Summary of Study ST002955
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 PR001838. The data can be accessed directly via it's Project DOI: 10.21228/M84H8B 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 | ST002955 |
| Study Title | Untargeted metabolomics analysis of plasma from viremic non-progressors (VNP), progressors, and healthy control (HC) patients using high-resolution, high-performance LC-MS/MS analysis. |
| Study Summary | Viremic Non-Progressors (VNPs) maintain normal CD4+ T-cell counts despite uncontrolled HIV-1 replication, but mechanisms leading to CD4+ T-cell preservation are incompletely characterized. We aim to generate a comprehensive understanding of this infrequent phenotype by comparing rates of cellular infection, immunophenotype, genomics, single-cell transcriptomics, metabolomics, and levels of plasma biomarkers in 16 VNPs and 29 HIV+ Progressors. During chronic infection VNPs show lower frequency of HIV-1-infected cells in periphery, which is associated with reduced CCR5 expression and higher prevalence of CCR5Δ32 heterozygosity. The CD8+ T-cell compartment displays a less cytotoxic and less activated phenotype in VNPs. Moreover, despite similar viremia, we found lower bystander CD4+ T-cell death in the VNPs, together with weaker IFN responses, reduced plasma levels of zonulin (a biomarker of intestinal permeability), altered tryptophan catabolism, and preserved LPS responsiveness in vitro. Overall, a complex multifactorial mechanism, suggesting gut-associated lymphoid tissue preservation, underlies resistance to HIV pathogenesis in VNPs. |
| Institute | IrsiCaixa |
| Last Name | Martinez-Picado |
| First Name | Javier |
| Address | Carretera de Canyet, s/n, 08916 Badalona, Barcelona |
| jmpicado@irsicaixa.es | |
| Phone | +34 934 65 63 74 |
| Submit Date | 2023-11-02 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | raw(Thermo) |
| Analysis Type Detail | LC-MS |
| Release Date | 2024-10-16 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Project:
| Project ID: | PR001838 |
| Project DOI: | doi: 10.21228/M84H8B |
| Project Title: | Viremic non-progressors evade HIV-1 pathogenesis by CCR5Δ32 heterozygosity, low activation of cytotoxic cells and reduced IFN response |
| Project Summary: | Viremic Non-Progressors (VNPs) maintain normal CD4+ T-cell counts despite uncontrolled HIV-1 replication, but mechanisms leading to CD4+ T-cell preservation are incompletely characterized. We aim to generate a comprehensive understanding of this infrequent phenotype by comparing rates of cellular infection, immunophenotype, genomics, single-cell transcriptomics, metabolomics, and levels of plasma biomarkers in 16 VNPs and 29 HIV+ Progressors. During chronic infection VNPs show lower frequency of HIV-1-infected cells in periphery, which is associated with reduced CCR5 expression and higher prevalence of CCR5Δ32 heterozygosity. The CD8+ T-cell compartment displays a less cytotoxic and less activated phenotype in VNPs. Moreover, despite similar viremia, we found lower bystander CD4+ T-cell death in the VNPs, together with weaker IFN responses, reduced plasma levels of zonulin (a biomarker of intestinal permeability), altered tryptophan catabolism, and preserved LPS responsiveness in vitro. Overall, a complex multifactorial mechanism, suggesting gut-associated lymphoid tissue preservation, underlies resistance to HIV pathogenesis in VNPs. |
| Institute: | IrsiCaixa |
| Last Name: | Martinez-Picado |
| First Name: | Javier |
| Address: | Carretera de Canyet, s/n, 08916 Badalona, Barcelona |
| Email: | jmpicado@irsicaixa.es |
| Phone: | +34 934 65 63 74 |
Subject:
| Subject ID: | SU003068 |
| Subject Type: | Human |
| Subject Species: | Homo sapiens |
| Taxonomy ID: | 9606 |
Factors:
Subject type: Human; Subject species: Homo sapiens (Factor headings shown in green)
| mb_sample_id | local_sample_id | Group |
|---|---|---|
| SA321855 | 8 | HC |
| SA321856 | 20 | HC |
| SA321857 | 29 | HC |
| SA321858 | 40 | HC |
| SA321859 | 38 | HC |
| SA321860 | 44 | HC |
| SA321901 | QC-12 | n/a |
| SA321902 | QC-11 | n/a |
| SA321903 | QC-9 | n/a |
| SA321904 | QC-8 | n/a |
| SA321905 | QC-10 | n/a |
| SA321861 | 27 | Progressor |
| SA321862 | 28 | Progressor |
| SA321863 | 1 | Progressor |
| SA321864 | 45 | Progressor |
| SA321865 | 25 | Progressor |
| SA321866 | 22 | Progressor |
| SA321867 | 31 | Progressor |
| SA321868 | 43 | Progressor |
| SA321869 | 39 | Progressor |
| SA321870 | 36 | Progressor |
| SA321871 | 34 | Progressor |
| SA321872 | 42 | Progressor |
| SA321873 | 26 | Progressor |
| SA321874 | 7 | Progressor |
| SA321875 | 10 | Progressor |
| SA321876 | 12 | Progressor |
| SA321877 | 6 | Progressor |
| SA321878 | 5 | Progressor |
| SA321879 | 3 | Progressor |
| SA321880 | 4 | Progressor |
| SA321881 | 14 | Progressor |
| SA321882 | 11 | Progressor |
| SA321883 | 17 | Progressor |
| SA321884 | 19 | Progressor |
| SA321885 | 15 | Progressor |
| SA321886 | 18 | VNP |
| SA321887 | 30 | VNP |
| SA321888 | 24 | VNP |
| SA321889 | 23 | VNP |
| SA321890 | 2 | VNP |
| SA321891 | 46 | VNP |
| SA321892 | 41 | VNP |
| SA321893 | 33 | VNP |
| SA321894 | 9 | VNP |
| SA321895 | 13 | VNP |
| SA321896 | 35 | VNP |
| SA321897 | 32 | VNP |
| SA321898 | 21 | VNP |
| SA321899 | 16 | VNP |
| SA321900 | 37 | VNP |
| Showing results 1 to 51 of 51 |
Collection:
| Collection ID: | CO003061 |
| Collection Summary: | Blood samples from HIV+ VNPs and Progressors were collected in EDTA-treated tubes and plasma fraction was isolated by centrifugation at University Hospital Germans Trias i Pujol (Barcelona, Spain). Blood samples from HIV seronegative individuals were collected in EDTA-treated tubes and plasma fraction was isolated by centrifugation at The Wistar Institute (Philadelphia, US). |
| Sample Type: | Blood (plasma) |
Treatment:
| Treatment ID: | TR003077 |
| Treatment Summary: | No treatment was applied. Inclusion criteria for each group were as follows: HC - HIV seronegative; VNP - viral load > 10,000 copies/ml and CD4 T-cell decay rate < 10% for a minimum of 4 years of ART-free follow-up; Progressor - viral load > 10,000 copies/ml and CD4 T-cell decay rate > 10%. |
Sample Preparation:
| Sampleprep ID: | SP003074 |
| Sampleprep Summary: | Briefly, polar metabolites were extracted from 50 µl plasma samples with 500 µl of ice-cold 80:20 (v/v) methanol/water spiked with 1.5 µM heavy-labeled amino acid internal standard mix. Deproteinated supernatants were stored at −80 °C prior to analysis. A quality control (QC) pool sample was made by pooling a small aliquot from each sample extract. |
| Processing Storage Conditions: | -80℃ |
| Extract Storage: | -80℃ |
Combined analysis:
| Analysis ID | AN004852 |
|---|---|
| Analysis type | MS |
| Chromatography type | HILIC |
| Chromatography system | Thermo Vanquish Horizon UHPLC |
| Column | SeQuant ZIC- pHILIC (150 x 2.1mm,5um) |
| MS Type | ESI |
| MS instrument type | Orbitrap |
| MS instrument name | Thermo Q Exactive HF-X Orbitrap |
| Ion Mode | UNSPECIFIED |
| Units | Peak Area |
Chromatography:
| Chromatography ID: | CH003663 |
| Chromatography Summary: | Hydrophilic interaction liquid chromatography (HILIC) was performed at 0.2 ml/min on a ZIC-pHILIC column (2.1 mm × 150 mm, EMD Millipore) at 45 °C. Solvent A was 20 mM ammonium carbonate, 5 µM medronic acid, 0.1% ammonium hydroxide, pH 9.2, and solvent B was acetonitrile. The gradient was 85% B for 2 min, 85% B to 20% B over 15 min, 20% B to 85% B over 0.1 min, and 85% B for 8.9 min. The autosampler was held at 4 °C. For each analysis, 4 µl of sample was injected. |
| Instrument Name: | Thermo Vanquish Horizon UHPLC |
| Column Name: | SeQuant ZIC- pHILIC (150 x 2.1mm,5um) |
| Column Temperature: | 45 |
| Flow Gradient: | 85% B for 2 min, 85% B to 20% B over 15 min, 20% B to 85% B over 0.1 min, and 85% B for 8.9 min |
| Flow Rate: | 0.2 ml/min |
| Solvent A: | 100% water; 20 mM ammonium carbonate; 5 µM medronic acid; 0.1% ammonium hydroxide, pH 9.2 |
| Solvent B: | 100% acetonitrile |
| Chromatography Type: | HILIC |
MS:
| MS ID: | MS004597 |
| Analysis ID: | AN004852 |
| Instrument Name: | Thermo Q Exactive HF-X Orbitrap |
| Instrument Type: | Orbitrap |
| MS Type: | ESI |
| MS Comments: | The following parameters were used for the MS analysis: sheath gas flow rate, 40; auxiliary gas flow rate, 10; sweep gas flow rate, 2; auxiliary gas heater temperature, 350 °C; spray voltage, 3.5 kV for positive mode and 3.2 kV for negative mode; capillary temperature, 325 °C; and funnel RF level, 40. All samples were analyzed by full MS with polarity switching. The QC sample was analyzed at the start of the sample sequence and after every 3-4 samples. The QC sample was also analyzed by data-dependent MS/MS with separate runs for positive and negative ion modes. Full MS scans were acquired at 120,000 resolution with a scan range of 65-975 m/z. Data-dependent MS/MS scans were acquired for the top 10 highest intensity ions at 15,000 resolution with an isolation width of 1.0 m/z and stepped normalized collision energy of 20-40-60. Data analysis was performed using Compound Discoverer 3.3 SP1 (Thermo Fisher Scientific) with separate analyses for positive and negative polarities. Retention time alignment used the adaptative curve model with 0.3 min maximum shift, 5 ppm mass tolerance, and 3 S/N threshold. Peak detection required less than 5 ppm mass error for extracted ion chromatograms with a 100,000 minimum peak intensity. [M+H]+1 and [M-H]-1 adducts were considered. Peaks were required to have a width at half height less than 1.0 min and a minimum of 5 scans. Components that had only a monoisotopic peak and no further isotopes were discarded. The maximum element count for isotope pattern modeling was C90H190N10O20P3S5. Compounds were grouped across samples with 5 ppm mass error and 0.2 min retention time shift. Peaks not detected initially in a given sample were determined using the fill gaps algorithm with 5 ppm mass error and 1.5 S/N threshold with real peak detection. The gap function uses a priority system to determine missing values: 1) matching detected ions based on expected m/z and retention time regardless of adduct assignment, 2) re-detecting peaks at lower thresholds, 3) simulating peaks based on expected m/z, and 4) imputing spectrum noise based on detection limit values. Compound quantifications were corrected for instrument drift by QC areas using the cubic spline regression model. Values were further normalized to the summed area of identified and filtered metabolites in each sample. Each compound was required to be detected in all QC runs with an RSD less than 40%. Metabolites were identified by accurate mass (5 ppm mass error) and retention time (0.3 min shift) using a database generated from pure standards or by accurate mass and MS/MS spectra using the mzCloud spectral database (mzCloud.org) and selecting the best matches with HighChem HighRes identity search match factors of 50 or greater. Results were manually processed to remove entries with apparent peak mis-integrations and correct commonly misannotated metabolites. Positive and negative data sets of identified compounds were merged, and the preferred polarity was selected for compounds identified in both polarities. For compounds identified multiple times at different retention times, a single entry was selected with priority given to standards database matches followed by greater mzCloud match factors and peak areas. |
| Ion Mode: | UNSPECIFIED |
