Summary of Study ST002452

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 PR001581. The data can be accessed directly via it's Project DOI: 10.21228/M8BD85 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.

Perform statistical analysis  |  Show all samples  |  Show named metabolites  |  Download named metabolite data  
Download mwTab file (text)   |  Download mwTab file(JSON)   |  Download data files (Contains raw data)
Study IDST002452
Study TitleLipidomic analysis of human brain from frontotemporal dementia cases of with GRN and C9orf72 mutations
Study SummaryLipidomic analysis carried out on postmortem human brain tissue from cases with FTD carrying inherited mutations in the GRN gene, or repeat expansions in the C9orf72 gene, and age-matched control cases. Tissue was sampled from the heavily affected superior frontal grey and white matter, and less heavily affected superior parietal grey and white matter.
Institute
The University of Sydney
Last NameDon
First NameAnthony
AddressOffice 3217, D17 Charles Perkins Centre, Camperdown, NSW, 2006, Australia
Emailanthony.don@sydney.edu.au
Phone+61286275578
Submit Date2023-01-19
Num Groups3
Total Subjects28
Num Males13
Num Females15
Raw Data AvailableYes
Raw Data File Type(s)mzXML
Analysis Type DetailLC-MS
Release Date2023-03-01
Release Version1
Anthony Don Anthony Don
https://dx.doi.org/10.21228/M8BD85
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:

Project:

Project ID:PR001581
Project DOI:doi: 10.21228/M8BD85
Project Title:Frontotemporal Dementia Human Brain Lipidomics
Project Summary:Frontotemporal dementia (FTD) lipidomic study of human brain from cases with GRN or C9orf72 mutations or controls. We aimed to determine how inherited mutations that cause FTD affect the brain lipidome. Both heterozygous GRN mutations and C9orf72 repeat expansions cause FTD with TDP-43 pathology, but GRN mutation carriers appear to have significant white matter pathology as seen by MRI. Our study uncovered significant loss of myelin sphingolipids in the heavily affected superior frontal white matter in both FTD groups, but GRN carriers show more severe myelin attrition than C9orf72 repeat expansion carriers. GRN carriers also showed selective increase in cholesterol esters and sphingosine in the less affected superior parietal white matter.
Institute:The University of Sydney
Last Name:Don
First Name:Anthony
Address:Office 3217, D17 Charles Perkins Centre, Camperdown, NSW, 2006, Australia
Email:anthony.don@sydney.edu.au
Phone:+61286275578

Subject:

Subject ID:SU002546
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 Genotype Brain region
SA245821918_n_SFG_GMC9orf72 SFG_GM
SA245822806_n_SFG_GMC9orf72 SFG_GM
SA245823732_n_SFG_GMC9orf72 SFG_GM
SA245824806_SFG_GMC9orf72 SFG_GM
SA245825754_SFG_GMC9orf72 SFG_GM
SA245826785_SFG_GMC9orf72 SFG_GM
SA245827785_n_SFG_GMC9orf72 SFG_GM
SA245828754_n_SFG_GMC9orf72 SFG_GM
SA245829625_n_SFG_GMC9orf72 SFG_GM
SA245830729_n_SFG_GMC9orf72 SFG_GM
SA245831526_n_SFG_GMC9orf72 SFG_GM
SA245832448_n_SFG_GMC9orf72 SFG_GM
SA245833736_n_SFG_GMC9orf72 SFG_GM
SA245834436_n_SFG_GMC9orf72 SFG_GM
SA245835736_SFG_GMC9orf72 SFG_GM
SA245836918_SFG_GMC9orf72 SFG_GM
SA245837436_SFG_GMC9orf72 SFG_GM
SA245838732_SFG_GMC9orf72 SFG_GM
SA245839526_SFG_GMC9orf72 SFG_GM
SA245840448_SFG_GMC9orf72 SFG_GM
SA245841729_SFG_GMC9orf72 SFG_GM
SA245842625_SFG_GMC9orf72 SFG_GM
SA245843729_n_SFG_WMC9orf72 SFG_WM
SA245844526_n_SFG_WMC9orf72 SFG_WM
SA245845732_n_SFG_WMC9orf72 SFG_WM
SA245846625_n_SFG_WMC9orf72 SFG_WM
SA245847806_n_SFG_WMC9orf72 SFG_WM
SA245848918_n_SFG_WMC9orf72 SFG_WM
SA245849448_n_SFG_WMC9orf72 SFG_WM
SA245850785_n_SFG_WMC9orf72 SFG_WM
SA245851754_n_SFG_WMC9orf72 SFG_WM
SA245852736_n_SFG_WMC9orf72 SFG_WM
SA245853729_SFG_WMC9orf72 SFG_WM
SA245854785_SFG_WMC9orf72 SFG_WM
SA245855806_SFG_WMC9orf72 SFG_WM
SA245856918_SFG_WMC9orf72 SFG_WM
SA245857436_n_SFG_WMC9orf72 SFG_WM
SA245858754_SFG_WMC9orf72 SFG_WM
SA245859736_SFG_WMC9orf72 SFG_WM
SA245860448_SFG_WMC9orf72 SFG_WM
SA245861526_SFG_WMC9orf72 SFG_WM
SA245862732_SFG_WMC9orf72 SFG_WM
SA245863436_SFG_WMC9orf72 SFG_WM
SA245864625_SFG_WMC9orf72 SFG_WM
SA245865448_SPC_GMC9orf72 SPC_GM
SA245866436_SPC_GMC9orf72 SPC_GM
SA245867526_SPC_GMC9orf72 SPC_GM
SA245868625_SPC_GMC9orf72 SPC_GM
SA245869736_SPC_GMC9orf72 SPC_GM
SA245870729_SPC_GMC9orf72 SPC_GM
SA245871732_n_SPC_GMC9orf72 SPC_GM
SA245872729_n_SPC_GMC9orf72 SPC_GM
SA245873448_n_SPC_GMC9orf72 SPC_GM
SA245874918_n_SPC_GMC9orf72 SPC_GM
SA245875526_n_SPC_GMC9orf72 SPC_GM
SA245876436_n_SPC_GMC9orf72 SPC_GM
SA245877625_n_SPC_GMC9orf72 SPC_GM
SA245878754_SPC_GMC9orf72 SPC_GM
SA245879732_SPC_GMC9orf72 SPC_GM
SA245880785_n_SPC_GMC9orf72 SPC_GM
SA245881806_n_SPC_GMC9orf72 SPC_GM
SA245882785_SPC_GMC9orf72 SPC_GM
SA245883736_n_SPC_GMC9orf72 SPC_GM
SA245884754_n_SPC_GMC9orf72 SPC_GM
SA245885806_SPC_GMC9orf72 SPC_GM
SA245886918_SPC_GMC9orf72 SPC_GM
SA245887736_SPC_WMC9orf72 SPC_WM
SA245888754_SPC_WMC9orf72 SPC_WM
SA245889436_SPC_WMC9orf72 SPC_WM
SA245890732_SPC_WMC9orf72 SPC_WM
SA245891785_SPC_WMC9orf72 SPC_WM
SA245892918_n_SPC_WMC9orf72 SPC_WM
SA245893806_SPC_WMC9orf72 SPC_WM
SA245894729_SPC_WMC9orf72 SPC_WM
SA245895625_SPC_WMC9orf72 SPC_WM
SA245896526_SPC_WMC9orf72 SPC_WM
SA245897448_SPC_WMC9orf72 SPC_WM
SA245898806_n_SPC_WMC9orf72 SPC_WM
SA245899448_n_SPC_WMC9orf72 SPC_WM
SA245900729_n_SPC_WMC9orf72 SPC_WM
SA245901732_n_SPC_WMC9orf72 SPC_WM
SA245902918_SPC_WMC9orf72 SPC_WM
SA245903526_n_SPC_WMC9orf72 SPC_WM
SA245904625_n_SPC_WMC9orf72 SPC_WM
SA245905785_n_SPC_WMC9orf72 SPC_WM
SA245906754_n_SPC_WMC9orf72 SPC_WM
SA245907736_n_SPC_WMC9orf72 SPC_WM
SA245908436_n_SPC_WMC9orf72 SPC_WM
SA245909518_SFG_GMControl SFG_GM
SA245910662_SFG_GMControl SFG_GM
SA245911613_SFG_GMControl SFG_GM
SA245912393_SFG_GMControl SFG_GM
SA245913384_SFG_GMControl SFG_GM
SA245914851_n_SFG_GMControl SFG_GM
SA245915831_n_SFG_GMControl SFG_GM
SA245916758_n_SFG_GMControl SFG_GM
SA245917688_n_SFG_GMControl SFG_GM
SA245918688_SFG_GMControl SFG_GM
SA245919366_SFG_GMControl SFG_GM
SA245920518_n_SFG_GMControl SFG_GM
Showing page 1 of 3     Results:    1  2  3  Next     Showing results 1 to 100 of 224

Collection:

Collection ID:CO002539
Collection Summary:Frozen brain tissue was homogenised by bead beating at 4°C in ice cold HEPES buffer (50mM, pH 7.4) plus 5 mM NaF, 2 mM Na3VO4, 10 mM KCl and cOmplete Mini EDTA-free Protease Inhibitor Cocktail
Sample Type:Brain
Storage Conditions:-80℃

Treatment:

Treatment ID:TR002558
Treatment Summary:Samples were obtained from frontotemporal dementia cases with inherited gene mutations in either GRN, or C9orf72 gene repeat expansion carriers and controls.

Sample Preparation:

Sampleprep ID:SP002552
Sampleprep Summary:Lipids were extracted from 100uL of brain homogenate using a two-phase methyl-tert-butyl ether (MTBE)/methanol/water protocol as described by Matyash et al. (2008), with the addition of the following internal standards: 2000 pmoles SM(d18:1_12:0), 2000 pmoles GluCer(d18:1_12:0), 500 pmoles LacCer(d18:1_12:0), 500 pmoles ST(18:1_17:0), 500 pmoles Cer(18:1/17:0), 200 pmoles C17:0 Sph, 200 pmoles C17:1 S1P, 200 pmoles d3-C16 AcCa, 500 pmoles C17:1 LPE, 500 pmoles C17:1 LPS, 200 pmoles C17:0 LPA, 500 pmoles C17:0 LPC, 5000 pmoles PC(19:0_19:0), 2000 pmoles PS(17:0_17:0), 2000 pmoles C17:0 PE, 2000 pmoles C17:0 PG, 1000 pmoles C17:0 PA, 1000 pmoles d7-18:1_15:0 PI, 2000 pmoles CL(14:0_14:0_14:0_14:0), 2000 pmoles TAG(17:0_17:0_17:0), 500 pmoles DAG d7- 18:1/15:0), 500 pmoles d7- 18:1 MAG, 2000 pmoles C17:0 CholE, 1000 pmoles d7 Chol. Lipids were reconstituted in 400uL of 100% HPLC methanol, then diluted 1/5 in 80% v/v HPLC methanol, containing 1 mM ammonium formate and 0.2% formic acid.

Combined analysis:

Analysis ID AN004007 AN004008
Analysis type MS MS
Chromatography type Reversed phase Reversed phase
Chromatography system Thermo Vanquish Thermo Vanquish
Column Waters ACQUITY UPLC CSH C18 (100 x 2.1mm,1.7um) Waters ACQUITY UPLC CSH C18 (100 x 2.1mm,1.7um)
MS Type ESI ESI
MS instrument type Orbitrap Orbitrap
MS instrument name Thermo Q Exactive HF-X Orbitrap Thermo Q Exactive HF-X Orbitrap
Ion Mode POSITIVE NEGATIVE
Units pmoles/mg protein pmoles/mg protein

Chromatography:

Chromatography ID:CH002959
Instrument Name:Thermo Vanquish
Column Name:Waters ACQUITY UPLC CSH C18 (100 x 2.1mm,1.7um)
Column Temperature:45
Flow Gradient:0 min, 80:20 A/B; 3 min, 80:20 A/B; 5.5 min, 55:45 A/B; 8 min, 36:65 A/B; 13 min, 15:85 A/B; 14 min, 0:100 A/B; 20 min, 0:100 A/B; 20.2 min, 70:30 A/B; 27 min, 70:30 A/B
Flow Rate:0.28 mL/min
Solvent A:60% acetonitrile/40% water; 0.1% formic acid; 10 mM ammonium formate
Solvent B:90% isopropanol/ 10% acetonitrile; 0.1% formic acid; 10 mM ammonium formate
Chromatography Type:Reversed phase

MS:

MS ID:MS003754
Analysis ID:AN004007
Instrument Name:Thermo Q Exactive HF-X Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:MS data was acquired in full scan/data-dependent MS2 (full scan resolution 60,000 FWHM, scan range 220–1600 m/z) in both positive and negative ionization modes. The ten most abundant ions in each cycle were subjected to MS2, with an isolation window of 1.4 m/z, collision energy 30 eV, resolution 17,500 FWHM, maximum integration time 110 ms and dynamic exclusion window 10 s. An exclusion list of background ions was used based on a solvent blank. An inclusion list of the [M+H]+ and [M-H]- ions was used for all internal standards. LipidSearch software v4.2 (Thermo Fisher) was used for lipid annotation, chromatogram alignment, and peak integration from extracted ion chromatograms. Lipid annotation was based on precursor and product ions in both positive and negative ion mode. Individual lipids were expressed as ratios to an internal standard specific for each lipid class, then multiplied by the amount of internal standard added to produce a molar amount of each lipid per sample, which was normalised to protein amount in each sample.
Ion Mode:POSITIVE
  
MS ID:MS003755
Analysis ID:AN004008
Instrument Name:Thermo Q Exactive HF-X Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:MS data was acquired in full scan/data-dependent MS2 (full scan resolution 60,000 FWHM, scan range 220–1600 m/z) in both positive and negative ionization modes. The ten most abundant ions in each cycle were subjected to MS2, with an isolation window of 1.4 m/z, collision energy 30 eV, resolution 17,500 FWHM, maximum integration time 110 ms and dynamic exclusion window 10 s. An exclusion list of background ions was used based on a solvent blank. An inclusion list of the [M+H]+ and [M-H]- ions was used for all internal standards. LipidSearch software v4.2 (Thermo Fisher) was used for lipid annotation, chromatogram alignment, and peak integration from extracted ion chromatograms. Lipid annotation was based on precursor and product ions in both positive and negative ion mode. Individual lipids were expressed as ratios to an internal standard specific for each lipid class, then multiplied by the amount of internal standard added to produce a molar amount of each lipid per sample, which was normalised to protein amount in each sample.
Ion Mode:NEGATIVE
  logo