PXD034596

PXD034596 is an original dataset announced via ProteomeXchange.

Title	Proteomic profiling of fibroblasts differentiates patients with severe, intermediate and mild spinal muscular atrophy
Description	Most research to characterise the molecular consequences of spinal muscular atrophy (SMA) have focused on SMA I. Here, proteomic profiling of skin fibroblasts from severe (SMA I), intermediate (SMA II), or mild (SMA III) patients and age-matched controls was conducted using SWATH mass spectrometry analysis. Differentially expressed proteome profiles showed limited overlap across each SMA type, and variability was greatest within SMA II fibroblasts which was not explained by SMN2 copy number. Despite limited proteomic overlap, enriched canonical pathways common to all SMA types included mTOR signaling, regulation of eIF2 and eIF4 signaling, and protein ubiquitination. BioLayout expression clustering identified protein profiles that discriminate or correlate with SMA severity. From these clusters, the differential expression of PYGB (SMA I), RAB3B (SMA II), and IMP1 and STAT1 (both SMA III) was verified by western blot, and transfection of SMA II fibroblasts with SMN-enhanced constructs confirmed RAB3B expression is SMN-dependent. In combination, this four-protein panel may have potential utility for stratifying patients into clinical trials or for monitoring therapeutic effectiveness. In addition, the diverse proteome profiles and pathways identified here pave the way for further studies aimed at optimising therapeutic strategies for SMA patients of differing severities.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:56:22.560.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Sally Shirran
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	TripleTOF 5600

Revision	Datetime	Status	ChangeLog Entry
0	2022-06-16 03:38:09	ID requested
1	2022-08-24 02:55:52	announced
⏵ 2	2023-11-14 08:56:23	announced	2023-11-14: Updated project metadata.

Dataset with its publication pending

submitter keyword: proteomic profile,spinal muscular atrophy

Heidi Fuller
contact affiliation	Wolfson Centre for Inherited Neuromuscular Disease, TORCH Building, RJAH Orthopaedic Hospital, Oswestry, SY10 7AG, UK
contact email	h.r.fuller@keele.ac.uk
lab head
Sally Shirran
contact affiliation	University of St Andrews
contact email	ss101@st-andrews.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD034596
     1. Label: PRIDE project
     2. Name: Proteomic profiling of fibroblasts differentiates patients with severe, intermediate and mild spinal muscular atrophy