Dataset Information

Application of Multiplexed Ion Mobility Spectrometry towards the Identification of Host Protein Signatures of Treatment Effect in Pulmonary Tuberculosis

ABSTRACT: Utilized sensitive, high throughput multiplexed ion mobility-mass spectrometry (IM-MS) to characterize the serum proteome of tuberculosis patients prior to and at 8 weeks of antibiotic treatment. Goal is to identify a serum protein signature indicative of treatment effect.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Serum

DISEASE(S): Pulmonary Tuberculosis

SUBMITTER: Matthew Monroe

LAB HEAD: Payam Nahid

PROVIDER: PXD009029 | Pride | 2018-10-19

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	TB_Pool2_Baseline_01_2_9Jan14_Samwise_13-07-28.mgf	Mgf
	TB_Pool2_Baseline_01_2_9Jan14_Samwise_13-07-28.pride.mgf.gz	Mgf
	TB_Pool2_Baseline_01_2_9Jan14_Samwise_13-07-28.raw	Raw
	TB_Pool2_Baseline_01_2_9Jan14_Samwise_13-07-28_msgfplus.mzid.gz	Mzid
	TB_Pool2_Baseline_01_2_9Jan14_Samwise_13-07-28_msgfplus.pride.mztab.gz	Mztab

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Publications

Application of multiplexed ion mobility spectrometry towards the identification of host protein signatures of treatment effect in pulmonary tuberculosis.

Kedia Komal K Wendler Jason P JP Baker Erin S ES Burnum-Johnson Kristin E KE Jarsberg Leah G LG Stratton Kelly G KG Wright Aaron T AT Piehowski Paul D PD Gritsenko Marina A MA Lewinsohn David M DM Sigal George B GB Weiner Marc H MH Smith Richard D RD Jacobs Jon M JM Nahid Payam P

Tuberculosis (Edinburgh, Scotland) 20180718

<h4>Rationale</h4>The monitoring of TB treatments in clinical practice and clinical trials relies on traditional sputum-based culture status indicators at specific time points. Accurate, predictive, blood-based protein markers would provide a simpler and more informative view of patient health and response to treatment.<h4>Objective</h4>We utilized sensitive, high throughput multiplexed ion mobility-mass spectrometry (IM-MS) to characterize the serum proteome of TB patients at the start of and a ...[more]

PMID: 30205969

Similar Datasets

Project description:RationaleThe monitoring of TB treatments in clinical practice and clinical trials relies on traditional sputum-based culture status indicators at specific time points. Accurate, predictive, blood-based protein markers would provide a simpler and more informative view of patient health and response to treatment.ObjectiveWe utilized sensitive, high throughput multiplexed ion mobility-mass spectrometry (IM-MS) to characterize the serum proteome of TB patients at the start of and at 8 weeks of rifamycin-based treatment. We sought to identify treatment specific signatures within patients as well as correlate the proteome signatures to various clinical markers of treatment efficacy.MethodsSerum samples were collected from 289 subjects enrolled in CDC TB Trials Consortium Study 29 at time of enrollment and at the end of the intensive phase (after 40 doses of TB treatment). Serum proteins were immunoaffinity-depleted of high abundant components, digested to peptides and analyzed for data acquisition utilizing a unique liquid chromatography IM-MS platform (LC-IM-MS). Linear mixed models were utilized to identify serum protein changes in the host response to antibiotic treatment as well as correlations with culture status end points.ResultsA total of 10,137 peptides corresponding to 872 proteins were identified, quantified, and used for statistical analysis across the longitudinal patient cohort. In response to TB treatment, 244 proteins were significantly altered. Pathway/network comparisons helped visualize the interconnected proteins, identifying up regulated (lipid transport, coagulation cascade, endopeptidase activity) and down regulated (acute phase) processes and pathways in addition to other cross regulated networks (inflammation, cell adhesion, extracellular matrix). Detection of possible lung injury serum proteins such as HPSE, significantly downregulated upon treatment. Analyses of microbiologic data over time identified a core set of serum proteins (TTHY, AFAM, CRP, RET4, SAA1, PGRP2) which change in response to treatment and also strongly correlate with culture status. A similar set of proteins at baseline were found to be predictive of week 6 and 8 culture status.ConclusionA comprehensive host serum protein dataset reflective of TB treatment effect is defined. A repeating set of serum proteins (TTHY, AFAM, CRP, RET4, SAA1, PGRP2, among others) were found to change significantly in response to treatment, to strongly correlate with culture status, and at baseline to be predictive of future culture conversion. If validated in cohorts with long term follow-up to capture failure and relapse of TB, these protein markers could be developed for monitoring of treatment in clinical trials and in patient care.