia, Familial ligand-defective APOB NX_P04114 B-100 familial, 1 (FHBL1) apolipoprotein B-100 (FDB) Sea-blue Apolipoprotein APOE NX_P02649 Alzheimer disease 2 (AD2) Hyperlipoproteinemia 3 (HLPP3 histiocyte E disease (SBHD) Cerebral amyloid angiopathy, Amyloid-beta APP NX_P05067 Alzheimer disease 1 (AD1) APP-related (CAA-APP) A4 protein [MIM:605714 V-type proton ATP6AP1 ATPase subunit NX_Q15904 Immunodeficiency 47 (IMD47) S1 Parkinsonism with spasticity, X- Mental retardation, X-linked, ATP6AP2 Renin receptor NX_O75787 linked (XPDS) with epilepsy (MRXE) Beta-2- B2M NX_P61769 Amyloidosis 8 (AMYL8) Immunodeficiency 43 (IMD43) microglobulin Muscular dystrophy- Beta-1,4- dystroglycanopathy congenital B4GAT1 glucuronyltrans NX_O43505 Walker-Warburg syndrome 899 with brain and eye anomalies ferase 1 A13 (MDDGA13) Complement C1q Complement component C1q C1QA NX_P02745 subcomponent deficiency (C1QD) subunit A Complement C1q Complement component C1q C1QB NX_P02746 subcomponent deficiency (C1QD) subunit B Complement C1q Complement component C1q C1QC NX_P02747 subcomponent deficiency (C1QD) subunit C Complement Ehlers-Danlos syndrome, C1R C1r NX_P00736 periodontal type, 1 (EDSPD1) subcomponent Complement Complement component C1s Ehlers-Danlos syndrome, C1S C1s NX_P09871 deficiency (C1SD) periodontal type, 2 (EDSPD2) subcomponent Hemolytic uremic Macular degeneration, age- Complement component 3 C3 Complement C3 NX_P01024 syndrome related, 9 (ARMD9) deficiency (C3D) atypical 5 (AHUS5) Complement Complement component 4A Systemic lupus erythematosus C4A NX_P0C0L4 C4-A deficiency (C4AD) (SLE) Complement component 5 C5 Complement C5 NX_P01031 deficiency (C5D) Complement Complement component 6 C6 NX_P13671 component C6 deficiency (C6D) Complement Complement component 7 C7 NX_P10643 component C7 deficiency (C7D) Complement Complement component 8 C8A component C8 NX_P07357 deficiency, 1 (C8D1) alpha chain Complement Macular degeneration, age- Complement component 9 C9 NX_P02748 component C9 related, 15 (ARMD15) deficiency (C9D) Carbonic Osteopetrosis, autosomal CA2 NX_P00918 anhydrase 2 recessive 3 (OPTB3) Centrosomal Microcephaly 9, primary, CEP152 protein of 152 NX_O94986 Seckel syndrome 5 (SCKL5) autosomal recessive (MCPH9) kDa Centrosomal Leber congenital Senior-Loken syndrome 6 CEP290 protein of 290 NX_O15078 Joubert syndrome 5 (JBTS5) amaurosis 10 (SLSN6) kDa (LCA10) Age-related Complement Hemolytic uremic syndrome Complement factor B deficiency macular CFB NX_P00751 factor B atypical 4 (AHUS4) (CFBD) degeneration 279 Complement Complement factor D CFD NX_P00746 factor D deficiency (CFDD) Macular Complement Complement factor H deficiency degeneration, CFH NX_P08603 Basal laminar drusen (BLD) factor H (CFHD) age-related, 4 (ARMD4) Hemolytic uremic Complement Macular degeneration, age- Complement factor I deficiency CFI NX_P05156 syndrome factor I related, 13 (ARMD13 (CFI deficiency) atypical 3 (AHUS3) Chitinase-3-like CHI3L1 NX_P36222 Schizophrenia (SCZD) Asthma-related traits 7 (ASRT7) protein 1 Myopathy, congenital, CNTN1 Contactin-1 NX_Q12860 Compton-North (MYPCN) Collagen alpha- Ehlers-Danlos syndrome, classic Osteogenesis COL1A1 NX_P02452 Caffey disease (CAFFD) 1(I) chain type (EDS) and 7A imperfecta Ehlers-Danlos syndrome, Collagen alpha- COL1A2 NX_P08123 arthrochalasia type, 2 Osteogenesis imperfecta 2(I) chain (EDSARTH2) Collagen alpha- Ehlers-Danlos syndrome 3 COL3A1 NX_P02461 Familial aneurysm 1(III)
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