Summary of Study ST001637

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 PR001047. The data can be accessed directly via it's Project DOI: 10.21228/M8C68D 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.

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Study IDST001637
Study TitleA Metabolome Atlas of the Aging Mouse Brain
Study SummaryThe mammalian brain relies on neurochemistry to fulfill its functions. Yet, the complexity of the brain metabolome and its changes during diseases or aging remains poorly understood. To start bridging this gap, we generated a metabolome atlas of the aging mouse brain from 10 anatomical regions spanning from adolescence to late adulthood. We combined data from three chromatography-based mass spectrometry assays and structurally annotated 1,709 metabolites to reveal the underlying architecture of aging-induced changes in the brain metabolome. Overall differences between sexes were minimal. We found 94% of all metabolites to significantly differ between brain sections in at least one age group. We also discovered that 90% of the metabolome showed significant changes with respect to age groups. For example, we identified a shift in sphingolipid patterns during aging that is related to myelin remodeling in the transition from adolescent to adult brains. This shift was accompanied by large changes in overall signature in a range of other metabolic pathways. We found clear metabolic similarities in brain sections that were functionally related such as brain stem, cerebrum and cerebellum. In cerebrum, metabolic correlation patterns got markedly weaker in the transition from adolescent to ear adults, whereas correlation patterns between cerebrum and brainstem regions decreased from early to late adulthood. We were also able to map metabolic changes to gene and protein brain atlases to link molecular changes to metabolic brain phenotypes. Metabolic profiles can be investigated via https://atlas.metabolomics.us/. This new resource enables brain researchers to link new metabolomic studies to a foundation data set.
Institute
University of California, Davis
DepartmentGenome Center
LaboratoryWest Coast Metabolomics Center
Last NameDing
First NameJun
Address451 East Health Science Drive, Davis, CA, 95616, USA
Emailjunding@ucdavis.edu
Phone773-326-5420
Submit Date2020-12-23
Raw Data AvailableYes
Raw Data File Type(s)raw(Thermo)
Analysis Type DetailGC-MS/LC-MS
Release Date2021-08-30
Release Version1
Jun Ding Jun Ding
https://dx.doi.org/10.21228/M8C68D
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Combined analysis:

Analysis ID AN002675 AN002676 AN002677 AN002678 AN002679
Analysis type MS MS MS MS MS
Chromatography type HILIC HILIC Reversed phase Reversed phase GC
Chromatography system Thermo Vanquish Thermo Vanquish Thermo Vanquish Thermo Vanquish Agilent 6890N
Column Waters XBridge Amide (100 x 4.6mm,3.5um) Waters XBridge Amide (100 x 4.6mm,3.5um) Waters Acquity CSH C18 (100 x 2.1mm,1.7um) Waters Acquity CSH C18 (100 x 2.1mm,1.7um) Restek Rtx-5Sil (30m x 0.25mm,0.25um)
MS Type ESI ESI ESI ESI EI
MS instrument type Orbitrap LTQ-FT Orbitrap Ion trap GC-TOF
MS instrument name Thermo Q Exactive HF hybrid Orbitrap Thermo Q Exactive HF hybrid Orbitrap Thermo Q Exactive HF hybrid Orbitrap Thermo Q Exactive HF hybrid Orbitrap Leco Pegasus IV TOF
Ion Mode POSITIVE NEGATIVE POSITIVE NEGATIVE POSITIVE
Units Peak height Peak height Peak height Peak height Peak height

MS:

MS ID:MS002474
Analysis ID:AN002675
Instrument Name:Thermo Q Exactive HF hybrid Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:The ion source conditions were set as follows: spray voltage, 3.6 kV; sheath gas flow rate, 60 arbitrary units; aux gas flow rate, 25 arbitrary units; sweep gas flow rate, 2 arbitrary units; capillary temp, 300 °C; S-lens RF level, 50; Aux gas heater temp, 370 °C. The following acquisition parameters were used for MS1 analysis: resolution, 60000, AGC target, 1e6; Maximum IT, 100 ms; scan range 60-900 m/z; spectrum data type, centroid. Data dependent MS/MS parameters: resolution, 15000; AGC target, 1e5; maximum IT, 50 ms; loop count, 4; TopN, 4; isolation window, 1.0 m/z; fixed first mass, 70.0 m/z; (N)CE/ stepped nce, 20, 30, 40; spectrum data type, centroid; minimum AGC target, 8e3; intensity threshold, 1.6e5; exclude isotopes, on; dynamic exclusion, 3.0 s. To increase the total number of MS/MS spectra, five runs with iterative MS/MS exclusions were performed using the R package “IE-Omics”18 for both positive and negative electrospray conditions. All the LC-MS raw data files were converted into ABF format using ABF converter (https://www.reifycs.com/AbfConverter/). MS-DIAL ver.4.00 software was used for deconvolution, peak picking, alignment, and compound identification19. The detailed parameter setting was as follows: MS1 tolerance, 0.005 Da; MS2 tolerance, 0.01 Da; minimum peak height, 20000 amplitude; mass slice width, 0.1 Da; smoothing method, linear weighted moving average; smoothing level, 5 scans; minimum peak width, 10 scans. [M+H]+, [M+NH4]+, [M+Na]+, [2M+H]+,[2M+NH4]+, [2M+Na]+ were included in adduct ion setting for positive mode lipidomics and HILIC analysis, [M-H]-, [M+Cl]-, [M+Hac-H]- for negative mode lipidomics, and [M-H]-, [M+Cl]-, [M+FA-H]-, [2M-H]- for negative mode HILIC analysis. Compounds were annotated by matching retention times, accurate precursor masses and MS/MS spectra against libraries in MassBank of North America and NIST17. Retention time libraries were produced from authentic standards and extrapolated for lipids as published before. The primary result data matrix was processed with MS-FLO software to identify ion adducts, duplicate peaks, and isotopic features. Systematic error removal by random forest (SERRF software) was employed to correct for batch effects or instrument signal drifts. Statistical analysis was performed by normalization to the median intensity of all identified compounds, log transformation and Pareto scaling. PCA was used for multivariate statistics and visualization, specifically for outlier detection. Two outliers, including one medulla sample from a female early adult and one basal ganglia sample from a female late adult, were removed. Results from Kruskal-Wallis tests were followed by Dunn’s multiple comparison confinement. Results from Mann–Whitney U tests were corrected by the Benjamini–Hochberg procedure to control the false discovery rate. Spearman rank correlation analyses and fold change calculations were conducted using R.
Ion Mode:POSITIVE
  
MS ID:MS002475
Analysis ID:AN002676
Instrument Name:Thermo Q Exactive HF hybrid Orbitrap
Instrument Type:LTQ-FT
MS Type:ESI
MS Comments:The ion source conditions were set as follows: spray voltage, -3.0 kV; sheath gas flow rate, 60 arbitrary units; aux gas flow rate, 25 arbitrary units; sweep gas flow rate, 2 arbitrary units; capillary temp, 300 °C; S-lens RF level, 50; Aux gas heater temp, 370 °C. The following acquisition parameters were used for MS1 analysis: resolution, 60000, AGC target, 1e6; Maximum IT, 100 ms; scan range 60-900 m/z; spectrum data type, centroid. Data dependent MS/MS parameters: resolution, 15000; AGC target, 1e5; maximum IT, 50 ms; loop count, 4; TopN, 4; isolation window, 1.0 m/z; fixed first mass, 70.0 m/z; (N)CE/ stepped nce, 20, 30, 40; spectrum data type, centroid; minimum AGC target, 8e3; intensity threshold, 1.6e5; exclude isotopes, on; dynamic exclusion, 3.0 s. To increase the total number of MS/MS spectra, five runs with iterative MS/MS exclusions were performed using the R package “IE-Omics”18 for both positive and negative electrospray conditions. All the LC-MS raw data files were converted into ABF format using ABF converter (https://www.reifycs.com/AbfConverter/). MS-DIAL ver.4.00 software was used for deconvolution, peak picking, alignment, and compound identification19. The detailed parameter setting was as follows: MS1 tolerance, 0.005 Da; MS2 tolerance, 0.01 Da; minimum peak height, 20000 amplitude; mass slice width, 0.1 Da; smoothing method, linear weighted moving average; smoothing level, 5 scans; minimum peak width, 10 scans. [M+H]+, [M+NH4]+, [M+Na]+, [2M+H]+,[2M+NH4]+, [2M+Na]+ were included in adduct ion setting for positive mode lipidomics and HILIC analysis, [M-H]-, [M+Cl]-, [M+Hac-H]- for negative mode lipidomics, and [M-H]-, [M+Cl]-, [M+FA-H]-, [2M-H]- for negative mode HILIC analysis. Compounds were annotated by matching retention times, accurate precursor masses and MS/MS spectra against libraries in MassBank of North America and NIST17. Retention time libraries were produced from authentic standards and extrapolated for lipids as published before. The primary result data matrix was processed with MS-FLO software to identify ion adducts, duplicate peaks, and isotopic features. Systematic error removal by random forest (SERRF software) was employed to correct for batch effects or instrument signal drifts. Statistical analysis was performed by normalization to the median intensity of all identified compounds, log transformation and Pareto scaling. PCA was used for multivariate statistics and visualization, specifically for outlier detection. Two outliers, including one medulla sample from a female early adult and one basal ganglia sample from a female late adult, were removed. Results from Kruskal-Wallis tests were followed by Dunn’s multiple comparison confinement. Results from Mann–Whitney U tests were corrected by the Benjamini–Hochberg procedure to control the false discovery rate. Spearman rank correlation analyses and fold change calculations were conducted using R.
Ion Mode:NEGATIVE
  
MS ID:MS002476
Analysis ID:AN002677
Instrument Name:Thermo Q Exactive HF hybrid Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:The ion source conditions were set as follows: spray voltage, 3.6 kV; sheath gas flow rate, 60 arbitrary units; aux gas flow rate, 25 arbitrary units; sweep gas flow rate, 2 arbitrary units; capillary temp, 300 °C; S-lens RF level, 50; Aux gas heater temp, 370 °C. The following acquisition parameters were used for MS1 analysis: resolution, 60000, AGC target, 1e6; Maximum IT, 100 ms; scan range 150-1700 m/z; spectrum data type, centroid. Data dependent MS/MS parameters: resolution, 15000; AGC target, 1e5; maximum IT, 50 ms; loop count, 4; TopN, 4; isolation window, 1.0 m/z; fixed first mass, 70.0 m/z; (N)CE/ stepped nce, 20, 30, 40; spectrum data type, centroid; minimum AGC target, 8e3; intensity threshold, 1.6e5; exclude isotopes, on; dynamic exclusion, 3.0 s. To increase the total number of MS/MS spectra, five runs with iterative MS/MS exclusions were performed using the R package “IE-Omics”18 for both positive and negative electrospray conditions. All the LC-MS raw data files were converted into ABF format using ABF converter (https://www.reifycs.com/AbfConverter/). MS-DIAL ver.4.00 software was used for deconvolution, peak picking, alignment, and compound identification19. The detailed parameter setting was as follows: MS1 tolerance, 0.005 Da; MS2 tolerance, 0.01 Da; minimum peak height, 20000 amplitude; mass slice width, 0.1 Da; smoothing method, linear weighted moving average; smoothing level, 5 scans; minimum peak width, 10 scans. [M+H]+, [M+NH4]+, [M+Na]+, [2M+H]+,[2M+NH4]+, [2M+Na]+ were included in adduct ion setting for positive mode lipidomics and HILIC analysis, [M-H]-, [M+Cl]-, [M+Hac-H]- for negative mode lipidomics, and [M-H]-, [M+Cl]-, [M+FA-H]-, [2M-H]- for negative mode HILIC analysis. Compounds were annotated by matching retention times, accurate precursor masses and MS/MS spectra against libraries in MassBank of North America and NIST17. Retention time libraries were produced from authentic standards and extrapolated for lipids as published before. The primary result data matrix was processed with MS-FLO software to identify ion adducts, duplicate peaks, and isotopic features. Systematic error removal by random forest (SERRF software) was employed to correct for batch effects or instrument signal drifts. Statistical analysis was performed by normalization to the median intensity of all identified compounds, log transformation and Pareto scaling. PCA was used for multivariate statistics and visualization, specifically for outlier detection. Two outliers, including one medulla sample from a female early adult and one basal ganglia sample from a female late adult, were removed. Results from Kruskal-Wallis tests were followed by Dunn’s multiple comparison confinement. Results from Mann–Whitney U tests were corrected by the Benjamini–Hochberg procedure to control the false discovery rate. Spearman rank correlation analyses and fold change calculations were conducted using R.
Ion Mode:POSITIVE
  
MS ID:MS002477
Analysis ID:AN002678
Instrument Name:Thermo Q Exactive HF hybrid Orbitrap
Instrument Type:Ion trap
MS Type:ESI
MS Comments:The ion source conditions were set as follows: spray voltage, -3.0 kV; sheath gas flow rate, 60 arbitrary units; aux gas flow rate, 25 arbitrary units; sweep gas flow rate, 2 arbitrary units; capillary temp, 300 °C; S-lens RF level, 50; Aux gas heater temp, 370 °C. The following acquisition parameters were used for MS1 analysis: resolution, 60000, AGC target, 1e6; Maximum IT, 100 ms; scan range 150-1700 m/z; spectrum data type, centroid. Data dependent MS/MS parameters: resolution, 15000; AGC target, 1e5; maximum IT, 50 ms; loop count, 4; TopN, 4; isolation window, 1.0 m/z; fixed first mass, 70.0 m/z; (N)CE/ stepped nce, 20, 30, 40; spectrum data type, centroid; minimum AGC target, 8e3; intensity threshold, 1.6e5; exclude isotopes, on; dynamic exclusion, 3.0 s. To increase the total number of MS/MS spectra, five runs with iterative MS/MS exclusions were performed using the R package “IE-Omics”18 for both positive and negative electrospray conditions. All the LC-MS raw data files were converted into ABF format using ABF converter (https://www.reifycs.com/AbfConverter/). MS-DIAL ver.4.00 software was used for deconvolution, peak picking, alignment, and compound identification19. The detailed parameter setting was as follows: MS1 tolerance, 0.005 Da; MS2 tolerance, 0.01 Da; minimum peak height, 20000 amplitude; mass slice width, 0.1 Da; smoothing method, linear weighted moving average; smoothing level, 5 scans; minimum peak width, 10 scans. [M+H]+, [M+NH4]+, [M+Na]+, [2M+H]+,[2M+NH4]+, [2M+Na]+ were included in adduct ion setting for positive mode lipidomics and HILIC analysis, [M-H]-, [M+Cl]-, [M+Hac-H]- for negative mode lipidomics, and [M-H]-, [M+Cl]-, [M+FA-H]-, [2M-H]- for negative mode HILIC analysis. Compounds were annotated by matching retention times, accurate precursor masses and MS/MS spectra against libraries in MassBank of North America and NIST17. Retention time libraries were produced from authentic standards and extrapolated for lipids as published before. The primary result data matrix was processed with MS-FLO software to identify ion adducts, duplicate peaks, and isotopic features. Systematic error removal by random forest (SERRF software) was employed to correct for batch effects or instrument signal drifts. Statistical analysis was performed by normalization to the median intensity of all identified compounds, log transformation and Pareto scaling. PCA was used for multivariate statistics and visualization, specifically for outlier detection. Two outliers, including one medulla sample from a female early adult and one basal ganglia sample from a female late adult, were removed. Results from Kruskal-Wallis tests were followed by Dunn’s multiple comparison confinement. Results from Mann–Whitney U tests were corrected by the Benjamini–Hochberg procedure to control the false discovery rate. Spearman rank correlation analyses and fold change calculations were conducted using R.
Ion Mode:NEGATIVE
  
MS ID:MS002478
Analysis ID:AN002679
Instrument Name:Leco Pegasus IV TOF
Instrument Type:GC-TOF
MS Type:EI
MS Comments:0.5 μL sample was injected with 25 s splitless time on an Agilent 6890 GC (Agilent Technologies, Santa Clara, CA) using a Restek Rtx-5Sil MS column (30 m x 0.25 mm, 0.25 μm) with 10 m Guard column (10 m x 0.25 mm, 0.25 μm) and 1 mL/min Helium gas flow. Oven temperature was held 50°C for 1 min, ramped up to 330 °C at 20 °C/min and held for 5 min. Data was acquired at 70 eV electron ionization at 17 spectra/s from 85 to 500 Da at 1850 V detector voltage on a Leco Pegasus IV time-of-flight mass spectrometer (Leco Corporation, St. Joseph, MI). The transfer line temperature was held at 280 °C with an ion source temperature set at 250 °C. Standard metabolites mixtures and blank samples were injected at the beginning of the run and every ten samples throughout the run for quality control. Raw data was preprocessed by ChromaTOF version 4.50 for baseline subtraction, deconvolution and peak detection. Binbase was used for metabolite annotation and reporting.
Ion Mode:POSITIVE
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