Summary of Study ST003303
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 PR002053. The data can be accessed directly via it's Project DOI: 10.21228/M87N78 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 | ST003303 |
| Study Title | Metabolic Alterations in Aneurysmal Subarachnoid Hemorrhage |
| Study Summary | Aneurysmal subarachnoid hemorrhage (aSAH) is a severe type of stroke that is associated with poor outcome. A subset of patients with aSAH will develop secondary complications, most notably delayed cerebral ischemia (DCI), which potentiates neurological injury. In this study, we investigate the relationship between cerebrospinal fluid (CSF) iron accumulation, brain metabolism, and neuronal injury in aSAH patients with or without DCI. We collected longitudinal CSF samples of patients immediately after hospitalization and 5-8 days after onset of ictus. CSF was analyzed with metabolomics to determine metabolic alterations associated with aSAH and DCI. Metabolomic profiling of the CSF samples uncovered significant dysregulation of metabolic pathways associated with energy generation and amino acid utilization, consistent with mitochondrial dysfunction. Using machine learning, we identified a set of metabolites that predicted ICU length of stay (LOS). aSAH alters the CSF metabolome involved in mitochondrial function and a subset of these metabolites are predictive of ICU stay. These results identify potential biomarkers for mitochondrial pathology and provide insight into alterations in brain iron metabolism triggered by aSAH. |
| Institute | University of Akron |
| Department | Chemistry |
| Last Name | Pacheco |
| First Name | Gardenia |
| Address | 190 E. Buchtel Common, Akron, OH 44325 |
| gardenia.pacheco2@gmail.com | |
| Phone | 815-299-2731 |
| Submit Date | 2024-07-02 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | mzML |
| Analysis Type Detail | LC-MS |
| Release Date | 2024-07-29 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Project:
| Project ID: | PR002053 |
| Project DOI: | doi: 10.21228/M87N78 |
| Project Title: | Metabolic Alterations in Aneurysmal Subarachnoid Hemorrhage |
| Project Summary: | Aneurysmal subarachnoid hemorrhage (aSAH) is a severe type of stroke that is associated with poor outcome. A subset of patients with aSAH will develop secondary complications, most notably delayed cerebral ischemia (DCI), which potentiates neurological injury. In this study, we investigate the relationship between cerebrospinal fluid (CSF) iron accumulation, brain metabolism, and neuronal injury in aSAH patients with or without DCI. We collected longitudinal CSF samples of patients immediately after hospitalization and 5-8 days after onset of ictus. CSF was analyzed with metabolomics to determine metabolic alterations associated with aSAH and DCI. Metabolomic profiling of the CSF samples uncovered significant dysregulation of metabolic pathways associated with energy generation and amino acid utilization, consistent with mitochondrial dysfunction. Using machine learning, we identified a set of metabolites that predicted ICU length of stay (LOS). aSAH alters the CSF metabolome involved in mitochondrial function and a subset of these metabolites are predictive of ICU stay. These results identify potential biomarkers for mitochondrial pathology and provide insight into alterations in brain iron metabolism triggered by aSAH. |
| Institute: | University of Akron |
| Department: | Chemistry |
| Last Name: | Pacheco |
| First Name: | Gardenia |
| Address: | 190 E. Buchtel Common, Akron, OH 44325 |
| Email: | gardenia.pacheco2@gmail.com |
| Phone: | 815-299-2731 |
Subject:
| Subject ID: | SU003424 |
| Subject Type: | Human |
| Subject Species: | Homo sapiens |
| Taxonomy ID: | 9606 |
| Species Group: | Mammals |
Factors:
Subject type: Human; Subject species: Homo sapiens (Factor headings shown in green)
| mb_sample_id | local_sample_id | Sample_Group |
|---|---|---|
| SA358546 | 10C | Control |
| SA358547 | 3C | Control |
| SA358548 | 12C | Control |
| SA358549 | 11C | Control |
| SA358550 | 1C | Control |
| SA358551 | 9C | Control |
| SA358552 | 6C | Control |
| SA358553 | 5C | Control |
| SA358554 | 7C | Control |
| SA358555 | 4C | Control |
| SA358556 | 14P1 | SAH_Early |
| SA358557 | 20P1 | SAH_Early |
| SA358558 | 19P1 | SAH_Early |
| SA358559 | 15P1 | SAH_Early |
| SA358560 | 17P1 | SAH_Early |
| SA358561 | 13P1 | SAH_Early |
| SA358562 | 12P1 | SAH_Early |
| SA358563 | 11P1 | SAH_Early |
| SA358564 | 7P1 | SAH_Early |
| SA358565 | 6P1 | SAH_Early |
| SA358566 | 5P1 | SAH_Early |
| SA358567 | 12P2 | SAH_Late |
| SA358568 | 20P2 | SAH_Late |
| SA358569 | 19P2 | SAH_Late |
| SA358570 | 18P2 | SAH_Late |
| SA358571 | 17P2 | SAH_Late |
| SA358572 | 16P2 | SAH_Late |
| SA358573 | 15P2 | SAH_Late |
| SA358574 | 14P2 | SAH_Late |
| SA358575 | 13P2 | SAH_Late |
| SA358576 | 4P2 | SAH_Late |
| SA358577 | 11P2 | SAH_Late |
| SA358578 | 10P2 | SAH_Late |
| SA358579 | 9P2 | SAH_Late |
| SA358580 | 8P2 | SAH_Late |
| SA358581 | 7P2 | SAH_Late |
| SA358582 | 6P2 | SAH_Late |
| SA358583 | 5P2 | SAH_Late |
| SA358584 | 3P2 | SAH_Late |
| SA358585 | 2P2 | SAH_Late |
| SA358586 | 1P2 | SAH_Late |
| Showing results 1 to 41 of 41 |
Collection:
| Collection ID: | CO003417 |
| Collection Summary: | Samples of cerebrospinal fluid (CSF) were obtained from the EVD within the first 24 hours (early sample), and once between days 5 and 8 (late sample) following the onset of ictus. Fluid was obtained from the burette attached to the EVD system, allowing only sampling of fresh CSF. A total of 6 mL were collected at each time point and immediately centrifuged at 2,000 g for 10 minutes in the Cleveland Clinic Genetics core laboratory. The (non-cellular) supernatant was aliquoted in small polypropylene cryovials and stored in liquid nitrogen to avoid auto-oxidation of samples (9). The time elapsed from sample collection to storage in liquid nitrogen was kept under 30 minutes. Control CSF was obtained from patients with suspected neurological disease and seen at the “lumbar puncture clinic” that resulted normal after testing analysis and imaging studies. This study was conducted in accordance with all local IRB guidelines, and informed consent was obtained from all individual participants or their next of kin/legally authorized representatives. Additional CSF samples from aSAH patients and controls were obtained as diagnostic remnants from Accio Biobank Online. |
| Sample Type: | Cerebrospinal fluid |
| Volumeoramount Collected: | 6 mL |
| Storage Conditions: | Described in summary |
| Storage Vials: | Polypropylene cryovials |
Treatment:
| Treatment ID: | TR003433 |
| Treatment Summary: | Samples of cerebrospinal fluid (CSF) were obtained from the EVD within the first 24 hours (early sample), and once between days 5 and 8 (late sample) following the onset of ictus. |
Sample Preparation:
| Sampleprep ID: | SP003431 |
| Sampleprep Summary: | Small molecules were extracted from patient CSF samples using a modified method prior to metabolomic analysis (11). A 100 μL CSF aliquot was selected and thawed on ice for all patients analyzed. Each sample was transferred to a 1.5 mL microcentrifuge tube. For protein precipitation, 400 μL of cold methanol (4X sample volume) was added to each sample, vortexed, and incubated at -20°C for 2 h. Following this incubation period, samples were centrifuged at 13,200 rpm for 20 min at 4°C. The supernatant was transferred to a new 1.5 mL microcentrifuge tube and then dried down in a CentriVap Concentrator (LABCONCO, Kansas, MO, USA). The dry samples were maintained at -80°C until analysis was performed. |
| Extract Storage: | -80℃ |
Chromatography:
| Chromatography ID: | CH004104 |
| Chromatography Summary: | Ultra-high performance LC (UHPLC)/MS was performed with an Agilent 1290 Infinity II LC System interfaced with an Agilent QTOF 6545 Mass Spectrometer. Hydrophilic interaction liquid chromatography (HILIC) was conducted with a HILICON iHILIC-(P) Classic HILIC column (100 mm x 2.1 mm, 5 µm). Mobile-phase solvents were composed of A = 20 mM ammonium bicarbonate, 0.1 % ammonium hydroxide and 2.5 µM medronic acid in water:acetonitrile (95:5) and B = 2.5 µM medronic acid in acetonitrile:water (95:5). The column compartment was maintained at 45 ºC for all experiments. The following linear gradient was applied at a flow rate of 250 µL min-1: 0-1 min: 90 % B, 1-12 min: 90-35 % B, 12-12.5 min: 35-25 % B, 12.5-14.5 min: 25 % B. The column was re-equilibrated with 20 column volumes of 90% B. The injection volume was 4 µL for all samples. |
| Instrument Name: | Agilent 1290 Infinity II |
| Column Name: | HILICON iHILIC-(P) Classic HILIC column (100 x 2.1 mm, 5 µm) |
| Column Temperature: | 45 |
| Flow Gradient: | 0-1 min: 90 % B, 1-12 min: 90-35 % B, 12-12.5 min: 35-25 % B, 12.5-14.5 min: 25 % B |
| Flow Rate: | 250 µL min |
| Sample Injection: | 4 µL |
| Solvent A: | 95% Water, 5% Acetonitrile; 20 mM ammonium bicarbonate; 0.1% ammonium hydroxide; 2.5 µM medronic acid |
| Solvent B: | 95% Acetonitrile, 5% Water; 2.5 µM medronic acid |
| Capillary Voltage: | -3 kV |
| Chromatography Type: | HILIC |
Analysis:
| Analysis ID: | AN005413 |
| Analysis Type: | MS |
| Chromatography ID: | CH004104 |
| Has Mz: | 1 |
| Has Rt: | 1 |
| Rt Units: | Minutes |
| Results File: | ST003303_AN005413_Results.txt |
| Units: | Peak area |