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PXD020493

PXD020493 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleCombined Tissue-Fluid Proteomics to Unravel Phenotypic Variability in Amyotrophic Lateral Sclerosis
DescriptionThe lack of biomarkers for early diagnosis, clinical stratification and to monitor treatment response has hampered the development of new therapies for amyotrophic lateral sclerosis (ALS), a clinically heterogeneous neurodegenerative disorder with a variable site of disease initiation and rate of progression. To identify new biomarkers and therapeutic targets, two separate proteomic workflows were applied to study the immunological response and the plasma/brain proteome in phenotypic variants of ALS. Conventional multiplex (TMT) proteomic analysis of peripheral blood mononuclear cells (PBMCs) was performed alongside a recently introduced method to profile neuronal-derived proteins in plasma using brain tissue-enhanced isobaric tagging (TMTcalibrator). The combined proteomic analysis allowed the detection of regulated proteins linked to ALS pathogenesis (RNA-binding protein FUS, superoxide dismutase Cu-Zn and neurofilaments light polypeptide) alongside newly identified candidate biomarkers (myosin-9, fructose-bisphosphate aldolase and plectin). In line with the proteomic results, orthogonal immunodetection showed changes in neurofilaments and ApoE in bulbar versus limb onset fast progressing ALS. Functional analysis of significantly regulated features showed enrichment of pathways involved in regulation of the immune response, Rho family GTPases, semaphorin and integrin signalling. Our cross-phenotype investigation of PBMCs and plasma/brain proteins provides a more sensitive biomarker exploratory platform than conventional case-control studies in a single matrix. The reported regulated proteins may represent novel biomarker candidates and potentially druggable targets.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_05:10:09.143.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterMichael Bremang
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListTMT6plex-126 reporter+balance reagent acylated residue; monohydroxylated residue; deamidated residue
InstrumentOrbitrap Fusion
Dataset History
RevisionDatetimeStatusChangeLog Entry
02020-07-22 00:43:11ID requested
12020-07-30 00:50:12announced
22024-10-22 05:10:11announced2024-10-22: Updated project metadata.
Publication List
Leoni E, Bremang M, Mitra V, Zubiri I, Jung S, Lu CH, Adiutori R, Lombardi V, Russell C, Koncarevic S, Ward M, Pike I, Malaspina A, Combined Tissue-Fluid Proteomics to Unravel Phenotypic Variability in Amyotrophic Lateral Sclerosis. Sci Rep, 9(1):4478(2019) [pubmed]
10.1038/s41598-019-40632-4;
Keyword List
submitter keyword: PBMC, ALS,TMT, TMTcalibrator
Contact List
Dr Ian Pike
contact affiliationProteome Sciences Plc., London
contact emailian.pike@proteomics.com
lab head
Michael Bremang
contact affiliationProteome Sciences
contact emailmichael.bremang@proteomics.com
dataset submitter
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Dataset FTP location
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PRIDE project URI
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