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Proteomic profiling of serum from patients with tuberculosis.

Song SH, Han M, Choi YS, Dan KS, Yang MG, Song J, Park SS, Lee JH - Ann Lab Med (2014)

Bottom Line: Peptides from alpha-1-antitrypsin and antithrombin III increased in TB patients and showed a high variable importance in the projection scores and coefficient in partial least square discriminant analysis.Sera from patients with TB had higher alpha-1-antitrypsin levels than sera from control participants.Alpha-1-antitrypsin levels may aid in the diagnosis of TB.

View Article: PubMed Central - PubMed

Affiliation: Clinical Proteomics Laboratory, Seoul National University Hospital, Seoul, Korea. ; Biomedical Research Institute and Department of Laboratory Medicine, Seoul National University Hospital, Seoul, Korea.

ABSTRACT

Background: Effective treatment and monitoring of tuberculosis (TB) requires biomarkers that can be easily evaluated in blood samples. The aim of this study was to analyze the serum proteome of patients with TB and to identify protein biomarkers for TB.

Methods: Serum samples from 26 TB patients and 31 controls were analyzed by using nano-flow ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry in data-independent mode, and protein and peptide amounts were calculated by using a label-free quantitative approach. The generated data were analyzed by using principal component analysis and partial least squares discriminant analysis, a multivariate statistical method.

Results: Of more than 500 proteins identified, alpha-1-antitrypsin was the most discriminative, which was 4.4 times higher in TB patients than in controls. Peptides from alpha-1-antitrypsin and antithrombin III increased in TB patients and showed a high variable importance in the projection scores and coefficient in partial least square discriminant analysis.

Conclusions: Sera from patients with TB had higher alpha-1-antitrypsin levels than sera from control participants. Alpha-1-antitrypsin levels may aid in the diagnosis of TB.

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Related in: MedlinePlus

PLS-DA of peptides from tuberculosis patients and controls. (A) The tuberculosis patients and controls were well separated on the score scatter plot, with some outliers and overlapping scores. (B) Most of the peptides clustered around the diagonal line of the plot. Proteins (black) close to the points representing the two groups (red) show the strongest correlation.Abbreviations: PLS-DA, partial least square-discriminant analysis; C, controls; P, tuberculosis patients.
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Figure 2: PLS-DA of peptides from tuberculosis patients and controls. (A) The tuberculosis patients and controls were well separated on the score scatter plot, with some outliers and overlapping scores. (B) Most of the peptides clustered around the diagonal line of the plot. Proteins (black) close to the points representing the two groups (red) show the strongest correlation.Abbreviations: PLS-DA, partial least square-discriminant analysis; C, controls; P, tuberculosis patients.

Mentions: Because fragmentation of tryptic peptides produces multiple types of peptides, such as peptides with missed cleavage, tryptic peptides shorter than expected, and peptides with modifications, the intensities of the different types of peptides from the expected large peptides were summed before statistical analysis. In total, 2,617 peptides were identified, and their amino acid sequences were used as identifiers. The five components from PLS-DA explained 27.8% of the variation of the X variable (peptides) and predicted 80.9% of the variation. The controls and TB patients were well separated on the score scatter plot (Fig. 2). The peptides identified in more than 70% of both controls and TB patients, with a P value less than 0.05 and a high rank of variable importance in the projection (VIP) score, are listed in Table 2. Of 18 peptides selected based on these criteria, 2 peptides were higher and 16 peptides were lower in TB patients than in controls. The two peptides that increased in TB patients were from alpha-1-antitrypsin (P01009) and antithrombin III (P01008). The 16 peptides that decreased in TB patients were from alpha-1-microglobulin (P02760), complement C3 (P01024), plasminogen (P00747), zinc alpha 2 glycoprotein (P25311), gelsolin (P06396), plasma protease C1 inhibitor (P05155), serum amyloid P component (P02743), inter-alpha-trypsin inhibitor heavy chain H4 and H1 (Q14624 and P19827), complement C4 (P0C0L4), and hemopexin (P02790).


Proteomic profiling of serum from patients with tuberculosis.

Song SH, Han M, Choi YS, Dan KS, Yang MG, Song J, Park SS, Lee JH - Ann Lab Med (2014)

PLS-DA of peptides from tuberculosis patients and controls. (A) The tuberculosis patients and controls were well separated on the score scatter plot, with some outliers and overlapping scores. (B) Most of the peptides clustered around the diagonal line of the plot. Proteins (black) close to the points representing the two groups (red) show the strongest correlation.Abbreviations: PLS-DA, partial least square-discriminant analysis; C, controls; P, tuberculosis patients.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4151002&req=5

Figure 2: PLS-DA of peptides from tuberculosis patients and controls. (A) The tuberculosis patients and controls were well separated on the score scatter plot, with some outliers and overlapping scores. (B) Most of the peptides clustered around the diagonal line of the plot. Proteins (black) close to the points representing the two groups (red) show the strongest correlation.Abbreviations: PLS-DA, partial least square-discriminant analysis; C, controls; P, tuberculosis patients.
Mentions: Because fragmentation of tryptic peptides produces multiple types of peptides, such as peptides with missed cleavage, tryptic peptides shorter than expected, and peptides with modifications, the intensities of the different types of peptides from the expected large peptides were summed before statistical analysis. In total, 2,617 peptides were identified, and their amino acid sequences were used as identifiers. The five components from PLS-DA explained 27.8% of the variation of the X variable (peptides) and predicted 80.9% of the variation. The controls and TB patients were well separated on the score scatter plot (Fig. 2). The peptides identified in more than 70% of both controls and TB patients, with a P value less than 0.05 and a high rank of variable importance in the projection (VIP) score, are listed in Table 2. Of 18 peptides selected based on these criteria, 2 peptides were higher and 16 peptides were lower in TB patients than in controls. The two peptides that increased in TB patients were from alpha-1-antitrypsin (P01009) and antithrombin III (P01008). The 16 peptides that decreased in TB patients were from alpha-1-microglobulin (P02760), complement C3 (P01024), plasminogen (P00747), zinc alpha 2 glycoprotein (P25311), gelsolin (P06396), plasma protease C1 inhibitor (P05155), serum amyloid P component (P02743), inter-alpha-trypsin inhibitor heavy chain H4 and H1 (Q14624 and P19827), complement C4 (P0C0L4), and hemopexin (P02790).

Bottom Line: Peptides from alpha-1-antitrypsin and antithrombin III increased in TB patients and showed a high variable importance in the projection scores and coefficient in partial least square discriminant analysis.Sera from patients with TB had higher alpha-1-antitrypsin levels than sera from control participants.Alpha-1-antitrypsin levels may aid in the diagnosis of TB.

View Article: PubMed Central - PubMed

Affiliation: Clinical Proteomics Laboratory, Seoul National University Hospital, Seoul, Korea. ; Biomedical Research Institute and Department of Laboratory Medicine, Seoul National University Hospital, Seoul, Korea.

ABSTRACT

Background: Effective treatment and monitoring of tuberculosis (TB) requires biomarkers that can be easily evaluated in blood samples. The aim of this study was to analyze the serum proteome of patients with TB and to identify protein biomarkers for TB.

Methods: Serum samples from 26 TB patients and 31 controls were analyzed by using nano-flow ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry in data-independent mode, and protein and peptide amounts were calculated by using a label-free quantitative approach. The generated data were analyzed by using principal component analysis and partial least squares discriminant analysis, a multivariate statistical method.

Results: Of more than 500 proteins identified, alpha-1-antitrypsin was the most discriminative, which was 4.4 times higher in TB patients than in controls. Peptides from alpha-1-antitrypsin and antithrombin III increased in TB patients and showed a high variable importance in the projection scores and coefficient in partial least square discriminant analysis.

Conclusions: Sera from patients with TB had higher alpha-1-antitrypsin levels than sera from control participants. Alpha-1-antitrypsin levels may aid in the diagnosis of TB.

Show MeSH
Related in: MedlinePlus