Dataset Information

SWATH-MS identification of CXCL7, LBP, TGFβ1 and PDGFRβ as novel biomarkers in human systemic mastocytosis.

ABSTRACT: We carried out a novel clinical biomarker investigation of the blood of systemic mastocytosis patients versus healthy controls; utilizing a new and emerging technology platform Sequential Window Acquisition of all Theoretical fragment-ion spectra mass spectrometry (SWATH-MS). This is the first use of this novel proteomic technique in the study of mastocytosis. A Swath-MS based biomarkers dsicovery study for systemic mastocytosis with orthogonal validation of biomarkers via ELISA.

INSTRUMENT(S): TripleTOF 6600

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Plasma

DISEASE(S): Systemic Mastocytosis

SUBMITTER: bobby graham

LAB HEAD: Dr Ciaren Graham

PROVIDER: PXD030947 | Pride | 2022-05-20

REPOSITORIES: Pride

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Publications

SWATH-MS identification of CXCL7, LBP, TGFβ1 and PDGFRβ as novel biomarkers in human systemic mastocytosis.

Graham R L J RLJ McMullen A A AA Moore G G Dempsey-Hibbert N C NC Myers B B Graham C C

Scientific reports 20220324 1

Mastocytosis is a rare myeloproliferative disease, characterised by accumulation of neoplastic mast cells in one or several organs. It presents as cutaneous or systemic. Patients with advanced systemic mastocytosis have a median survival of 3.5 years. The aetiology of mastocytosis is poorly understood, patients present with a broad spectrum of varying clinical symptoms that lack specificity to point clearly to a definitive diagnosis. Discovery of novel blood borne biomarkers would provide a trac ...[more]

PMID: 35332176

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Project description:Chronic lymphocytic leukaemia (CLL) is renowned for its variable clinical course and response to therapy, suggesting a role for precision medicine. However, the molecular basis of CLL variability remains incompletely understood. Recent developments in data independent acquisition (DIA) -MS technologies, such as SWATH (Sequential Windowed Acquisition of all THeoretical fragments), provide an opportunity to study the pathophysiology of CLL at the proteome level. This report describes the sample replication and data handling requirements for SWATH-MS analysis of clinical samples. A CLL-specific spectral library compromising over 1,500,000 spectra with digital information for over 150,000 peptides has been generated to enable the quantification of up to 7736 proteins. To assess the reproducibility of the assay, SWATH-MS analysis was performed on 6 cryopreserved CLL patient samples, incorporating biological (IGHV mutational status), sample preparation and MS technical replicates. Quantitative information was obtained for 5169 proteins (<1% FDR) across 54 SWATH-MS acquisitions. These analyses showed that SWATH-MS is a highly reproducible technique. However, replicate sample preparations on different days was identified as the main source of variation. To overcome the effect of variation between sample preparation batches, different computational approaches for batch correction were tested. All approaches successfully removed technical variability whilst retaining proteomic differences between clinical subgroups. Functional enrichment analysis of proteins associated to IGHV mutational status highlighted the importance of metabolic remodelling in the biology of CLL and overlapped significantly with previous studies based on gene expression profiling. Finally, an approach to perform statistical power analysis in proteomics studies was developed. This approach could be used to drive the design of future CLL SWATH-MS studies. These fundamental requirements for DIA approaches should be widely applicable to other clinical proteomics studies.

Dataset Information

SWATH-MS identification of CXCL7, LBP, TGFβ1 and PDGFRβ as novel biomarkers in human systemic mastocytosis.

Publications

SWATH-MS identification of CXCL7, LBP, TGFβ1 and PDGFRβ as novel biomarkers in human systemic mastocytosis.

Similar Datasets

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