{"database":"MassIVE","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://massive-ftp.ucsd.edu/v06/MSV000092276/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"submitter":["Marialuisa Casella"],"full_dataset_link":["https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=78fca3bcbfa54f8784ea45ec4282c670"],"submitter_email":["marialuisa.casella@iss.it"],"sample_protocol":[""],"repository":["MassIVE"],"file_size":["608"],"ptm_modification":["UNIMOD:4 - \"Iodoacetamide derivative.\"","UNIMOD:35 - \"Oxidation or Hydroxylation.\""],"data_protocol":[""],"omics_type":["Proteomics"],"instrument_platform":["LTQ XL ETD"],"species":["Homo Sapiens (ncbitaxon:9606)"],"submitter_affiliation":["Istituto Superiore Sanita"],"name_synonyms":["Fresh, \"multiple sclerosis\" EXACT [NCI2004_11_17:C3243], Disseminated Sclerosis, other disease, Frozen Plasma, Exovesicles, Fresh Frozen Plasma, Activity, Apoptotic Body, Bodies, Blood, Sclerosis, Glt, EBR2A, Apoptotic Bodies, Multiple Sclerosis, disorders, MGLT1, Vesicles, GM-CSF, Extracellular Vesicle, spinal fluid, medical condition, MS (Multiple Sclerosis), Plasmas, Client, Vesicle, Frozen Plasmas, GLT1, B2T, MS, \"Multiple sclerosis\" EXACT [SNOMEDCT_2005_07_31:155023009], cerebral spinal fluid, diseases, Sargramostim, Apoptotic, Diseases, disease or disorder, liquor cerebrospinalis, \"Generalized multiple sclerosis (disorder)\" EXACT [SNOMEDCT_2005_07_31:192928003], condition, diseases and disorders, \"Multiple sclerosis\" EXACT [ICD9CM_2006:340], Exovesicle, GMCSF, Plasma, \"Multiple sclerosis (disorder)\" EXACT [SNOMEDCT_2005_07_31:24700007], \"Multiple sclerosis NOS (disorder)\" EXACT [SNOMEDCT_2005_07_31:192930001], Fresh Frozen Plasmas, Fresh Frozen, Blood Plasma, LAMB2T, human disease, 2900019G14Rik, BM600, portion of plasma, \"insular sclerosis\" EXACT [CSP2005:2042-2324], CSF, Colony-stimulating factor, Csfgm, 1700091C19Rik, Eaat2, Disseminated, Body, EBR2, Acute Fulminating, non-neoplastic, Multiple, disease, Molgramostin, generalised multiple sclerosis, GLT-1., Glt-1, Patient, Clients, Extracellular, Blood Plasmas, LAMNB2, Cerebral Spinal Fluid, disorder, Homo sapiens disease, AI159670, generalized multiple sclerosis, General activity, plasma"],"description_synonyms":["sodium salt, AU043776, ammonium formate, Protein Structure Database, 13C-labeled, MeCN, cadmium salt, Disorders, Surrogate Endpoints, ion, Laboratory, Dissociative Reactions, magnesium formate, Diagnosis, zinc salt, l(1)AA33, 5730420M11Rik, Protein Databases, Polypeptides, KL receptor activity, protein polypeptide chains, \"Multiple sclerosis\" EXACT [SNOMEDCT_2005_07_31:155023009], cerebral spinal fluid, cobalt(II) formate dihydrate, dorsal marginal zone, Biological, CH3-C#N, GRP1, Grp1, High Performance Liquid Chromatography, B1, symptoms, SCO5, 1, DGS, 2, SCO1, Software Engineering, 2-amino-3-mercaptopropanoic acid, Gsfsow3, WMS, Progression, Fresh Frozen, C, SET, Divorced, 2810441M03Rik, pore, nervous system disease or disorder, i2pp2a., M, PTPSTEP, beta-particle, Divorces, proteins, W, 3-((phenylacetyl)amino)-2, Fast, HPLC, AI047805, DmelCG4299, set, e, column, e-, l(1)B2/13.1, sample, D1, Chromatography, Bs, CT, High Speed Liquid, Sequence Databases, Half Cystine, z, plasma, DmAAF34715, Diagnose, Histological Labeling, nickel salt, GPH, SGS, LC-MS2, screening, Disseminated Sclerosis, l(1)LB9, Viral, cobalt (+2) salt, Zinc Cysteinate, Ct, Liquid Chromatography, not genetically inherited, Diagnoses, Software Tools, ACMICD, 6-dioxo-3-piperidinyl)benzeneacetamide, PBT, Sequence Database, Computer Applications, sodium (4:1:1) salt, Postmortem, magnesium salt, Dm1, disorder of nervous system, Recrudescence, Marker, Algorithm, Computer Applications Software, Fast Electron, Methionin, Hmet, (2R)-2-amino-3-sulfanylpropanoic acid, pbt, LAMB2T, Software Applications, HLA-DR-associated protein II, End Points, DI-2, CG11628, Source Software, I-2Dm, formate, signs, \"insular sclerosis\" EXACT [CSP2005:2042-2324], cromium (+3), Striatum-enriched protein-tyrosine phosphatase, Immunologic, Electron, MISS, Laboratory Marker, Cerebro, beta Trypsin, human, CG1106, beta(-), Protein Sequence, I-2PP1, Multiple, Applications, TAF-IBETA, liquid chromatography-tandem mass spectroscopy, Protein Database, ammonium (4:1) salt, DMZ, TAF-Ibeta, 3-(N-phenylacetylamino)-2, methyl cyanide, lead (+2) salt, Liquimeth, krk1, Computer Software Applications, \"multiple sclerosis\" EXACT [NCI2004_11_17:C3243], Fresh, l(1)VE614, 2-amino-4-(methylsulfanyl)butanoic acid, nickel formate dihydrate, GRP1/cytohesin 1, Fresh Frozen Plasma, lead formate, Apoptotic Body, Clinical Marker, Sclerosis, Multiple Sclerosis, aluminum salt, e(-), L-Zystein, GM-CSF, nervous system disease, precursor, NAT13P, thomson, protein-containing complex, Protein Structure Databases, CG7826, mass-to-charge ratio, Human, CG11633, neurological disease, LC-MSMS, Gene Products, CG7835, Cerebro Spinal, CG42273, Half-Cystine, Antemortem, nat13, \"Multiple sclerosis\" EXACT [ICD9CM_2006:340], Man, Application, \"Multiple sclerosis (disorder)\" EXACT [SNOMEDCT_2005_07_31:24700007], \"Multiple sclerosis NOS (disorder)\" EXACT [SNOMEDCT_2005_07_31:192930001], Open Source Softwares, Clinical, thallium (+1) salt, Recrudescences, nodus primitivus, Software Application, L Cysteine, E-920, Elektron, beta-Trypsin, rubidium salt, Dissociative Hysteria, Open Source Software, 2pp2a, Hcys, Diagnoses and Examinations, methanoic acid, ESI, ions, kf, man, High-Performance Liquid Chromatographies, CG10574, Computer Software Application, 2-amino-4-(methylthio)butanoic acid, 2PP2A, Clinical Course, Tools, CYSTEINE, Extracellular, dSET, dSet, FREE CYSTEINE, peptidos, UPLC, (2R)-2-amino-3-mercaptopropanoic acid, metionina, Biologic, PTHB1, LB5, disease remission, Electrons, SWISS-PROT, Antemortem Diagnoses, proto-oncogene c-Kit, findings, 1-(14)C-labeled, Dissociative, SwissProt, mak3, Serum Markers, Proteins, C14orf32, Fluids, stepk, Negatrons, 2310009E07Rik, spinal fluid, Stainings, potassium formate, MS (Multiple Sclerosis), copper (+2) salt, Rnt, acetonitrile, L-Isomer, buffer, Spinal Fluid, Immune Marker, Tool, Vesicle, lLB5, Amino Acid Sequence, Frozen Plasmas, polypeptide, Spinal Fluids, MS, Fluid, native protein, I-2PP2A, Surrogate End Point, KIT ligand receptor activity, C18, Hysterias, cupric formate, Dm I-2, MFS1, aluminum formate, Met, XKrk1, Biologic Markers, AU020952, lithium formate, ensemble, Surrogate, Separations, Endpoints, pore-forming toxin activity, (R)-2-amino-3-mercaptopropanoic acid, CSF, ethanenitrile, CD117, Disseminated, Body, 2-Amino-3-mercaptopropionic acid, DmelCG11628, beta, ME-IV, Computer Programs, Gene Proteins, High Pressure, Applications Softwares, C-Kit, Ssm, Dissociative Disorder, LAMNB2, xkl-1, liquid chromatography tandem mass spectrometry, E920, Mak3, Fugue, channel-forming toxin activity, Immune Markers, MAK3, liquid chromatography tandem mass spectroscopy, IPP2A2, Biological Markers, Viral Marker, WAP3, Antemortem Diagnosis, E 920, NCMe, Blood, leg, Biochemical, zinc formate, cleavage, Endpoint, atado, Protein Sequence Database, lead salt, Extracellular Vesicle, Xkl-1, protein, Serum, A10, Alkylations, Hysteria, peptide, Cut, B2T, Laboratory Markers, L-Isomer Methionine, relapse, Gsfsco1, ammonium tetraformate, Methionine, disease of nervous system, peptido, l(1)7Ba, l(1)7Bb, liquor cerebrospinalis, Min, Relapses, Cystein, 6-piperidinedione, protein aggregate, Gsfsco5, Computer Program, DmelCG42273, SOW3, A 10, Fresh Frozen Plasmas, LCMSMS, Man (Taxonomy), peptides, TAF-I, c14_5346, cisteina, Recurrences, Open, min, Computer Programs and Programming, mAPC, CG12352, copper, SCAN, CG11387, antineoplaston-A10, WFDC14, hNAT5, IGAAD, Immune, lithium salt, Markers, High-Performance, hSAN, DmelCG10574, RUN, Run, DmelCG1106, Viral Markers, l(2)k08110, Reaction, Therapies, Exacerbation, High-Performance Liquid, Sl, GPHYSD2, Racemethionine, ammonium (2:1) salt, disease or disorder of nervous system, Mak3p, Therapy, phapii, Relapse, Cerebro Spinal Fluid, Frozen Plasma, Surrogate Endpoint, NAT13, Modern, Disease Exacerbation, LC-MS/MS, 2-Amino-4-(methylthio)butyric acid, Dmel_CG7826, StF-IT-1, Tr-kit, Th, Labeling and Staining, Biochemical Markers, Positrons, Plasmas, Biologic Marker, Nat13, Cys, Source Softwares, AA33, neurological disorder, Acute onset, Programs, Cerebro Spinal Fluids, Menstruation, Program, Ionen, Examinations and Diagnoses, Apoptotic, 3.1.3.48, Computer Applications Softwares, kl1-A, \"Generalized multiple sclerosis (disorder)\" EXACT [SNOMEDCT_2005_07_31:192928003], Henson's node, neurological problem, Softwares, KIT, BcDNA:GH10590, Postmortem Diagnosis, nickel (+2) salt, Dmel_CG7835, Mnb, MNB, parent ion, Diagnoses and Examination, tyrosine-protein kinase Kit, ammonium salt, Postmortem Diagnoses, Step, MS/MS, N-(2, cobaltous formate, common, L-Cysteine, kit, MASS, CG4299, Colony-stimulating factor, Csfgm, AW124434, Bioworks Browser, Dissociation, Treatments, L-Cystein, Labelings, precursor ion, Patient, Biochemical Marker, STEP, copper salt, Liquid, Polypeptide, i2pp2a, 2600005K24Rik, MOPS, CG1849, nat5, human being, Cysteine Hydrochloride, Exovesicles, Bodies, Clinical Markers, Dissociative Reaction, neurologic disorder, Histological Labelings, cesium salt, Vesicles, SCF receptor activity, L Isomer, FBN, Gene, NAT5P, Database, Computer, electron, PHAPII, LC-MS-MS, Cerebrospinal, Surrogate End Points, Buffer, formic acid, Protein Sequence Databases, cytohesin/GRP1, Surrogate Markers, morpholine propanesulphonic acid, potassium salt, scfr, Homo sapiens, polypeptide chain, ECTOL1, 14C-labeled, Clinical Progression, L-Methionine, Histological, A-10, SCFR, Separated, GMCSF, Pedameth, study, Biomarker, Blood Plasma, Fdc, Staining, MS2, iones, BM600, Runt, Biological Marker, gel, ipp2a2, l(2)SH2 0323, SWISS PROT, calcium formate, EBR2, Probabilities, OCTD, Molgramostin, Immunologic Markers, generalised multiple sclerosis, Neural-specific protein-tyrosine phosphatase, DmelCG11387, taf-ibeta, Protein Structure, stem node, Clients, Blood Plasmas, DmelCG12352, Disorder, Cerebral Spinal Fluid, NAT5, Nat5, Structure Database, Ultra Performance Liquid Chromatography, cromium (+3) salt, generalized multiple sclerosis, Immunologic Marker, sodium formate, High-Performance Liquid Chromatography, span, Positron, Applications Software, Open Source, Disease, DYRK1, Computer Software, nickel formate, 3H-labeled, DL-Methionine, protein complex, EBR2A, Negatron, Apoptotic Bodies, DmelCG1849, igaad, End Point, strontium formate, Cerebrospinal Fluids, strontium salt, Client, Labeling, Examination and Diagnoses, Peptide, group, AW112078, LC/MS/MS, Software Tool, Period, natural protein, Sargramostim, Protein, I2PP2A, Dyrk1, Amino Acid Sequence Databases, Fast Electrons, l(2)SH0323, Software, Exovesicle, ACETONITRILE, tandem MS, Zystein, cyanomethane, WMS2, Data Base, CYH1, Plasma, SAN, San, Separation, c-KIT, Serum Marker, PRSS, Reactions, negatron, nodal stem, 2-amino-3-sulfanylpropanoic acid, CC1, Engineering, Tripcellim, Databases, neurologic disease, portion of plasma, L-2-Amino-3-mercaptopropionic acid, patient, l(1)19Ea, Surrogate Marker, sample population, chromic formate, Acute Fulminating, Protein Gene Products, P235, san, Trypure, dSET/TAF-Ibeta, c-kit, 2610030F17Rik, Therapeutic, Ion, Modern Man, SSKS, calcium salt, alpha-amino-gamma-methylmercaptobutyric acid, Treatment, Peptid, High Performance Liquid, Structure Databases, AA407739, nervous system disorder"],"additional_accession":["PXD043337"]},"is_claimable":false,"name":"Proteomic profile of extracellular vesicles from plasma and CSF of multiple sclerosis patients reveals disease activity-associated EAAT2","description":"Multiple Sclerosis (MS) is the most common disabling neurologic disease of young people. The pathological course of MS is heterogeneous in clinical manifestations, response to therapies and outcome, in addition to distinctive clinical courses. For relapsing  remitting multiple sclerosis (RRMS) there is need to identify accurately relapse , defined as new or worsening clinical symptoms associated with an acute inflammatory demyelinating event which is followed by remission, in order to diagnose and classify the clinical course as well as to guide patient management reliable. In this study, the protein composition of Extracellular Vesicles, purified from plasma and cerebrospinal fluid (CSF) samples of RRMS patients with relapse and in remission, were evaluated through a proteomic approach to identify candidate biomarkers for MS relapse. \nProteins extracted from each sample were loaded on a gradient polyacrylamide gel,  run in MOPS buffer and stained with the colloidal blue staining kit.\nEach gel lane was cut into at least 10 contiguous slices, which were subjected to trypsin digestion after reduction and alkylation steps. The resulting peptide mixtures were separated by a nanoflow reversed phase liquid chromatography tandem mass spectrometry using an Ultimate 3000  HPLC connected with a linear ion trap (LTQ XL, ThermoElectron, San Jose, CA, USA) equipped with a nano  electrospray ion source (ESI). Peptides were desalted in a trap column and separated in a 10 cm long reverse phase column slurry  packed in  house with 5 um, 200 A pore size C18 resin.\nPeptides were eluted using a 50 minutes linear gradient from 4 to 80% buffer B (95% acetonitrile and 0.1% formic acid) while buffer A was constituted by 5% acetonitrile and 0.1% formic acid, at 300 nL/min flow rate. Peptide separation was preceded by a 5 min equilibration step at 4% buffer B and followed by 3 min washing step at 90% buffer B and an additional 10 min equilibration period. Analyses were performed in positive mode with high voltage potential at around 1.7 kV. Full MS spectra (m/z 400 to 2000 mass range) were acquired in a data  dependent mode in which each full MS scan was followed by five MS/MS scans; the five most abundant molecular ions were dynamically selected and fragmented by collision  induced dissociation, using a normalized collision energy of 35%.  Target ions already fragmented were dynamically excluded for 45 s.\nTandem mass spectra from plasma sample were matched against the Homo Sapiens protein Swiss Prot database and through the SEQUEST algorithm incorporated in the Bioworks software (version 3.3, Thermo Electron). The following match parameters were considered: fully tryptic cleavage constraints (one miss  cleavage allowed), static cysteine carbamidomethylation, and variable methionine oxidation. Precursor and fragment ions were searched with 1.5 and 1 Da tolerance, respectively. A peptide has been considered legitimately identified when it achieved cross correlation scores of 1.8, 2.5 and 3 for 1, 2 and 3 peptide charge state, respectively, and peptide probability cut  off of P < 0.001. Proteins were identified with at least two peptides.\nFor CSF samples tandem mass spectra  were investigated using Proteome Discoverer 1.4 (Thermo Fisher Scientific).Spectral matches were filtered using Percolator node, based on q values, with 1% false discovery rate (FDR). Only master proteins were taken into account and only specific trypsin cleavages with two miscleavages were admitted. Cysteine carbamydomethylation was set as static modification, while methionine oxidation was set as variable modifications. \n","dates":{"publication":"Tue Jun 27 04:32:00 BST 2023"},"accession":"MSV000092276","cross_references":{}}