Summary of Study ST002984
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001859. The data can be accessed directly via it's Project DOI: 10.21228/M8DT65 This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.
| Study ID | ST002984 |
| Study Title | Amino acid catabolite markers for early prognostication of pneumonia in patients with COVID-19 |
| Study Summary | Effective early-stage markers for predicting which patients are at risk of developing SARS-CoV-2 infection have not been fully investigated. Here, we performed comprehensive serum metabolome analysis of a total of 83 patients from two cohorts to determine that the acceleration of amino acid catabolism within 5 days from disease onset correlated with future disease severity. Increased levels of de-aminated amino acid catabolites involved in the de novo nucleotide synthesis pathway were identified as early prognostic markers that correlated with the initial viral load. We further employed mice models of SARS-CoV2-MA10 and influenza infection to demonstrate that such de-amination of amino acids and de novo synthesis of nucleotides were associated with the abnormal proliferation of airway and vascular tissue cells in the lungs during the early stages of infection. Consequently, it can be concluded that lung parenchymal tissue remodeling in the early stages of respiratory viral infections induces systemic metabolic remodeling and that the associated key amino acid catabolites are valid predictors for excessive inflammatory response in later disease stages. |
| Institute | Graduate School of Medicine, Kyoto University |
| Department | Center for Cancer Immunotherapy and Immunobiology |
| Laboratory | Sugiura-lab |
| Last Name | Sugiura |
| First Name | Yuki |
| Address | Shogoin-Kawaramachi 53,, Sakyo-ku, Kyoto, Kyoto, 160-8582, Japan |
| yuki.sgi@gmail.com | |
| Phone | +818050027858 |
| Submit Date | 2023-11-16 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | lcd, raw(Thermo) |
| Analysis Type Detail | LC-MS |
| Release Date | 2023-12-04 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Combined analysis:
| Analysis ID | AN004903 | AN004904 |
|---|---|---|
| Analysis type | MS | MS |
| Chromatography type | Ion exchange | Reversed phase |
| Chromatography system | Thermo Dionex ICS-5000+ | Shimadzu Nexera X2 |
| Column | Dionex IonPac AS11-HC (250 x 2mm, 4um) | Sigma-Aldrich Discovery HS F5-3 (150 x 2.1 mm, 3 um) |
| MS Type | ESI | ESI |
| MS instrument type | Orbitrap | Triple quadrupole |
| MS instrument name | Thermo Q Exactive Focus | LCMS-8060, Shimadzu Corporation |
| Ion Mode | UNSPECIFIED | UNSPECIFIED |
| Units | Peak area/Internal Standard | Peak area/Internal Standard |
Chromatography:
| Chromatography ID: | CH003698 |
| Chromatography Summary: | Metabolites were detected using an orbitrap-type MS instrument (Q-Exactive focus; Thermo Fisher Scientific) connected to a high-performance IC system (ICS-5000+, Thermo Fisher Scientific) that enabled highly selective and sensitive metabolite quantification owing to the IC separation and Fourier transfer MS principle. The IC instrument was equipped with an anion electrolytic suppressor (Dionex AERS 500; Thermo Fisher Scientific) to convert the potassium hydroxide gradient into pure water before the sample entered the MS instrument. Separation was performed using a Dionex IonPac AS11-HC 4 μm particle size column (Thermo Fisher Scientific). The IC flow rate was 0.25 mL/min, supplemented post-column with 0.18 mL/min makeup flow of MeOH. The potassium hydroxide gradient conditions for IC separation were as follows: from 1 mM to 100 mM (0–40 min) to 100 mM (40–50 min) and to 1 mM (50.1–60 min) at a column temperature of 30 °C. The mass spectrometer was operated in the ESI-positive and negative mode with polarity switching, for all detections. A full mass scan (m/z 70–900) was performed at a resolution of 70,000. The automatic gain control target was set at 3 × 106 ions, and the maximum ion injection time was 100 ms. The source ionization parameters were optimized with a spray voltage of 3 kV, and other parameters were as follows: transfer temperature, 320 °C; S-Lens level, 50; heater temperature, 300 °C; sheath gas, 36; and aux gas, 10. |
| Instrument Name: | Thermo Dionex ICS-5000+ |
| Column Name: | Dionex IonPac AS11-HC (250 x 2mm, 4um) |
| Column Temperature: | 30 °C |
| Flow Gradient: | From 1 mM to 100 mM (0–40 min) to 100 mM (40–50 min) and to 1 mM (50.1–60 min) |
| Flow Rate: | 0.25 mL/min, supplemented post-column with 0.18 mL/min makeup flow of MeOH |
| Solvent A: | The potassium hydroxide gradient conditions |
| Solvent B: | N/A |
| Chromatography Type: | Ion exchange |
| Chromatography ID: | CH003699 |
| Chromatography Summary: | Cationic metabolite concentrations were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). In essence, we employed a triple-quadrupole mass spectrometer equipped with an electrospray ionization (ESI) ion source (LCMS-8060, Shimadzu Corporation, Kyoto, Japan) operated in both positive and negative-ESI and in multiple reaction monitoring (MRM) modes. Analyte separation was achieved on a Discovery HS F5-3 column (2.1 mm I.D. × 150 mm L, 3 μm particle size; Sigma-Aldrich, St. Louis, MO, USA) through a gradient elution with mobile phase A (0.1% formate) and mobile phase B (0.1% acetonitrile). The elution profile was as follows: 100:0 (0–5 min), 75:25 (5–11 min), 65:35 (11–15 min), 5:95 (15–20 min), and 100:0 (20–25 min), with a constant flow rate of 0.25 mL/min and a column oven set at 40 °C. |
| Instrument Name: | Shimadzu Nexera X2 |
| Column Name: | Sigma-Aldrich Discovery HS F5-3 (150 x 2.1 mm, 3 um) |
| Column Temperature: | 40 °C |
| Flow Gradient: | 100:0 (0–5 min), 75:25 (5–11 min), 65:35 (11–15 min), 5:95 (15–20 min), and 100:0 (20–25 min) |
| Flow Rate: | 0.25 mL/min |
| Solvent A: | 0.1% formate |
| Solvent B: | acetonitrile with 0.1% formate |
| Chromatography Type: | Reversed phase |
