PXD020493 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Combined Tissue-Fluid Proteomics to Unravel Phenotypic Variability in Amyotrophic Lateral Sclerosis |
Description | The 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. |
HostingRepository | PRIDE |
AnnounceDate | 2024-10-22 |
AnnouncementXML | Submission_2024-10-22_05:10:09.143.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Michael Bremang |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | TMT6plex-126 reporter+balance reagent acylated residue; monohydroxylated residue; deamidated residue |
Instrument | Orbitrap Fusion |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2020-07-22 00:43:11 | ID requested | |
1 | 2020-07-30 00:50:12 | announced | |
⏵ 2 | 2024-10-22 05:10:11 | announced | 2024-10-22: 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 affiliation | Proteome Sciences Plc., London |
contact email | ian.pike@proteomics.com |
lab head | |
Michael Bremang |
contact affiliation | Proteome Sciences |
contact email | michael.bremang@proteomics.com |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD020493
- Label: PRIDE project
- Name: Combined Tissue-Fluid Proteomics to Unravel Phenotypic Variability in Amyotrophic Lateral Sclerosis