{"database":"panorama","file_versions":[],"scores":{"citationCount":0,"reanalysisCount":0,"viewCount":0,"searchCount":0},"additional":{"omics_type":["Proteomics"],"submitter":["Astrid Guldbrandsen"],"species":["Homo Sapiens","Rattus Norvegicus"],"full_dataset_link":["https://panoramaweb.org/PRM_Assay_CSF.url"],"submitter_email":["astrid.guldbrandsen@uib.no"],"submitter_affiliation":["Proteomics Unit (PROBE), Department of Biomedicine, University of Bergen, Norway"],"sample_protocol":[""],"repository":["PanoramaPublic"],"data_protocol":[""],"pubmed_abstract":["<h4>Background</h4>Verification of cerebrospinal fluid (CSF) biomarkers for multiple sclerosis and other neurological diseases is a major challenge due to a large number of candidates, limited sample material availability, disease and biological heterogeneity, and the lack of standardized assays. Furthermore, verification studies are often based on a low number of proteins from a single discovery experiment in medium-sized cohorts, where antibodies and surrogate peptides may differ, thus only providing an indication of proteins affected by the disease and not revealing the bigger picture or concluding on the validity of the markers. We here present a standard approach for locating promising biomarker candidates based on existing knowledge, resulting in high-quality assays covering the main biological processes affected by multiple sclerosis for comparable measurements over time.<h4>Methods</h4>Biomarker candidates were located in CSF-PR (proteomics.uib.no/csf-pr), and further filtered based on estimated concentration in CSF and biological function. Peptide surrogates for internal standards were selected according to relevant criteria, parallel reaction monitoring (PRM) assays created, and extensive assay quality testing performed, i.e. intra- and inter-day variation, trypsin digestion status over time, and whether the peptides were able to separate multiple sclerosis patients and controls.<h4>Results</h4>Assays were developed for 25 proteins, represented by 72 peptides selected according to relevant guidelines and available literature and tested for assay peptide suitability. Stability testing revealed 64 peptides with low intra- and inter-day variations, with 44 also being stably digested after 16 h of trypsin digestion, and 37 furthermore showing a significant difference between multiple sclerosis and controls, thereby confirming literature findings. Calibration curves and the linear area of measurement have, so far, been determined for 17 of these peptides.<h4>Conclusions</h4>We present 37 high-quality PRM assays across 21 CSF-proteins found to be affected by multiple sclerosis, along with a recommended workflow for future development of new assays. The assays can directly be used by others, thus enabling better comparison between studies. Finally, the assays can robustly and stably monitor biological processes in multiple sclerosis patients over time, thus potentially aiding in diagnosis and prognosis, and ultimately in treatment decisions."],"pubmed_title":["Development of robust targeted proteomics assays for cerebrospinal fluid biomarkers in multiple sclerosis."],"pubmed_authors":["Guldbrandsen Astrid A, Lereim Ragnhild Reehorst RR, Jacobsen Mari M, Garberg Hilde H, Kroksveen Ann Cathrine AC, Barsnes Harald H, Berven Frode S FS"],"description_synonyms":["FBgn0003149, Rat, Biological Markers, Viral Marker, artificial sequence, Surrogate Endpoints, Laboratory, Blood, Biochemical, Endpoint, Norway Rat, Visible Light, Serum, Model Calibration, Norway Rats, Polypeptides, B2T, Laboratory Markers, rat, Para, \"Multiple sclerosis\" EXACT [SNOMEDCT_2005_07_31:155023009], cerebral spinal fluid, peptido, diseases, Biological, Mammals, hnu, symptoms, liquor cerebrospinalis, diseases and disorders, Norway rat, CG5939, foton, Fresh Frozen Plasmas, Fresh Frozen, human disease, me75, peptides, D17Mit170, T1, Laboratory Rat, reaction, TNFSF14, Immune, Markers, Viral Markers, Homo sapiens disease, gamma, Cerebro Spinal Fluid, screening, Disseminated Sclerosis, Frozen Plasma, Viral, anatomical protrusion, Radiation, Surrogate Endpoint, UNQ391/PRO726, DmelCG5939, Biochemical Markers, Light, Rattus, Tl3, Biologic Marker, Tl2, Plasmas, Cerebro Spinal Fluids, Literatures, Mus norvegicus, LIGHT, Rattus norwegicus, prm, Marker, Diseases, \"Generalized multiple sclerosis (disorder)\" EXACT [SNOMEDCT_2005_07_31:192928003], l(3)S010605, Sensor, Visible Radiations, LAMB2T, Visible Radiation, HVEML, End Points, 0106/05, PM/mPM, signs, \"insular sclerosis\" EXACT [CSP2005:2042-2324], Immunologic, Colony-stimulating factor, Csfgm, Laboratory Marker, Cerebro, beta Trypsin, rats, Multiple, disease, SYNTHETIC CONSTRUCT sequences, light quantum, Biochemical Marker, spine, Sensor Calibration, Sensor Calibrations, artificial, 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disorder, peptidos, TR2, generalized multiple sclerosis, Model, Immunologic Marker, Biologic, Rattus norvegicus8, findings, cou, EBR2A, Proteins, Serum Markers, disorders, Fluids, End Point, Cerebrospinal Fluids, artificial gene, spinal fluid, medical condition, MS (Multiple Sclerosis), synthetic DNA, CD258, Peptide, Spinal Fluid, Immune Marker, Frozen Plasmas, Spinal Fluids, MS, Lr, Fluid, Sargramostim, Surrogate End Point, Model Calibrations, Laboratory Rats, Protein, synthetic, condition, plasma., Biologic Markers, Radiations, Plasma, Serum Marker, PRSS, Surrogate, HVEM-L, Endpoints, Photoradiation, Tripcellim, portion of plasma, CSF, Disseminated, synthetic constructs, Surrogate Marker, Acute Fulminating, LTg, Protein Gene Products, Gene Proteins, Trypure, Photoradiations, l(3)10631, Calibration, LAMNB2, Calibrations, Bra, Peptid, Norway, pm, PM, Immune Markers, Gunn rats"],"pubmed_title_synonyms":["\"multiple sclerosis\" EXACT [NCI2004_11_17:C3243], Cerebro Spinal Fluid, Disseminated Sclerosis, Biological Markers, Viral Marker, Viral, Surrogate Endpoints, single-organism developmental process, Surrogate Endpoint, Peptidomics, Clinical Markers, Laboratory, Clinical Marker, Sclerosis, postnatal development, Serum Markers, Multiple Sclerosis, Fluids, Biochemical, End Point, Cerebrospinal Fluids, Endpoint, growth and development, Biochemical Markers, spinal fluid, MS (Multiple Sclerosis), Serum, Biologic Marker, Spinal Fluid, Immune Marker, Cerebrospinal, Surrogate End Points, Cerebro Spinal Fluids, development, Spinal Fluids, Surrogate Markers, Laboratory Markers, MS, \"Multiple sclerosis\" EXACT [SNOMEDCT_2005_07_31:155023009], Fluid, cerebral spinal fluid, Marker, Biological, Surrogate End Point, Cerebro Spinal, liquor cerebrospinalis, \"Generalized multiple sclerosis (disorder)\" EXACT [SNOMEDCT_2005_07_31:192928003], Biologic Markers, \"Multiple sclerosis (disorder)\" EXACT [SNOMEDCT_2005_07_31:24700007], Biomarker, \"Multiple sclerosis NOS (disorder)\" EXACT [SNOMEDCT_2005_07_31:192930001], Serum Marker, Clinical, End Points, Surrogate, Biological Marker, Endpoints, postnatal growth, \"insular sclerosis\" EXACT [CSP2005:2042-2324], CSF, Immunologic, Laboratory Marker, Cerebro, Disseminated, Surrogate Marker, Acute Fulminating, Multiple, Immunologic Markers, Immune, generalised multiple sclerosis, Markers, Biochemical Marker, Viral Markers, generalized multiple sclerosis, growth, Immunologic Marker, \"Multiple sclerosis\" EXACT [ICD9CM_2006:340]., Biologic, Immune Markers"],"name_synonyms":["\"multiple sclerosis\" EXACT [NCI2004_11_17:C3243], measuring, Cerebro Spinal Fluid, Disseminated Sclerosis, Biological Markers, Viral Marker, Viral, Surrogate Endpoints, single-organism developmental process, Surrogate Endpoint, determination, Clinical Markers, Laboratory, Clinical Marker, Sclerosis, postnatal development, Multiple Sclerosis, Serum Markers, Biochemical, Fluids, End Point, Endpoint, Cerebrospinal Fluids, growth and development, Biochemical Markers, spinal fluid, MS (Multiple Sclerosis), Serum, Biologic Marker, Spinal Fluid, Immune Marker, Surrogate End Points, Cerebrospinal, Cerebro Spinal Fluids, development, Surrogate Markers, Spinal Fluids, Laboratory Markers, MS, \"Multiple sclerosis\" EXACT [SNOMEDCT_2005_07_31:155023009], Fluid, cerebral spinal fluid, Marker, Biological, Surrogate End Point, chemical analysis, Cerebro., Cerebro Spinal, \"Generalized multiple sclerosis (disorder)\" EXACT [SNOMEDCT_2005_07_31:192928003], liquor cerebrospinalis, \"Multiple sclerosis\" EXACT [ICD9CM_2006:340], Biologic Markers, \"Multiple sclerosis (disorder)\" EXACT [SNOMEDCT_2005_07_31:24700007], \"Multiple sclerosis NOS (disorder)\" EXACT [SNOMEDCT_2005_07_31:192930001], Biomarker, Serum Marker, Clinical, End Points, Surrogate, Biological Marker, Endpoints, postnatal growth, \"insular sclerosis\" EXACT [CSP2005:2042-2324], Immunologic, CSF, Laboratory Marker, Cerebro, Disseminated, Surrogate Marker, Acute 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reaction, Immune, Markers, Methodological Studies, Smurf, scientific observation, Viral Markers, sample, Therapies, Homo sapiens disease, Reference Standard, Long-Term Effects, CG4943, Diagnose, D-smurf, Predictions and Projections, Therapy, Cerebro Spinal Fluid, screening, Disseminated Sclerosis, Standard Preparation, Standard Preparations, Viral, anatomical protrusion, Standardization, Surrogate Endpoint, PLATEST, CG6383, gyltl1b-b, DmelCG5939, Longterm Effect, Biochemical Markers, Lack, Procedure, Tl3, antibodies, Biologic Marker, Tl2, results, Diagnoses, Cerebro Spinal Fluids, Literatures, Workflows, Postmortem, Screenings, prm, Marker, MDDGA6, mKIAA0609, Examinations and Diagnoses, Diseases, \"Generalized multiple sclerosis (disorder)\" EXACT [SNOMEDCT_2005_07_31:192928003], l(3)S010605, Postmortem Diagnosis, KIAA0609, Sensor, fg, Diagnoses and Examination, LAMB2T, Epistemology, Postmortem Diagnoses, gyltl1b, Factors, End Points, DmelCG4943, Standard, 0106/05, Prognostic, PM/mPM, mdc1d, expanded, signs, \"insular sclerosis\" EXACT [CSP2005:2042-2324], Immunologic, Methodological, Colony-stimulating factor, Csfgm, Laboratory Marker, Cerebro, Methodological Study, beta Trypsin, Treatments, Multiple, disease, MDC1D, enr, enlarged, Patient, Biochemical Marker, spine, Sensor Calibration, Sensor Calibrations, Polypeptide, l(3)S050920, Platelets, Work Flows, Prognostic Factor, Crbs, \"multiple sclerosis\" EXACT [NCI2004_11_17:C3243], big, other disease, criteria, Procedures, Clinical Markers, Effects, Peptidomics, Clinical Marker, Sclerosis, dSmurf1, Multiple Sclerosis, number, Gene, GM-CSF, far, Prognostic Factors, guidelines, froggy, Gyltl1a, Cerebrospinal, Surrogate End Points, protrusion, Surrogate Markers, large, Crumbs, mPM, Gene Products, Studies, Mass, Cerebro Spinal, disease or disorder, Screening, Projections and Predictions, Low, Antemortem, \"Multiple sclerosis\" EXACT [ICD9CM_2006:340], Technique, GMCSF, \"Multiple sclerosis (disorder)\" EXACT 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Sargramostim, Surrogate End Point, Mass Screenings, Model Calibrations, Smurf ubiquitin ligase, Protein, Long Term Effects, chemical analysis, condition, CRB, Crb, background, techniques, l(3)S058104, Biologic Markers, Serum Marker, PRSS, Surrogate, Endpoints, postnatal growth, Tripcellim, CSF, Disseminated, Surrogate Marker, sample population, introduction, Acute Fulminating, Longterm Effects, Protein Gene Products, Gene Proteins, Trypure, Preparations, l(3)10631, Therapeutic, concentration, Calibration, LAMNB2, cardinality, Standards, Calibrations, Bra, Peptid, Treatment, assay, Future, growth, pm, PM, methodology, Immune Markers"],"citation_count":["0"],"additional_accession":[]},"is_claimable":false,"name":"Parallel reaction monitoring assay development for multiple sclerosis biomarkers in cerebrospinal fluid.","description":"We have developed and tested parallel reaction monitoring (PRM) assays for 25 proteins highly relevant as cerebrospinal fluid (CSF) biomarkers for multiple sclerosis, representing various biological processes affected in the disease. The proteins were represented by 72 peptides selected according to relevant guidelines and available literature. Stability testing revealed 64 peptides with low intra- and inter-day variations, with 44 also being stably digested after 16 hours of trypsin digestion, and 37 furthermore showing a significant difference between multiple sclerosis and controls, thereby confirming literature findings. Calibration curves were developed using spike-in of synthetic light and heavy peptides in rat plasma.","dates":{"publication":"Thu May 20 00:00:00 BST 2021"},"accession":"PXD017281","cross_references":{"TAXONOMY":["9606","10116"],"pubmed":["32963504"]}}