MassIVEapplication/xmlftp://massive-ftp.ucsd.edu/v06/MSV000093116/primaryOK200Amber L. Mosleyhttps://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=d94eaa1cb96d476a84d7bc6387e72345almosley@iu.eduMassIVE155UNIMOD:738 - "Duplex Tandem Mass Tag."ProteomicsOrbitrap Exploris 480Homo Sapiens (ncbitaxon:9606)Indiana University School of Medicine<h4>Objectives</h4>The objective of this study was to compare plasma proteomes of patients with confirmed fracture-related infections (FRIs) matched to noninfected controls using liquid chromatography-mass spectrometry.<h4>Methods</h4><h4>Design</h4>This was a prospective case-control study.<h4>Setting</h4>The study was conducted at a single, academic, Level 1 trauma center.<h4>Patient selection criteria</h4>Patients meeting confirmatory FRI criteria were matched to controls without infection based on fracture region, age, and time after surgery from June 2019 to January 2022. Tandem mass tag liquid chromatography-mass spectrometry analysis of patient plasma samples was performed.<h4>Outcome measures and comparisons</h4>Protein abundance ratios in plasma for patients with FRI compared with those for matched controls without infection were calculated.<h4>Results</h4>Twenty-seven patients meeting confirmatory FRI criteria were matched to 27 controls. Abundance ratios for more than 1000 proteins were measured in the 54 plasma samples. Seventy-three proteins were found to be increased or decreased in patients with FRI compared with those in matched controls (unadjusted t test P < 0.05). Thirty-two of these proteins were found in all 54 patient samples and underwent subsequent principal component analysis to reduce the dimensionality of the large proteomics dataset. A 3-component principal component analysis accounted for 45.7% of the variation in the dataset and had 88.9% specificity for the diagnosis of FRI. STRING protein-protein interaction network analysis of these 3 PCs revealed activation of the complement and coagulation cascades through the Reactome pathway database (false discovery rates <0.05).<h4>Conclusions</h4>Proteomic analyses of plasma from patients with FRI demonstrate systemic activation of the complement and coagulation cascades. Further investigation along these lines may help to better understand the systemic response to FRI and improve diagnostic strategies using proteomics.<h4>Level of evidence</h4>Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.Proteomic Analyses of Plasma From Patients With Fracture-Related Infection Reveals Systemic Activation of the Complement and Coagulation Cascades.Becker Kevin K, Sharma Ishani I, Slaven James E JE, Mosley Amber L AL, Doud Emma H EH, Malek Sarah S, Natoli Roman M RMRecovery from surgery, FLOWERING LOCUS A, Antemortem Diagnosis, determination, Blood, fracture, Liquid Chromatography Mass Spectrometry, High Performance Liquid Chromatography Mass Spectrometry, Ultra Performance Liquid Chromatography-Mass Spectrometry, protein, Principal Component Analyses, Diagnosis, Long Term, High Performance Liquid Chromatography-Mass Spectrometry, protein polypeptide chains, HPLC-MS, F6N23.25, Liquid Chromatography-Mass, symptoms, F6N23_25, Analysis, protein aggregate, FLA, Effect, present in fewer numbers in organism, WMS, Benson syndrome, Ultra Performance Liquid Chromatography Mass Spectrometry, Fresh Frozen Plasmas, Fresh Frozen, increased, amyloidosis, Pca-1, Analyses, proteins, bone fracture, twy, FRIGIDA, SURGICAL AND MEDICAL PROCEDURES, decreased, Liquid Chromatography-Mass Spectrometries, GPHYSD2, Long-Term Effects, plasma, Diagnose, SGS, screening, Frozen Plasma, Data Set, Pdnp1, familial, Longterm Effect, arteria cerebri communicans posterior, fracture of bone, familial cutaneous lichen, Procedure, Plasmas, Diagnoses, ACMICD, TPSG1, S-adenosyl-L-methionine:thiol S-methyltransferase activity, 4833416E15Rik, C76301, Postmortem, Screenings, RENBP, Examinations and Diagnoses, Pca, PCA, POSTERIOR, prt, Postmortem Diagnosis, AXPC1, region, activation, PCS, Diagnoses and Examination, Postmortem Diagnoses, clotting, Fracture, Complement, High Pressure Liquid Chromatography Mass Spectrometry, Broken Bone, Spectrometry, Anaphylaxis, signs, MASS, AGE, Principal Component, Patient, PRSS31, Broken, Liquid, Complement System, PC-1, Fractures, TMT, Bone, Ly-41, DmelCG7761, accessory, Fresh, Passive, CD203c, NPP1, Fresh Frozen Plasma, Effects, FBN, Gene, protein-containing complex, Complement Protein, supernumerary, Intervention or Procedure, polypeptide chain, reduced, ECTOL1, subnumerary, Gene Products, Mass, Screening, Antemortem, Npps, Passive Cutaneous, BIG-1, FLVCR, UPLC-MS, study, Ultra-Performance Liquid Chromatography-Mass Spectrometry, Blood Plasma, network topology analysis, Longterm, interventionDescription, biparietal Alzheimer disease, PANG, Interventional, Spectrometries, Long-Term, Diagnoses and Examinations, decreased number, lichen amyloidosis, OCTD, Broken Bones, Clients, Blood Plasmas, site, MFSD7B, Hemolytic, Long-Term Effect, Chromatography-Mass Spectrometries, TAG, thiol methyltransferase activity, Peptidomics., Intervention Strategies, Antemortem Diagnoses, findings, Bone Fractures, RnBP, protein complex, Proteins, GlcNAc 2-epimerase, High Pressure Liquid Chromatography-Mass Spectrometry, Client, Examination and Diagnoses, Cutaneous Anaphylaxis, Frozen Plasmas, M6S1, N-acetyl-D-glucosamine 2-epimerase, native protein, CG7761, natural protein, Mass Screenings, AI428932, Long Term Effects, chemical analysis, Protein, sequence, MFS1, Hemolytic Complement, WMS2, Data Base, Intervention, Plasma, covalent modifier, increased number, choanal atresia, portion of plasma, patient, fracture(s), Bones, primary structure of sequence macromolecule, Longterm Effects, Protein Gene Products, Gene Proteins, present in greater numbers in organism, Complement Proteins, PCARP, SSKS, Chromatography-Mass Spectrometry, renin-binding protein, LC-MS, assay, E-NPP1, ttwRecovery from surgery, Selection for Treatment, FLOWERING LOCUS A, Antemortem Diagnosis, Recruitments, Wound, Blood, Case Referent Studies, fracture, Liquid Chromatography Mass Spectrometry, Physical, Mbp1, Infestations and Infections, High Performance Liquid Chromatography Mass Spectrometry, Subject Selections, L[[3]]CP3., Research Subject Recruitment, Ultra Performance Liquid Chromatography-Mass Spectrometry, protein, Principal Component Analyses, injury, Diagnosis, Long Term, High Performance Liquid Chromatography-Mass Spectrometry, trauma, Techniques, protein polypeptide chains, HPLC-MS, F6N23.25, Liquid Chromatography-Mass, Method, Case Referrent Studies, symptoms, 3, F6N23_25, Analysis, protein aggregate, myd, FLA, Effect, present in fewer numbers in organism, Research-Related, WMS, Matched Case-Control Study, Nested Case-Control Studies, Fresh Frozen Plasmas, Fresh Frozen, Ultra Performance Liquid Chromatography Mass Spectrometry, increased, Selection, Case-Referrent Studies, Analyses, Research Subject Recruitments, Matched, Case Base Studies, Case Control, Mbp-1, proteins, bone fracture, procedures, Subject Recruitment, FRIGIDA, Case-Compeer, decreased, Methodological Studies, Liquid Chromatography-Mass Spectrometries, CG7776, Infections and Infestations, Patient Recruitment, GPHYSD2, Nested Case Control Studies, Long-Term Effects, plasma, Diagnose, SGS, Research Subject Selection, screening, Frozen Plasma, Data Set, gyltl1b-b, Injury and Wounds, Recruitment, e(Pc), Case-Compeer Studies, Longterm Effect, arteria cerebri communicans posterior, Physical Traumas, fracture of bone, Case-Comparison Study, Case-Base Studies, Selection of Research Volunteers, Procedure, Plasmas, Diagnoses, Selections, ACMICD, Case-Referent Studies, wounds, Research Subject, Postmortem, Screenings, MDDGA6, RENBP, mKIAA0609, Examinations and Diagnoses, PCA, prt, Physical Trauma, Subject Selection, Postmortem Diagnosis, KIAA0609, region, activation, Volunteers Selection, fg, Diagnoses and Examination, PCS, Case-Referent Study, Postmortem Diagnoses, clotting, gyltl1b, DmelCG7776, Fracture, Complement, High Pressure Liquid Chromatography Mass Spectrometry, Broken Bone, mdc1d, Spectrometry, expanded, signs, Infection and Infestation, Methodological, MASS, Matched Case-Control, Methodological Study, Treatments, Case-Comparison, AGE, MDC1D, Principal Component, enr, Patient, enlarged, DmelLcp3, E(PC), BG:DS02740.11, anon-48Ac, Broken, Liquid, Research-Related Injuries, Complement System, Fractures, Matched Case-Control Studies, Research-Related Injury, Subjects Selections, Proteomes, Bone, DmelCG7761, accessory, Fresh, big, Research Related Injuries, GH05739, Fresh Frozen Plasma, Procedures, Effects, Peptidomics, FBN, Gene, protein-containing complex, Complement Protein, Case-Comparison Studies, Injuries and Wounds, supernumerary, froggy, Gyltl1a, large, Research Volunteers Selection, Wounds, III, Research Volunteers Selections, polypeptide chain, reduced, GH14582, ECTOL1, subnumerary, Subjects Selection, Studies, Gene Products, Mass, Screening, Nested Case-Control, Antemortem, Research Subject Selections, Technique, BIG-1, DmelCG2043, study, UPLC-MS, Blood Plasma, Ultra-Performance Liquid Chromatography-Mass Spectrometry, network topology analysis, Injury, Case-Referent, lcp3, Research, Criteria, Longterm, Subject Recruitments, MDDGB6, PANG, LCP-3, Spectrometries, Case Control Studies, Case-Control Study, Selection Criteria, LARGE, Long-Term, Diagnoses and Examinations, decreased number, clinical infection, OCTD, Study, BPFD#36, Infestation and Infection, CP3, Broken Bones, Case-Control, Selection for, Clients, Traumas, Blood Plasmas, great, site, Hemolytic, Long-Term Effect, Chromatography-Mass Spectrometries, TAG, Antemortem Diagnoses, findings, LcpIII, Bone Fractures, RnBP, protein complex, Proteins, GlcNAc 2-epimerase, Selection of Subjects, High Pressure Liquid Chromatography-Mass Spectrometry, Client, Examination and Diagnoses, Frozen Plasmas, N-acetyl-D-glucosamine 2-epimerase, native protein, CG7761, Case-Referrent, natural protein, traumatic injury, Wounds and Injury, Mass Screenings, Trauma, Long Term Effects, Protein, Infection, sequence, MFS1, techniques, Hemolytic Complement, LCP3, WMS2, Data Base, Matched Case Control Studies, Plasma, covalent modifier, Nested, DMLCP3, l(2)28-28-12, increased number, Case-Control Studies, wound, portion of plasma, Case-Base, Case-Referrent Study, anon-35Fa, patient, fracture(s), Bones, Selection for Treatments, Nested Case-Control Study, primary structure of sequence macromolecule, Injuries, Longterm Effects, Protein Gene Products, DmelCG5861, Gene Proteins, present in greater numbers in organism, Complement Proteins, Case Comparison Studies, anon-35Fc, Chromatography-Mass Spectrometry, SSKS, Case Control Study, renin-binding protein, LC-MS, Treatment, CG2043, methodologyPlasma, Fresh, Fresh Frozen Plasmas, Fresh Frozen, Blood Plasma, Frozen Plasma, Bone Fractures, Fresh Frozen Plasma, Fracture, Complement, Blood, Broken Bone, fracture, Proteins, Infestations and Infections, portion of plasma, fracture of bone, Infection and Infestation, bone fracture, fracture(s), Bones, Complement Protein, Plasmas, clinical infection, Client, Frozen Plasmas, Infestation and Infection, Complement Proteins, Broken Bones, Patient, Clients, Blood Plasmas, Protein, Broken, Infection, Complement System, Fractures, Hemolytic, Infections and Infestations, Hemolytic Complement, Bone, plasma, activation, clotting.Plasma, Fresh, Fresh Frozen Plasmas, Fresh Frozen, Blood Plasma, Frozen Plasma, Bone Fractures, Fresh Frozen Plasma, Fracture, Complement, Blood, Broken Bone, fracture, Proteins, Infestations and Infections, portion of plasma, fracture of bone, Infection and Infestation, bone fracture, fracture(s), Bones, Complement Protein, Plasmas, clinical infection, Client, Frozen Plasmas, Infestation and Infection, Complement Proteins, Broken Bones, Patient, Clients, Blood Plasmas, Protein, Broken, Infection, Complement System, Fractures, Hemolytic, Infections and Infestations, Hemolytic Complement, Bone, plasma, activation, clotting.PXD046141falseProteomic Analyses of Plasma from Patients with Fracture Related Infection Reveals Systemic Activation of the Complement and Coagulation CascadesPatients/Participants: Twenty-seven patients meeting confirmatory FRI criteria were matched to 27 controls based on fracture region, age, and time after surgery Intervention: Tandem Mass Tag (TMT) LC-MS analysis of patient plasma samples Main Outcome Measurements: Abundances for over 1000 proteins were measured in the 54 plasma samples and the protein abundance ratios for FRI patients compared to matched controls were calculated. Results: Seventy-three proteins were found to be significantly increased or decreased in FRI patients compared to the matched controls (unadjusted t-test p<0.05). Thirty-two of these proteins were found in all 54 patient samples and underwent subsequent principal component analysis (PCA). A three component PCA accounted for 45.7% of the variation in the data set and was 88.9% specific for the diagnosis of FRI. STRING protein-protein interaction network analysis of these three PCs revealed activation of the complement and coagulation cascades via the Reactome pathway database. Conclusions: Proteomic analyses of plasma from FRI patients demonstrates systemic activation of the complement and coagulation cascades in a highly specific manner. Further investigation along these lines may help to better understand the systemic response to FRI and improve diagnostic strategies using proteomics. Sun Oct 15 11:40:00 BST 2023MSV00009311638117580