Summary of Study ST002993
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 PR001863. The data can be accessed directly via it's Project DOI: 10.21228/M8WX4S 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 | ST002993 |
| Study Title | Identifying subgroups of childhood obesity by using multiplatform metabotyping |
| Study Summary | Obesity results from an interplay between genetic predisposition and environmental factors such as diet, physical activity, culture, and socioeconomic status. Personalized treatments for obesity would be optimal, thus necessitating the identification of individual characteristics to improve the effectiveness of therapies. For example, genetic impairment of the leptin-melanocortin pathway can result in rare cases of severe early-onset obesity. Metabolomics has the potential to distinguish between a healthy and obese status; however, differentiating subsets of individuals within the obesity spectrum remains challenging. Factor analysis can integrate patient features from diverse sources, allowing an accurate subclassification of individuals. This study presents a workflow to identify metabotypes, particularly when routine clinical studies fail in patient categorization. 110 children with obesity (BMI > +2 SDS) genotyped for nine genes involved in the leptin-melanocortin pathway (CPE, MC3R, MC4R, MRAP2, NCOA1, PCSK1, POMC, SH2B1, and SIM1) and two glutamate receptor genes (GRM7 and GRIK1) were studied; 55 harboring heterozygous rare sequence variants and 55 with no variants. Anthropometric and routine clinical laboratory data were collected, and serum samples processed for untargeted metabolomic analysis using GC-q-MS and CE-TOF-MS and reversed-phase U(H)PLC-QTOF-MS/MS in positive and negative ionization modes. Following signal processing and multialignment, multivariate and univariate statistical analyses were applied to evaluate the genetic trait association with metabolomics data and clinical and routine laboratory features. Neither the presence of a heterozygous rare sequence variant nor clinical/routine laboratory features determined subgroups in the metabolomics data. To identify metabolomic subtypes, we applied Factor Analysis, by constructing a composite matrix from the five analytical platforms. Six factors were discovered and three different metabotypes. Subtle but neat differences in the circulating lipids, as well as in insulin sensitivity could be established, which opens the possibility to personalize the treatment according to the patients categorization into such obesity subtypes. Metabotyping in clinical contexts poses challenges due to the influence of various uncontrolled variables on metabolic phenotypes. However, this strategy reveals the potential to identify subsets of patients with similar clinical diagnoses but different metabolic conditions. This approach underscores the broader applicability of Factor Analysis in metabotyping across diverse clinical scenarios. |
| Institute | Universidad CEU San Pablo |
| Laboratory | CEMBIO |
| Last Name | Chamoso-Sánchez |
| First Name | David |
| Address | Urb. Montepríncipe. 28925 Alcorcón, Madrid (España) |
| david.chamososanchez@usp.ceu.es | |
| Phone | (+34)913724769 |
| Submit Date | 2023-11-07 |
| Num Groups | 2 |
| Total Subjects | 110 |
| Num Males | 53 |
| Num Females | 57 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | mzXML |
| Analysis Type Detail | GC/LC-MS |
| Release Date | 2023-12-04 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Combined analysis:
| Analysis ID | AN004913 | AN004914 | AN004915 | AN004916 | AN004917 |
|---|---|---|---|---|---|
| Analysis type | MS | MS | MS | MS | MS |
| Chromatography type | Reversed phase | Reversed phase | GC | CE | CE |
| Chromatography system | Agilent 1290 Infinity II | Agilent 1290 Infinity II | Agilent 8890 GC System | Agilent 7100 CE | Agilent 7100 CE |
| Column | Agilent InfinityLab Poroshell 120 EC-C18 (100 x 3mm,2.7um) | Agilent InfinityLab Poroshell 120 EC-C18 (100 x 3mm,2.7um) | Agilent DB5-MS (30m x 0.25mm, 0.25um) | Agilent Technologies fused silica capillary (total length, 100 cm; internal diameter, 50 µm) | Agilent Technologies fused polyvinyl alcohol capillary PVA (total length, 97.6 cm; internal diameter, 50 µm) |
| MS Type | ESI | ESI | EI | ESI | EI |
| MS instrument type | QTOF | QTOF | Single quadrupole | TOF | TOF |
| MS instrument name | Agilent 6545 QTOF | Agilent 6545 QTOF | Agilent 5977B | Agilent 6230 TOF | Agilent 6224 TOF |
| Ion Mode | POSITIVE | NEGATIVE | POSITIVE | POSITIVE | NEGATIVE |
| Units | Corrected areas | Corrected areas | Corrected areas | Corrected areas | Corrected areas |
Chromatography:
| Chromatography ID: | CH003708 |
| Chromatography Summary: | UHPLC-QTOF-MS POS |
| Instrument Name: | Agilent 1290 Infinity II |
| Column Name: | Agilent InfinityLab Poroshell 120 EC-C18 (100 x 3mm,2.7um) |
| Column Temperature: | 50 °C |
| Flow Gradient: | Started at 70% of B at 0-1 min, 86% B at 3.5-10 min, 100% B at 11-17 min. The starting conditions were recovered by minute 17. |
| Flow Rate: | 0.6 mL/min |
| Internal Standard: | Sphinganine (D17:0) and palmitic acid-d31 |
| Solvent A: | 90% water/10% methanol; 10 mM ammonium acetate; 0.2 mM ammonium fluoride |
| Solvent B: | 20% acetonitrile/30% methanol/50% isopropanol; 10 mM ammonium acetate; 0.2 mM ammonium fluoride |
| Analytical Time: | 19 min |
| Chromatography Type: | Reversed phase |
| Chromatography ID: | CH003709 |
| Chromatography Summary: | UHPLC-QTOF-MS NEG |
| Instrument Name: | Agilent 1290 Infinity II |
| Column Name: | Agilent InfinityLab Poroshell 120 EC-C18 (100 x 3mm,2.7um) |
| Column Temperature: | 50 °C |
| Flow Gradient: | Started at 70% of B at 0-1 min, 86% B at 3.5-10 min, 100% B at 11-17 min. The starting conditions were recovered by minute 17. |
| Flow Rate: | 0.6 mL/min |
| Internal Standard: | Sphinganine (D17:0) and palmitic acid-d31 |
| Solvent A: | 90% water/10% methanol; 10 mM ammonium acetate; 0.2 mM ammonium fluoride |
| Solvent B: | 20% acetonitrile/30% methanol/50% isopropanol; 10 mM ammonium acetate; 0.2 mM ammonium fluoride |
| Analytical Time: | 19 min |
| Chromatography Type: | Reversed phase |
| Chromatography ID: | CH003710 |
| Chromatography Summary: | GC-MS |
| Instrument Name: | Agilent 8890 GC System |
| Column Name: | Agilent DB5-MS (30m x 0.25mm, 0.25um) |
| Column Temperature: | The temperature of the column was initially set at 60 °C for 1 minute, then raised to 10 °C/min to 325 °C, which was maintained for 10 minutes before cooling |
| Flow Gradient: | Constant |
| Flow Rate: | 0.5508 mL/min |
| Internal Standard: | palmitic acid-d31 and tricosane |
| Solvent A: | Helium |
| Solvent B: | N/A |
| Analytical Time: | 37 min |
| Chromatography Type: | GC |
| Chromatography ID: | CH003711 |
| Chromatography Summary: | CE-MS POS |
| Instrument Name: | Agilent 7100 CE |
| Column Name: | Agilent Technologies fused silica capillary (total length, 100 cm; internal diameter, 50 µm) |
| Column Temperature: | 20 ºC |
| Flow Gradient: | None |
| Flow Rate: | None |
| Internal Standard: | methionine sulfone, paracetamol and 4-morpholineethanesulfonic acid, 2-(N-morpholino)ethanesulfonic acid (MES) |
| Internal Standard Mt: | methionine sulfone |
| Solvent A: | BGE (1 M formic acid solution in 10% methanol (v/v)) |
| Solvent B: | N/A |
| Analytical Time: | 26 min |
| Capillary Voltage: | 30 KV |
| Sheath Liquid: | Methanol: water (1:1, v/v) and two reference masses (20 μL of purine: 121.0509 and 20 μL of HP-0922: 922.0098) at a flow rate of 0.6 mL/min (1:100 of split ratio) |
| Chromatography Type: | CE |
| Chromatography ID: | CH003712 |
| Chromatography Summary: | CE-MS NEG |
| Instrument Name: | Agilent 7100 CE |
| Column Name: | Agilent Technologies fused polyvinyl alcohol capillary PVA (total length, 97.6 cm; internal diameter, 50 µm) |
| Column Temperature: | 20 ºC |
| Flow Gradient: | None |
| Flow Rate: | None |
| Internal Standard: | methionine sulfone, paracetamol and 4-morpholineethanesulfonic acid, 2-(N-morpholino)ethanesulfonic acid (MES) |
| Internal Standard Mt: | methionine sulfone |
| Solvent A: | BGE (0.1 M formic acid solution) |
| Solvent B: | N/A |
| Analytical Time: | 55 min |
| Capillary Voltage: | -30 KV |
| Sheath Liquid: | Methanol: water (1:1, v/v) and two reference masses (20 μL of purine: 121.0509 and 20 μL of HP-0922: 922.0098) at a flow rate of 0.6 mL/min (1:100 of split ratio) |
| Chromatography Type: | CE |
