Prideapplication/xmlftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/09/PXD019187/checksum.txtftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/09/PXD019187/metadata_MFM_WB_proteomics_20180105.txtftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/09/PXD019187/rep1_hf2018022305.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/09/PXD019187/rep2_hf2018022328.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/09/PXD019187/rep1_hf2018022310.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/09/PXD019187/rep2_hf2018022331.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/09/PXD019187/rep1_hf2018022306.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/09/PXD019187/rep3_hf2018022349.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/09/PXD019187/rep1_hf2018022304.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/09/PXD019187/rep3_hf2018022354.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/09/PXD019187/rep2_hf2018022327.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/09/PXD019187/rep3_hf2018022353.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/09/PXD019187/rep3_hf2018022348.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/09/PXD019187/rep2_hf2018022321.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/09/PXD019187/rep2_hf2018022330.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/09/PXD019187/rep2_hf2018022329.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/09/PXD019187/rep1_hf2018022312.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/09/PXD019187/rep3_hf2018022347.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/09/PXD019187/rep1_hf2018022311.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/09/PXD019187/rep2_hf2018022320.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/09/PXD019187/rep3_hf2018022346.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/09/PXD019187/rep2_hf2018022323.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/09/PXD019187/rep1_hf2018022309.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/09/PXD019187/rep1_hf2018022314.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/09/PXD019187/rep2_hf2018022324.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/09/PXD019187/rep3_hf2018022350.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/09/PXD019187/rep2_hf2018022322.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/09/PXD019187/rep1_hf2018022313.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/09/PXD019187/rep3_hf2018022345.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/09/PXD019187/rep1_hf2018022307.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/09/PXD019187/rep3_hf2018022352.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/09/PXD019187/rep2_hf2018022326.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/09/PXD019187/rep3_hf2018022344.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/09/PXD019187/rep3_hf2018022343.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/09/PXD019187/rep1_hf2018022315.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/09/PXD019187/rep1_hf2018022308.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/09/PXD019187/rep2_hf2018022325.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/09/PXD019187/rep3_hf2018022351.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/09/PXD019187/WB_proteomics_merged_20180906.mzid.gzftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/09/PXD019187/WB_proteomics_merged_20180906.mzid_Mudpit_2018_6_22_52_PM_File_Size__978857276__Byte__(F010583).pride.mgf.gzftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/09/PXD019187/WB_proteomics_merged_20180906.mzid_Mudpit_2018_5_13_40_PM_File_Size__703527597__Byte__F010569.MGFftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/09/PXD019187/WB_proteomics_merged_20180906.mzid_Mudpit_2018_6_22_52_PM_File_Size__978857276__Byte__F010583.MGFftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/09/PXD019187/WB_proteomics_merged_20180906.mzid_Mudpit_2018_5_21_33_PM_File_Size__638456384__Byte__F010557.MGFftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/09/PXD019187/WB_proteomics_merged_20180906.mzid_Mudpit_2018_5_21_33_PM_File_Size__638456384__Byte__(F010557).pride.mgf.gzftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/09/PXD019187/WB_proteomics_merged_20180906.mzid_Mudpit_2018_5_13_40_PM_File_Size__703527597__Byte__(F010569).pride.mgf.gzftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/09/PXD019187/UP000002281-GCA_002863925.1-cRAP.fastaftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/09/PXD019187/WB_proteomics_merged_20180906.pride.mztab.gzftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/09/PXD019187/ScaffoldQuantMLReportforWB_proteomics_merged_20180906.sqmlftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/09/PXD019187/WB_proteomics_merged_20180906.sf3primaryOK200Stephanie ValbergMascot 2.6.0X! Tandem CYCLONE (2010.12.01.1)Scaffold Scaffold_4.8.7Skeletal Muscle FiberSkeletal MuscleMuscle samples from nine horses were analyzed using a 10-plex tandem mas tag protein quantitation assay. Five MFM WB (2 castrated males, 1 male and 2 females) with the mean age of 14.4 ± 3yrs, four non-MFM WB (2 castrated males and 2 females) with the mean age of 13.8 ± 4.6yrs, and one technical replicate were included in the assay. Proteins was extracted from snap frozen gluteal muscle biopsies with radioimmunoprecipitation lysis buffer and quantified. Five hundred µg from each sample were digested in trypsin, labeled with TMT10 reagents, fractionated, and eluted from RSLC columns. The eluted peptides were sprayed into a ThermoScientific Q-Exactive HF-X mass spectrometer. Survey scans were taken in the Orbi trap (120,000 resolution, determined at m/z 200) and the top twenty ions in each survey scan subjected to automatic higher energy collision induced dissociation with fragment spectra acquired at 45,000 resolution.PrideStephanie ValbergQ Exactive HFCOMPLETEMary Anne McPhail Dressage Chair in Equine Sports Medicine Department Large Animal Clinical Sciences College of Veterinary Medicine Michigan State University34112090 Williams ZJ, Velez-Irizarry D, Gardner K, Valberg SJ. Integrated proteomic and transcriptomic profiling identifies aberrant gene and protein expression in the sarcomere, mitochondrial complex I, and the extracellular matrix in Warmblood horses with myofibrillar myopathy. BMC Genomics. 2021 22(1):438 10.1186/s12864-021-07758-0Michigan State Universityvalbergs@msu.eduMass SpectrometryShotgun proteomicsMyofibrillar MyopathyLc-msmsGluteal muscleHorsehttp://www.ebi.ac.uk/pride/archive/projects/PXD019187TMTCarbamidomethylDehydratedAmmonia-lossiodoacetamide derivatized residuemethionine oxidation with neutral loss of 64 DaAcetylOxidationTMT6plex-126 reporter+balance reagent acylated residuemono N-acetylated residueTMT6plexThe resulting MS/MS spectra were converted to peak lists using Proteome Discoverer, v2.2 and searched against the UniprotKB Equus caballus reference proteome (UP000002281) appended with common laboratory contaminants using the Sequest HT search algorithm. The search output was then analyzed using Scaffold, v4.8.4 to probabilistically validate protein identifications (FDR < 0.01) . Spectra data were log-transformed, pruned of those matched to multiple proteins (retaining proteins with at least two identified peptides), and weighted by an adaptive intensity weighting algorithm. Of 108665 spectra in the experiment at the given thresholds, 79921 (74%) were included in quantitation. Differentially expressed proteins were determined by applying Permutation Test and corrected by Benjamini-Hochberg (FDR ≤ 0.05, P ≤ 0.003).ProteomicsEquus Caballus (horse)valbergs@msu.eduUnited States10.6019/PXD019187<h4>Background</h4>Myofibrillar myopathy in humans causes protein aggregation, degeneration, and weakness of skeletal muscle. In horses, myofibrillar myopathy is a late-onset disease of unknown origin characterized by poor performance, atrophy, myofibrillar disarray, and desmin aggregation in skeletal muscle. This study evaluated molecular and ultrastructural signatures of myofibrillar myopathy in Warmblood horses through gluteal muscle tandem-mass-tag quantitative proteomics (5 affected, 4 control), mRNA-sequencing (8 affected, 8 control), amalgamated gene ontology analyses, and immunofluorescent and electron microscopy.<h4>Results</h4>We identified 93/1533 proteins and 47/27,690 genes that were significantly differentially expressed. The top significantly differentially expressed protein CSRP3 and three other differentially expressed proteins, including, PDLIM3, SYNPO2, and SYNPOL2, are integrally involved in Z-disc signaling, gene transcription and subsequently sarcomere integrity. Through immunofluorescent staining, both desmin aggregates and CSRP3 were localized to type 2A fibers. The highest differentially expressed gene CHAC1, whose protein product degrades glutathione, is associated with oxidative stress and apoptosis. Amalgamated transcriptomic and proteomic gene ontology analyses identified 3 enriched cellular locations; the sarcomere (Z-disc & I-band), mitochondrial complex I and the extracellular matrix which corresponded to ultrastructural Z-disc disruption and mitochondrial cristae alterations found with electron microscopy.<h4>Conclusions</h4>A combined proteomic and transcriptomic analysis highlighted three enriched cellular locations that correspond with MFM ultrastructural pathology in Warmblood horses. Aberrant Z-disc mechano-signaling, impaired Z-disc stability, decreased mitochondrial complex I expression, and a pro-oxidative cellular environment are hypothesized to contribute to the development of myofibrillar myopathy in Warmblood horses. These molecular signatures may provide further insight into diagnostic biomarkers, treatments, and the underlying pathophysiology of MFM.Integrated proteomic and transcriptomic profiling identifies aberrant gene and protein expression in the sarcomere, mitochondrial complex I, and the extracellular matrix in Warmblood horses with myofibrillar myopathy.Williams Zoë J ZJ, Velez-Irizarry Deborah D, Gardner Keri K, Valberg Stephanie J SJdalpha-SNAP, dalphaSNAP, ion, not genetically inherited., Domestic Horses, MTOC attachment site, TRAP, p50, Ly62, SEC9, PFD, TAPK, Gene, CG11081, protein, bA416N4.2, protein-containing complex, lysis, thomson, gonadotropin-independent female-limited sexual precocity, TR-AP, RP11-508D10.1, mccune-albright syndrome, Buffer, mass-to-charge ratio, Albright's disease, peptide, DmelCG11081, Polypeptides, Tnfsf5, protein polypeptide chains, peptido, polypeptide chain, DPlexA, l(3)77ABa, GP39, technical_replicate, Gene Products, CG6625, l(3)77ABc, D-Plex A, RIC-4, CD40-L, protein aggregate, (2Z)-but-2-enedioate, dJ1068F16.2, alpha-SNAP, Equus przewalskii, MAS, male, gp39, CD154, T-BAM, type 5 acid phosphatase, tartrate-resistant acid ATPase, Biopsies, peptides, GKLP, CATC4, iones, plex A, plex B, beta-Trypsin, proteins, Domestic, ions, study assay, SCAN, CG17245, SNAP-25, DmelCG17245, PCTAIRE2-binding protein, TRAP3, T-cell antigen Gp39, Tudor repeat associator with PCTAIRE-2, MGC:45012, TEIF, Trap, scientific observation, gluteus, musculus, sample, HIGM1, peptidos, autolysin activity, necrosis, TNFSF5, T5ap, Horses, MGC - 45012, TAG, C78062, CD40L, measuring, P105, NTKL, DmelCG6625, dSNAP, female human body, protein complex, Males, PCTAIRE2BP, Tnfrsf5, Proteins, polyostotic fibrous dysplasia, Cd40l, Th, Bp50, Horse, dsnap, ACP5, Domestic Horse, somatic, plex, tag, buffer, SPENCDI, female, Peptide, hCD40L, polypeptide, any method, macrophage activation syndrome, native protein, natural protein, Ionen, Protein, IMD3, bacteriocin activity, TNF-related activation protein, PlexA1, Ly-62, BcDNA:GM05237, reactive hemophagocytic lymphohistiocytosis, Equus caballus, covalent modifier, technical replicate, holin, PlexB, PlexA, maleate, NKTL, Tripcellim, AW743063, alphaSnap, muscle, mosaic, POFD, AI326936, Plex1, beta Trypsin, sample population, muscle element, McCune Albright syndrome, male human body, Protein Gene Products, Gene Proteins, Trypure, lysin activity, Ion, SNAP, TrATPase, RIC4, IGM, microtubule organising centre attachment site, bacteriolytic toxin activity, Peptid, CD40LG, Polypeptide, TRACP, PLEXB, Females, horses, snapatypia, myofibrillar myopathy, aberrant, Domestic Horses, filaminopathy (type), protein complex, Protein surplus myopathy (former name), Matrix, myofibrillar myopathy (disease), defective, protein, Horse, protein-containing complex, Matrices, Domestic Horse, mitochondrial, protein polypeptide chains, native protein, desmin related myopathy (former name), natural protein, polypeptide chain, ATP synthase D chain, NADH dehydrogenase complex (plastoquinone), myofibrillar myopathies, Protein, atypical, Extracellular Matrices, protein aggregate, plastid NADH dehydrogenase complex (plastoquinone), Sarcomere, Equus przewalskii, Equus caballus, Mitochondrial, matrisome, Myofibrillar Myopathies, NADH:plastoquinone reductase complex, Zaspopathy (type), Desminopathy (type)., INSDC_feature:gene, proteins, Domestic, myotilinopathy (type), NADH dehydrogenase complex (quinone), Complex I, desmin storage myopathy (former name), Extracellular, Alpha Beta crystallinopathy (type), NADH dehydrogenase complex (ubiquinone), Horses, proteinaceous extracellular matrix, horsesGene., data, peptides, Laboratory, protein complex, Proteins, total expressed protein, common, Gene, proteins, protein, protein-containing complex, Peptide, Equus przewalskii forma caballus, Protein Gene Products, Gene Proteins, polypeptide, peptide, Polypeptides, protein polypeptide chains, domestic horse, Experiment, native protein, peptido, Equus przewalskii f. caballus, natural protein, polypeptide chain, Equus ferus caballus, Algorithm, Protein, horse, Gene Products, Peptid, peptidos, laboratory, Polypeptide, protein aggregate, Proteomes, equineAA407358, other disease, Skeletin, dalpha-SNAP, dalphaSNAP, Activity, Domestic Horses, determination, filaminopathy (type), Laboratory, Aspect, SEC9, Training, Isometric, Physical, Protein surplus myopathy (former name), histology, slow time, Exercise Training, protein, bA416N4.2, protein-containing complex, Equus przewalskii forma caballus, protein polypeptide chains, diseases, polypeptide chain, Equus ferus caballus, Physical Exercises, l(3)77ABa, horse, disease or disorder, CG6625, diseases and disorders, l(3)77ABc, NRSF, RIC-4, cytopathology, protein aggregate, Acute Exercises, dJ1068F16.2, alpha-SNAP, Equus przewalskii, equine, study, human disease, Aerobic Exercises, Biopsies, reference sample, Rests, preceding., Physical Activity, Age of onset, proteins, Domestic, Histories, Desminopathy (type), SNAP-25, non-neoplastic, domestic horse, desmin, Equus przewalskii f. caballus, grupos, gluteus, musculus, sample, disorder, Chronic, Homo sapiens disease, Alpha Beta crystallinopathy (type), Horses, Exercises, Decreased ability to exercise, Controlled, Inability to exercise, DmelCG6625, Controlling, dSNAP, myofibrillar myopathy, grupo, vimentin, Poor exercise tolerance, protein complex, type III intermediate filament associated protein, disorders, 2610008J04Rik, Exercise, Aerobic, late, TelN, myofibrillar myopathy (disease), Horse, medical condition, Historical Aspects, dsnap, Domestic Horse, increased time, historical aspects, Historical Aspect, chronic, group, desmin related myopathy (former name), native protein, natural protein, XBR, myofibrillar myopathies, increased period, Low exercise endurance, peripherin, Protein, chemical analysis, Diseases, high time, condition, University, Acute Exercise, laboratory, prolonged period, Isometric Exercises, Physical Exercise, glial fibrillary acidic protein, Data Base, Equus caballus, Aerobic Exercise, histopathology, Myofibrillar Myopathies, Rest, Zaspopathy (type), pooled, alphaSnap, muscle, myotilinopathy (type), Age symptoms begin, Trainings, sample population, muscle element, Exercise Trainings, Isometric Exercise, Activities, disease, Acute, Physical Activities, desmin storage myopathy (former name), SNAP, historical notes, RIC4, ResT, assay, Aspects, biopsy, groupe, Historical, Gruppe, horses, snapMaterials, Surrogate Endpoints, filaminopathy (type), Laboratory, A4, CG17228, 1135/09, 1135/07, protein polypeptide chains, Oxidative DNA, Oxidative, Programmed, Biological, 0451/09, Nitro-Oxidative Stresses, Extracellular Matrices, DNA Damage, WMS, 0244/09, Glycine, Reduced, Oxidative Cleavage, DROPROSA, Age of onset, proteins, Glutathione, Reduced glutathione, 671/2, Intrinsic Pathway Apoptosis, Oxidative Stresses, decreased, NADH dehydrogenase complex (quinone), CMH12, Homo sapiens disease, Alpha Beta crystallinopathy (type), transcription from bacterial-type RNA polymerase promoter, Histological Labeling, SGS, single organism signaling, Actn2lp, dysfunction., 1810008K03Rik, Viral, vimentin, DNA-dependent transcription, gamma-L-Glu-L-Cys-Gly, partial functionality, ACMICD, signaling (initiator) caspase activity, induction of apoptosis, ATP synthase D chain, Marker, 1316/02, BcDNA:HL08040, Ontology Projects, DNA Oxidative Damages, Caspase-Dependent, Sarcomere, glial fibrillary acidic protein, Ontology, protein_coding_transcript, Projects, End Points, 1167/13, INSDC_feature:gene, Immunologic, Laboratory Marker, GSH, Nitro-Oxidative, Intrinsic Pathway Apoptoses, Material, Extrinsic Pathway, l(1)16Fg, DNA, 0989/01, humans, Oxidative Damage, pds, atypia, transcription, CLP, localised, Peptidomics, Antioxidative, Clinical Marker, number, impaired, gamma-L-Glutamyl-L-Cysteinylglycine, protein-containing complex, apoptotic programmed cell death, mitochondrial, 0763/13, Gene Ontology Project, activation of apoptosis, Gene Ontology, Human, DmelCG17228, AI463105, Gene Products, disease or disorder, atypical, Prosp, MAM, Man, Oxidative Damages, Equus przewalskii, F15E12_6, Injury, Clinical, dysfunction, messenger RNA, Desminopathy (type), l(3)rH013, template RNA, Prodos, desmin, Antioxidative Stresses, Classic Apoptosis, execution phase of apoptotic process, Extracellular, gamma L Glu L Cys Gly, Horses, L-gamma-glutamyl-L-cysteinylglycine, Biologic, striated muscle, Apoptosis, 0671/02, l(3)j12C8, Alp, cellular transcription, ALP, cell suicide, degeneration, Proteins, apoptotic cell death, Serum Markers, disorders, Stainings, defective, Anti-oxidative Stresses, Immune Marker, l(3)rL433, desmin related myopathy (former name), native protein, l(3)rI160, 0441/16, Surrogate End Point, Oxidative Nitrative Stresses, chemical analysis, stab cell, INSDC_feature:mRNA, condition, MFS1, background, Reduced Glutathione, ATCMPG1, MET, ATCMPG2, Biologic Markers, Ontology Project, covalent modifier, band form, Anti-oxidative Stress, DMDA1, apoptosis, mRNA, DNA Oxidative Damage, Surrogate, Endpoints, Zaspopathy (type), DNA-templated, rod neutrophil, signalling, Classic Apoptoses, l(3)rK204, Gene Proteins, having decreased function, signalling process, apoptotic program, Stress, commitment to apoptosis, Glutathione-SH, quantitative, biopsy, Immune Markers, DNA Oxidative, l(3)rK137, Biological Markers, Viral Marker, Gene Ontology Projects, single-organism developmental process, determination, Biochemical, Nitrative Stress, Endpoint, protein, Serum, type I programmed cell death, band, Damage, dysfunctional, Laboratory Markers, diseases, Extrinsic Pathway Apoptoses, Nitro-Oxidative Stress, gamma-L-Glutamyl-L-cysteinyl-glycine, Project, Impacts, diseases and disorders, cytopathology, Environmental Impacts, protein aggregate, Oxidative Injury, present in fewer numbers in organism, Oxidative Injuries, human disease, Man (Taxonomy), reference sample, MUB3_18, NADH:plastoquinone reductase complex, 5-L-Glutamyl-L-cysteinylglycine, Domestic, Oxidative DNA Damages, MUB3.18, l(3)j6E2, Anti-oxidative, Environmental Impact, DNA-dependent, 0320/10, Oxidative Stress Injuries, band cell, DMPROSPER, Immune, Markers, Classic, signaling process, Viral Markers, Classical Apoptosis, Pathologies, Therapies, associated, GPHYSD2, Therapy, cellular suicide, myofibrillar myopathy, Caspase-Dependent Apoptosis, Surrogate Endpoint, aberrant, l(3)rO534, type III intermediate filament associated protein, PRO, Pro, CRP3, Modern, MLP, cristae, mitochondrial cristae, late, Labeling and Staining, Biochemical Markers, Biologic Marker, CYS, results, Electron Microscopy, PROS-1, PROS-2, myofibrillar myopathies, peripherin, Oxidative and Nitrosative Stress, Intrinsic Pathway, pro, Extrinsic Pathway Apoptosis, Diseases, Genetic Materials, and GLY protein 2, plastid NADH dehydrogenase complex (plastoquinone), Genetic Material, Gene Ontologies, Mitochondrial, and GLY protein 1, Ontologies, histopathology, Voila, 0664/07, MASS, Cell Death, myotilinopathy (type), lacks function of type, TAF[[II]], Treatments, low functionality, disease, DMDA, Labelings, induction of apoptosis by p53, Biochemical Marker, bacterial transcription, Cistron, Oxidative Stress Injury, NADH dehydrogenase complex (ubiquinone), Classical, Apoptoses, MMLP, CMD1M, other disease, Skeletin, Oxidative Stress, biological signaling, Domestic Horses, Clinical Markers, Histological Labelings, caspase-dependent programmed cell death, Protein surplus myopathy (former name), FBN, Antioxidative Stress, Matrix, Gene, Caspase Dependent Apoptosis, Matrices, skeletal muscle, presence, TYPE, Stresses, l(3)10419, Surrogate End Points, DAGA4, N-(N-L-gamma-glutamyl-L-cysteinyl)-, dmTAF8, Surrogate Markers, LMO4, Oxidative Nitrative, Homo sapiens, polypeptide chain, reduced, Stress Injury, ECTOL1, subnumerary, HL-VIII, Oxidative Cleavages, Histological, anon-WO0140519.15, F15E12.6, Type I, SCG3, study, Biomarker, PROS, matrisome, 0585/13, Genetic, Staining, Biological Marker, CG7128, N-(N-gamma-L-Glutamyl-L-cysteinyl)glycine, decreased number, apoptosis activator activity, non-neoplastic, OCTD, gamma L Glutamyl L Cysteinylglycine, prod, Immunologic Markers, Anti oxidative Stress, Oxidative DNA Damage, Complex I, gluteus, disorder, TAF, 0563/18, programmed cell death by apoptosis, Immunologic Marker, TAG, Controlled, Controlling, protein complex, End Point, myofibrillar myopathy (disease), Horse, medical condition, Domestic Horse, tag, Cistrons, Labeling, LGMD2C, l(3)rJ806, Pros, Impact, Environmental, development, somatic muscle, count in organism, Oxidative Nitrative Stress, natural protein, NADH dehydrogenase complex (plastoquinone), Programmed Cell Death, Protein, TFIID, focal, Atrophies, WMS2, Equus caballus, apoptosis signaling, Serum Marker, Myofibrillar Myopathies, pathophysiology, Age symptoms begin, Cleavage, Surrogate Marker, introduction, Protein Gene Products, DmelCG7128, Therapeutic, desmin storage myopathy (former name), Modern Man, SSKS, SCARMD2, Environments, Treatment, assay, TAF8, Nitro Oxidative Stress, proteinaceous extracellular matrix, skeletal muscle system, horses, presence or absence in organismliquid chromatography tandem mass spectroscopy, LC-MS2, LC/MS/MS, domestic horse, LCMSMS, Equus przewalskii f. caballus, Equus ferus caballus, gluteus, liquid chromatography-tandem mass spectroscopy, LC-MSMS, horse, LC-MS/MS, liquid chromatography tandem mass spectrometry, LC-MS-MS., Equus przewalskii forma caballus, equinefalseEquine gluteal muscle LC-MSMS: WarmbloodMyofibrillar myopathy (MFM) in horses is a late onset disease that affects performance and athleticism. It is characterized by myofibrillar disarray and protein aggregation with no known cause. The objective of this study was to elucidate the molecular drivers of MFM in Warmblood (WB) horses by proteomic profiling (5 MFM WB, 4 non-MFM WB) of gluteal muscle. MFM horses used in this study had a chronic history of poor performance and exercise intolerance as well as accumulation of desmin aggregates in > 4 myofibers per muscle sample. The Equine Neuromuscular Diagnostic Laboratory database at Michigan State University was queried to identify WB horses with snap frozen gluteus medius biopsies available for analysis. Non-MFM control horses were defined as horses with no history of exercise intolerance and no evidence of desmin accumulation or other histopathology in muscle biopsies. Muscle biopsy samples were obtained at rest from horses that had not undertaken strenuous exercise in the preceding 48 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