Summary of Study ST003520
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 PR002165. The data can be accessed directly via it's Project DOI: 10.21228/M8S247 This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
Study ID | ST003520 |
Study Title | Identification of Plasma Metabolomic Biomarkers of Juvenile Idiopathic Arthritis |
Study Type | Clinical |
Study Summary | This study utilizes plasma metabolomic profiling to identify biomarkers associated with juvenile idiopathic arthritis (JIA) by analyzing samples from treatment-naïve JIA patients and non-JIA controls. Significant metabolic alterations were detected, with sphingosine metabolites and fatty acid ethanolamides showing notable increases in JIA patients, while specific compounds such as sarcosine were decreased. The research highlights 11 highly discriminatory metabolites, including sphinganine-1-phosphate, demonstrating potential for improved JIA diagnosis and treatment through targeted metabolic profiling. |
Institute | University of Kansas |
Department | Center for Computational Biology |
Laboratory | Funk |
Last Name | Kumar |
First Name | Amar |
Address | Multidisciplinary Research Bldg. 2030 Becker Drive Lawrence, KS 66047 |
amarkumar@ku.edu | |
Phone | 18723016225 |
Submit Date | 2024-09-09 |
Num Groups | 2 |
Total Subjects | 210 |
Num Males | 82 |
Num Females | 128 |
Study Comments | Although the raw dataset initially included 210 subjects, only 207 were included in the final analysis due to consent-related exclusions. These three subjects were removed to ensure compliance with ethical standards. |
Analysis Type Detail | LC-MS |
Release Date | 2024-11-01 |
Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Project:
Project ID: | PR002165 |
Project DOI: | doi: 10.21228/M8S247 |
Project Title: | Identification of Plasma Metabolomic Biomarkers of Juvenile Idiopathic Arthritis |
Project Type: | Clinical |
Project Summary: | The identification of reliable disease and therapeutic biomarkers remains a significant challenge for early diagnosis and the initiation of effective disease-modifying therapies in juvenile idiopathic arthritis (JIA). In this study, comprehensive plasma metabolomic profiling was conducted to elucidate metabolic biomarkers associated with JIA pathophysiology. |
Institute: | University of Kansas |
Department: | Center for Computational Biology |
Laboratory: | Funk |
Last Name: | Kumar |
First Name: | Amar |
Address: | Multidisciplinary Research Bldg. 2030 Becker Drive, Lawrence, KS 66047 |
Email: | amarkumar@ku.edu |
Phone: | 18723016225 |
Subject:
Subject ID: | SU003649 |
Subject Type: | Human |
Subject Species: | Homo sapiens |
Taxonomy ID: | 9606 |
Age Or Age Range: | 1.50–20.33 years |
Gender: | Male and female |
Species Group: | Mammals |
Factors:
Subject type: Human; Subject species: Homo sapiens (Factor headings shown in green)
mb_sample_id | local_sample_id | Sample source | Group |
---|---|---|---|
SA386516 | UKAN-00680 | EDTA plasma | Crohn's Disease |
SA386517 | UKAN-00636 | EDTA plasma | Crohn's Disease |
SA386518 | UKAN-00637 | EDTA plasma | Crohn's Disease |
SA386519 | UKAN-00642 | EDTA plasma | Crohn's Disease |
SA386520 | UKAN-00643 | EDTA plasma | Crohn's Disease |
SA386521 | UKAN-00645 | EDTA plasma | Crohn's Disease |
SA386522 | UKAN-00670 | EDTA plasma | Crohn's Disease |
SA386523 | UKAN-00671 | EDTA plasma | Crohn's Disease |
SA386524 | UKAN-00674 | EDTA plasma | Crohn's Disease |
SA386525 | UKAN-00675 | EDTA plasma | Crohn's Disease |
SA386526 | UKAN-00677 | EDTA plasma | Crohn's Disease |
SA386527 | UKAN-00683 | EDTA plasma | Crohn's Disease |
SA386528 | UKAN-00633 | EDTA plasma | Crohn's Disease |
SA386529 | UKAN-00684 | EDTA plasma | Crohn's Disease |
SA386530 | UKAN-00686 | EDTA plasma | Crohn's Disease |
SA386531 | UKAN-00710 | EDTA plasma | Crohn's Disease |
SA386532 | UKAN-00714 | EDTA plasma | Crohn's Disease |
SA386533 | UKAN-00715 | EDTA plasma | Crohn's Disease |
SA386534 | UKAN-00716 | EDTA plasma | Crohn's Disease |
SA386535 | UKAN-00721 | EDTA plasma | Crohn's Disease |
SA386536 | UKAN-00723 | EDTA plasma | Crohn's Disease |
SA386537 | UKAN-00724 | EDTA plasma | Crohn's Disease |
SA386538 | UKAN-00725 | EDTA plasma | Crohn's Disease |
SA386539 | UKAN-00635 | EDTA plasma | Crohn's Disease |
SA386540 | UKAN-00712 | EDTA plasma | Crohn's Disease |
SA386541 | UKAN-00631 | EDTA plasma | Crohn's Disease |
SA386542 | UKAN-00632 | EDTA plasma | Healthy_Control |
SA386543 | UKAN-00827 | EDTA plasma | Healthy_Control |
SA386544 | UKAN-00708 | EDTA plasma | Healthy_Control |
SA386545 | UKAN-00707 | EDTA plasma | Healthy_Control |
SA386546 | UKAN-00822 | EDTA plasma | Healthy_Control |
SA386547 | UKAN-00823 | EDTA plasma | Healthy_Control |
SA386548 | UKAN-00824 | EDTA plasma | Healthy_Control |
SA386549 | UKAN-00825 | EDTA plasma | Healthy_Control |
SA386550 | UKAN-00826 | EDTA plasma | Healthy_Control |
SA386551 | UKAN-00829 | EDTA plasma | Healthy_Control |
SA386552 | UKAN-00828 | EDTA plasma | Healthy_Control |
SA386553 | UKAN-00711 | EDTA plasma | Healthy_Control |
SA386554 | UKAN-00830 | EDTA plasma | Healthy_Control |
SA386555 | UKAN-00831 | EDTA plasma | Healthy_Control |
SA386556 | UKAN-00832 | EDTA plasma | Healthy_Control |
SA386557 | UKAN-00833 | EDTA plasma | Healthy_Control |
SA386558 | UKAN-00685 | EDTA plasma | Healthy_Control |
SA386559 | UKAN-00682 | EDTA plasma | Healthy_Control |
SA386560 | UKAN-00681 | EDTA plasma | Healthy_Control |
SA386561 | UKAN-00709 | EDTA plasma | Healthy_Control |
SA386562 | UKAN-00717 | EDTA plasma | Healthy_Control |
SA386563 | UKAN-00713 | EDTA plasma | Healthy_Control |
SA386564 | UKAN-00801 | EDTA plasma | Healthy_Control |
SA386565 | UKAN-00793 | EDTA plasma | Healthy_Control |
SA386566 | UKAN-00794 | EDTA plasma | Healthy_Control |
SA386567 | UKAN-00795 | EDTA plasma | Healthy_Control |
SA386568 | UKAN-00796 | EDTA plasma | Healthy_Control |
SA386569 | UKAN-00797 | EDTA plasma | Healthy_Control |
SA386570 | UKAN-00798 | EDTA plasma | Healthy_Control |
SA386571 | UKAN-00799 | EDTA plasma | Healthy_Control |
SA386572 | UKAN-00800 | EDTA plasma | Healthy_Control |
SA386573 | UKAN-00802 | EDTA plasma | Healthy_Control |
SA386574 | UKAN-00678 | EDTA plasma | Healthy_Control |
SA386575 | UKAN-00803 | EDTA plasma | Healthy_Control |
SA386576 | UKAN-00804 | EDTA plasma | Healthy_Control |
SA386577 | UKAN-00726 | EDTA plasma | Healthy_Control |
SA386578 | UKAN-00634 | EDTA plasma | Healthy_Control |
SA386579 | UKAN-00722 | EDTA plasma | Healthy_Control |
SA386580 | UKAN-00720 | EDTA plasma | Healthy_Control |
SA386581 | UKAN-00719 | EDTA plasma | Healthy_Control |
SA386582 | UKAN-00718 | EDTA plasma | Healthy_Control |
SA386583 | UKAN-00679 | EDTA plasma | Healthy_Control |
SA386584 | UKAN-00834 | EDTA plasma | Healthy_Control |
SA386585 | UKAN-00853 | EDTA plasma | Healthy_Control |
SA386586 | UKAN-00864 | EDTA plasma | Healthy_Control |
SA386587 | UKAN-00854 | EDTA plasma | Healthy_Control |
SA386588 | UKAN-00676 | EDTA plasma | Healthy_Control |
SA386589 | UKAN-00852 | EDTA plasma | Healthy_Control |
SA386590 | UKAN-00856 | EDTA plasma | Healthy_Control |
SA386591 | UKAN-00857 | EDTA plasma | Healthy_Control |
SA386592 | UKAN-00858 | EDTA plasma | Healthy_Control |
SA386593 | UKAN-00859 | EDTA plasma | Healthy_Control |
SA386594 | UKAN-00860 | EDTA plasma | Healthy_Control |
SA386595 | UKAN-00861 | EDTA plasma | Healthy_Control |
SA386596 | UKAN-00862 | EDTA plasma | Healthy_Control |
SA386597 | UKAN-00855 | EDTA plasma | Healthy_Control |
SA386598 | UKAN-00646 | EDTA plasma | Healthy_Control |
SA386599 | UKAN-00863 | EDTA plasma | Healthy_Control |
SA386600 | UKAN-00667 | EDTA plasma | Healthy_Control |
SA386601 | UKAN-00668 | EDTA plasma | Healthy_Control |
SA386602 | UKAN-00630 | EDTA plasma | Healthy_Control |
SA386603 | UKAN-00629 | EDTA plasma | Healthy_Control |
SA386604 | UKAN-00638 | EDTA plasma | Healthy_Control |
SA386605 | UKAN-00673 | EDTA plasma | Healthy_Control |
SA386606 | UKAN-00639 | EDTA plasma | Healthy_Control |
SA386607 | UKAN-00640 | EDTA plasma | Healthy_Control |
SA386608 | UKAN-00672 | EDTA plasma | Healthy_Control |
SA386609 | UKAN-00641 | EDTA plasma | Healthy_Control |
SA386610 | UKAN-00628 | EDTA plasma | Healthy_Control |
SA386611 | UKAN-00627 | EDTA plasma | Healthy_Control |
SA386612 | UKAN-00644 | EDTA plasma | Healthy_Control |
SA386613 | UKAN-00669 | EDTA plasma | Healthy_Control |
SA386614 | UKAN-00808 | EDTA plasma | JIA |
SA386615 | UKAN-00809 | EDTA plasma | JIA |
Collection:
Collection ID: | CO003642 |
Collection Summary: | EDTA (Ethylenediaminetetraacetic acid) plasma specimens were systematically harvested from distinct patient cohorts under uniform preservative protocols and collection methodologies, although executed across disparate facilities by varying technical staff. The bio-samples involved two primary groups: patients diagnosed with Juvenile Idiopathic Arthritis (JIA) prior to the initiation of disease-modifying antirheumatic drugs (DMARDs), and a reference non-JIA pediatric population including children with active Crohn’s disease and healthy controls without autoimmune or discernible gastrointestinal or rheumatologic pathology. For JIA, plasma samples were procured in two phases: the discovery cohort consisting of 60 subjects from Children’s Mercy Kansas City (CM-KC), and the replication cohort comprising 49 subjects enrolled through PROMOTE studies at both CM-KC and Cincinnati Children’s Hospital Medical Center (CCHMC), Ohio. The non-JIA samples (n = 98) were sourced from a biorepository at CM-KC, collected in a fasted state during morning hours (7:30–11:30 A.M.), and were all from subjects who were age-matched to the JIA group and showed no organic causes for gastrointestinal symptoms, including no significant findings on histopathology from tissues biopsied during endoscopy. All specimens at CM-KC were gathered from subjects who had fasted for at least 8 hours, ensuring consistency in sample conditions. Patients provided age-appropriate informed consent or assent, and all sample collections were conducted under IRB-approved protocols to uphold ethical standards in research. Upon receiving, the venous blood samples were centrifuged using a Beckman tabletop centrifuge at 2000 RPM for 10 minutes to separate plasma. The resultant plasma supernatant was then aliquoted and preserved at -80°C. Prior to undergoing global metabolomic analysis, these samples were shipped on dry ice. Please note that for the analysis, both the datasets were combined into one dataset i.e., merged dataset, for more information please refer to the manuscript. DOI : https://doi.org/10.3390/metabo14090499 |
Sample Type: | Blood (plasma) |
Storage Conditions: | -80℃ |
Treatment:
Treatment ID: | TR003658 |
Treatment Summary: | None |
Sample Preparation:
Sampleprep ID: | SP003656 |
Sampleprep Summary: | Samples were thawed on ice prior to extraction. Samples were prepared using the automated MicroLab STAR® system from Hamilton Company. Several recovery standards were added prior to the first step in the extraction process for QC purposes. In order to dissociate small molecules bound to or trapped in proteins, lysate was precipitated with methanol under vigorous shaking for 2 min (Glen Mills GenoGrinder 2000) followed by centrifugation. The resulting extract was divided into multiple fractions: two for analysis by two separate reverse phase (RP)/UPLC-MS/MS methods with positive ion mode electrospray ionization (ESI), one for analysis by RP/UPLC-MS/MS with negative ion mode ESI, one for analysis by HILIC/UPLC-MS/MS with negative ion mode ESI, and remaining fractions reserved for backup. Samples were dried under warm nitrogen to remove the organic solvent. The sample extracts were stored sealed at -80C if not analysed immediately |
Processing Storage Conditions: | -80℃ |
Combined analysis:
Analysis ID | AN005778 | AN005779 | AN005780 | AN005781 |
---|---|---|---|---|
Analysis type | MS | MS | MS | MS |
Chromatography type | Reversed phase | Reversed phase | Reversed phase | HILIC |
Chromatography system | Waters Acquity | Waters Acquity | Waters Acquity | Waters Acquity |
Column | Waters Acquity BEH C18 (100 x 2mm, 1.7um) | Waters Acquity BEH C18 (100 x 2mm, 1.7um) | Waters Acquity BEH C18 (100 x 2mm, 1.7um) | Waters Acquity BEH Amide (150 x 2.1mm, 1.7um) |
MS Type | ESI | ESI | ESI | ESI |
MS instrument type | Orbitrap | Orbitrap | Orbitrap | Orbitrap |
MS instrument name | Thermo Q Exactive Orbitrap | Thermo Q Exactive Orbitrap | Thermo Q Exactive Orbitrap | Thermo Q Exactive Orbitrap |
Ion Mode | POSITIVE | POSITIVE | NEGATIVE | NEGATIVE |
Units | Peak area | Peak area | Peak area | Peak area |
Chromatography:
Chromatography ID: | CH004385 |
Chromatography Summary: | Low pH polar (LC/MS Pos early) |
Instrument Name: | Waters Acquity |
Column Name: | Waters Acquity BEH C18 (100 x 2mm, 1.7um) |
Column Temperature: | 40-50 |
Flow Gradient: | Linear gradient from 5% B to 80% B over 3.35 minutes |
Flow Rate: | 0.35 mL/min |
Solvent A: | 100% water; 0.1% formic acid; 0.05% Pentafluoropropionic Acid, pH ~2.5 |
Solvent B: | 100% methanol; 0.1% formic acid; 0.05% Pentafluoropropionic Acid, pH ~2.5 |
Chromatography Type: | Reversed phase |
Chromatography ID: | CH004386 |
Chromatography Summary: | Low pH Lipophilic (LC/MS Pos late) |
Instrument Name: | Waters Acquity |
Column Name: | Waters Acquity BEH C18 (100 x 2mm, 1.7um) |
Column Temperature: | 40-50 |
Flow Gradient: | Linear gradient from 40% B to 99.5% B over 1.0 minute, hold 99.5% B for 2.4 minutes. |
Flow Rate: | 0.60 mL/min |
Solvent A: | 100% water; 0.1% formic acid; 0.05% Pentafluoropropionic Acid, pH ~2.5 |
Solvent B: | 50% methanol/50% acetonitrile; 0.1% formic acid; 0.05% Pentafluoropropionic Acid, pH ~2.5 |
Chromatography Type: | Reversed phase |
Chromatography ID: | CH004387 |
Chromatography Summary: | High pH (LC/MS Neg) |
Instrument Name: | Waters Acquity |
Column Name: | Waters Acquity BEH C18 (100 x 2mm, 1.7um) |
Column Temperature: | 40-50 |
Flow Gradient: | Linear gradient from 0.5 to 70% B over 4.0 minutes, then rapid gradient to 99% B in 0.5 minutes. |
Flow Rate: | 0.35 mL/min |
Solvent A: | 100% water; 6.5 mM ammonium bicarbonate, pH 8 |
Solvent B: | 95% methanol/5% water; 6.5 mM ammonium bicarbonate |
Chromatography Type: | Reversed phase |
Chromatography ID: | CH004388 |
Chromatography Summary: | HILIC (LC/MS Polar Neg) |
Instrument Name: | Waters Acquity |
Column Name: | Waters Acquity BEH Amide (150 x 2.1mm, 1.7um) |
Column Temperature: | 40-50 |
Flow Gradient: | Linear gradient from 5% B to 50% B in 3.5 minutes, then linear gradient from 50% B to 95% B in 2 minutes. |
Flow Rate: | 0.50 mL/min |
Solvent A: | 15% water/5% methanol/80% acetonitrile; 10 mM ammonium formate, (effective pH 10.16 with ammonium hydroxide) |
Solvent B: | 50% water/50% acetonitrile; 10 mM ammonium formate, (effective pH 10.60 with ammonium hydroxide) |
Chromatography Type: | HILIC |
MS:
MS ID: | MS005498 |
Analysis ID: | AN005778 |
Instrument Name: | Thermo Q Exactive Orbitrap |
Instrument Type: | Orbitrap |
MS Type: | ESI |
MS Comments: | Metabolon (LC/MS Pos early) - MS/MS was performed on a Thermo Scientific Q-Exactive high resolution/accurate mass spectrometer interfaced with a heated electrospray ionization (HESI-II) source and Orbitrap mass analyzer operated at 35,000 mass resolution. The MS analysis alternated between MS and data-dependent MSn scans using dynamic exclusion. The scan range varied slighted between methods but covered 70-1000 m/z. Note: In our dataset, cells marked as 'blank (i.e. empty cells)' indicate that the metabolite was either not present in the sample or the measurement fell below the detection limits of our instruments. Essentially, we didn't find any trace of the metabolite, or it was too low to measure accurately. On the other hand, cells labeled 'ND' (which stands for "Not Detected") occur when we consolidate data from different experiments. If a metabolite wasn’t detected in one or more of the individual experiments but was present in others, we mark it as 'ND' in the consolidated dataset. This label helps us understand that while the metabolite was identified in some datasets, it was absent in others, possibly due to variations in experimental conditions or sample differences. By using these distinct labels, we ensure that anyone analyzing the data can clearly understand whether a metabolite was consistently undetectable across all experiments ('blank') or if it was found in some but not all ('ND'). This clarity helps in analyzing the data accurately, avoiding confusion between experimental absence and measurement limitations. |
Ion Mode: | POSITIVE |
MS ID: | MS005499 |
Analysis ID: | AN005779 |
Instrument Name: | Thermo Q Exactive Orbitrap |
Instrument Type: | Orbitrap |
MS Type: | ESI |
MS Comments: | Metabolon (LC/MS Pos late) - MS/MS was performed on a Thermo Scientific Q-Exactive high resolution/accurate mass spectrometer interfaced with a heated electrospray ionization (HESI-II) source and Orbitrap mass analyzer operated at 35,000 mass resolution. The MS analysis alternated between MS and data-dependent MSn scans using dynamic exclusion. The scan range varied slighted between methods but covered 70-1000 m/z. Note: In our dataset, cells marked as 'blank (i.e. empty cells)' indicate that the metabolite was either not present in the sample or the measurement fell below the detection limits of our instruments. Essentially, we didn't find any trace of the metabolite, or it was too low to measure accurately. On the other hand, cells labeled 'ND' (which stands for "Not Detected") occur when we consolidate data from different experiments. If a metabolite wasn’t detected in one or more of the individual experiments but was present in others, we mark it as 'ND' in the consolidated dataset. This label helps us understand that while the metabolite was identified in some datasets, it was absent in others, possibly due to variations in experimental conditions or sample differences. By using these distinct labels, we ensure that anyone analyzing the data can clearly understand whether a metabolite was consistently undetectable across all experiments ('blank') or if it was found in some but not all ('ND'). This clarity helps in analyzing the data accurately, avoiding confusion between experimental absence and measurement limitations. |
Ion Mode: | POSITIVE |
MS ID: | MS005500 |
Analysis ID: | AN005780 |
Instrument Name: | Thermo Q Exactive Orbitrap |
Instrument Type: | Orbitrap |
MS Type: | ESI |
MS Comments: | Metabolon (LC/MS Neg) - MS/MS was performed on a Thermo Scientific Q-Exactive high resolution/accurate mass spectrometer interfaced with a heated electrospray ionization (HESI-II) source and Orbitrap mass analyzer operated at 35,000 mass resolution. The MS analysis alternated between MS and data-dependent MSn scans using dynamic exclusion. The scan range varied slighted between methods but covered 70-1000 m/z. Note: In our dataset, cells marked as 'blank (i.e. empty cells)' indicate that the metabolite was either not present in the sample or the measurement fell below the detection limits of our instruments. Essentially, we didn't find any trace of the metabolite, or it was too low to measure accurately. On the other hand, cells labeled 'ND' (which stands for "Not Detected") occur when we consolidate data from different experiments. If a metabolite wasn’t detected in one or more of the individual experiments but was present in others, we mark it as 'ND' in the consolidated dataset. This label helps us understand that while the metabolite was identified in some datasets, it was absent in others, possibly due to variations in experimental conditions or sample differences. By using these distinct labels, we ensure that anyone analyzing the data can clearly understand whether a metabolite was consistently undetectable across all experiments ('blank') or if it was found in some but not all ('ND'). This clarity helps in analyzing the data accurately, avoiding confusion between experimental absence and measurement limitations. |
Ion Mode: | NEGATIVE |
MS ID: | MS005501 |
Analysis ID: | AN005781 |
Instrument Name: | Thermo Q Exactive Orbitrap |
Instrument Type: | Orbitrap |
MS Type: | ESI |
MS Comments: | Metabolon (LC/MS Polar) - MS/MS was performed on a Thermo Scientific Q-Exactive high resolution/accurate mass spectrometer interfaced with a heated electrospray ionization (HESI-II) source and Orbitrap mass analyzer operated at 35,000 mass resolution. The MS analysis alternated between MS and data-dependent MSn scans using dynamic exclusion. The scan range varied slighted between methods but covered 70-1000 m/z. Note: In our dataset, cells marked as 'blank (i.e. empty cells)' indicate that the metabolite was either not present in the sample or the measurement fell below the detection limits of our instruments. Essentially, we didn't find any trace of the metabolite, or it was too low to measure accurately. On the other hand, cells labeled 'ND' (which stands for "Not Detected") occur when we consolidate data from different experiments. If a metabolite wasn’t detected in one or more of the individual experiments but was present in others, we mark it as 'ND' in the consolidated dataset. This label helps us understand that while the metabolite was identified in some datasets, it was absent in others, possibly due to variations in experimental conditions or sample differences. By using these distinct labels, we ensure that anyone analyzing the data can clearly understand whether a metabolite was consistently undetectable across all experiments ('blank') or if it was found in some but not all ('ND'). This clarity helps in analyzing the data accurately, avoiding confusion between experimental absence and measurement limitations. |
Ion Mode: | NEGATIVE |