Summary of study ST000412

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 PR000322. The data can be accessed directly via it's Project DOI: 10.21228/M8V312 This work is supported by NIH grant, U2C- DK119886.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

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Study IDST000412
Study TitleMetabolic profiling during ex vivo machine perfusion of the human liver (part I)
Study SummaryAs donor organ shortages persist, functional machine perfusion is under investigation to improve preservation of the donor liver. The transplantation of donation after circulatory death (DCD) livers is limited by poor outcomes, but its application may be expanded by ex vivo repair and assessment of the organ before transplantation. Here we employed subnormothermic (21 °C) machine perfusion of discarded human livers combined with metabolomics to gain insight into metabolic recovery during machine perfusion. Improvements in energetic cofactors and redox shifts were observed, as well as reversal of ischemia-induced alterations in selected pathways, including lactate metabolism and increased TCA cycle intermediates. We next evaluated whether DCD livers with steatotic and severe ischemic injury could be discriminated from ‘transplantable’ DCD livers. Metabolomic profiling was able to cluster livers with similar metabolic patterns based on the degree of injury. Moreover, perfusion parameters combined with differences in metabolic factors suggest variable mechanisms that result in poor energy recovery in injured livers. We conclude that machine perfusion combined with metabolomics has significant potential as a clinical instrument for the assessment of preserved livers.
Institute
University of California, Davis
DepartmentGenome and Biomedical Sciences Facility
LaboratoryWCMC Metabolomics Core
Last NameFiehn
First NameOliver
Address1315 Genome and Biomedical Sciences Facility, 451 Health Sciences Drive, Davis, CA 95616
Emailofiehn@ucdavis.edu
Phone(530) 754-8258
Submit Date2016-06-30
Publicationsdoi:10.1038/srep22415
Raw Data AvailableYes
Raw Data File Type(s).peg
Analysis Type DetailGC-MS
Release Date2016-09-23
Release Version1
Oliver Fiehn Oliver Fiehn
https://dx.doi.org/10.21228/M8V312
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Project:

Project ID:PR000322
Project DOI:doi: 10.21228/M8V312
Project Title:Metabolic profiling during ex vivo machine perfusion of the human liver
Project Summary:As donor organ shortages persist, functional machine perfusion is under investigation to improve preservation of the donor liver. The transplantation of donation after circulatory death (DCD) livers is limited by poor outcomes, but its application may be expanded by ex vivo repair and assessment of the organ before transplantation. Here we employed subnormothermic (21 °C) machine perfusion of discarded human livers combined with metabolomics to gain insight into metabolic recovery during machine perfusion. Improvements in energetic cofactors and redox shifts were observed, as well as reversal of ischemia-induced alterations in selected pathways, including lactate metabolism and increased TCA cycle intermediates. We next evaluated whether DCD livers with steatotic and severe ischemic injury could be discriminated from ‘transplantable’ DCD livers. Metabolomic profiling was able to cluster livers with similar metabolic patterns based on the degree of injury. Moreover, perfusion parameters combined with differences in metabolic factors suggest variable mechanisms that result in poor energy recovery in injured livers. We conclude that machine perfusion combined with metabolomics has significant potential as a clinical instrument for the assessment of preserved livers.
Institute:University of California, Davis
Department:Genome and Biomedical Sciences Facility
Laboratory:WCMC Metabolomics Core
Last Name:Fiehn
First Name:Oliver
Address:1315 Genome and Biomedical Sciences Facility, 451 Health Sciences Drive, Davis, CA 95616
Email:ofiehn@ucdavis.edu
Phone:(530) 754-8258
Funding Source:NIH U24DK097154

Subject:

Subject ID:SU000433
Subject Type:Human
Subject Species:Homo sapiens
Taxonomy ID:9606
Species Group:Human

Factors:

Subject type: Human; Subject species: Homo sapiens (Factor headings shown in green)

mb_sample_id local_sample_id Treatment Collection Time
SA020200140404ajlsa44_1fresh liver 1 Hr
SA020201140404ajlsa17_1fresh liver 1 Hr
SA020202140403ajlsa12_1fresh liver 1 Hr
SA020203140404ajlsa15_1fresh liver 2 Hr
SA020204140404ajlsa28_1fresh liver 2 Hr
SA020205140403ajlsa19_1fresh liver 2 Hr
SA020206140403ajlsa30_1fresh liver 3 Hr
SA020207140404ajlsa21_1fresh liver 3 Hr
SA020208140403ajlsa02_1fresh liver 3 Hr
SA020209140404ajlsa02_1nonwarm ischemic liver -
SA020210140404ajlsa06_1nonwarm ischemic liver -
SA020211140404ajlsa04_1nonwarm ischemic liver -
SA020212140403ajlsa34_1nonwarm ischemic liver -
SA020213140403ajlsa13_1nonwarm ischemic liver -
SA020214140404ajlsa07_1nonwarm ischemic liver -
SA020215140403ajlsa15_1nonwarm ischemic liver 1 Hr
SA020216140404ajlsa37_1nonwarm ischemic liver 1 Hr
SA020217140404ajlsa22_1nonwarm ischemic liver 1 Hr
SA020218140404ajlsa01_1nonwarm ischemic liver 1 Hr
SA020219140404ajlsa42_1nonwarm ischemic liver 1 Hr
SA020220140403ajlsa40_1nonwarm ischemic liver 1 Hr
SA020221140403ajlsa37_1nonwarm ischemic liver 2 Hr
SA020222140404ajlsa16_1nonwarm ischemic liver 2 Hr
SA020223140404ajlsa27_1nonwarm ischemic liver 2 Hr
SA020224140404ajlsa36_1nonwarm ischemic liver 2 Hr
SA020225140404ajlsa35_1nonwarm ischemic liver 2 Hr
SA020226140403ajlsa41_1nonwarm ischemic liver 2 Hr
SA020227140403ajlsa03_1nonwarm ischemic liver 3 Hr
SA020228140404ajlsa25_1nonwarm ischemic liver 3 Hr
SA020229140404ajlsa40_1nonwarm ischemic liver 3 Hr
SA020230140404ajlsa34_1nonwarm ischemic liver 3 Hr
SA020231140512actsa18_1nonwarm ischemic liver 3 Hr
SA020232140512actsa07_1nonwarm ischemic liver 3 Hr
SA020233140512actsa17_1nonwarm ischemic liver 3 Hr
SA020234140403ajlsa09_1nonwarm ischemic liver 3 Hr
SA020235140404ajlsa03_1nonwarm ischemic liver 3 Hr
SA020236140404ajlsa10_1steatotic liver -
SA020237140403ajlsa33_1steatotic liver -
SA020238140403ajlsa27_1steatotic liver -
SA020239140404ajlsa19_1steatotic liver -
SA020240140403ajlsa44_1steatotic liver -
SA020241140404ajlsa26_1steatotic liver -
SA020242140404ajlsa23_1steatotic liver 1 Hr
SA020243140403ajlsa01_1steatotic liver 1 Hr
SA020244140404ajlsa33_1steatotic liver 1 Hr
SA020245140404ajlsa14_1steatotic liver 2 Hr
SA020246140403ajlsa16_1steatotic liver 2 Hr
SA020247140403ajlsa31_1steatotic liver 2 Hr
SA020248140403ajlsa08_1steatotic liver 3 Hr
SA020249140404ajlsa20_1steatotic liver 3 Hr
SA020250140403ajlsa50_1steatotic liver 3 Hr
SA020251140404ajlsa12_1warm ischemic liver -
SA020252140404ajlsa32_1warm ischemic liver -
SA020253140404ajlsa09_1warm ischemic liver -
SA020254140512actsa03_1warm ischemic liver -
SA020255140404ajlsa41_1warm ischemic liver -
SA020256140403ajlsa11_1warm ischemic liver -
SA020257140404ajlsa45_1warm ischemic liver -
SA020258140512actsa19_1warm ischemic liver -
SA020259140512actsa01_1warm ischemic liver -
SA020260140403ajlsa47_1warm ischemic liver -
SA020261140404ajlsa05_1warm ischemic liver -
SA020262140403ajlsa35_1warm ischemic liver -
SA020263140403ajlsa45_1warm ischemic liver 1 Hr
SA020264140512actsa13_1warm ischemic liver 1 Hr
SA020265140512actsa06_1warm ischemic liver 1 Hr
SA020266140403ajlsa05_1warm ischemic liver 1 Hr
SA020267140404ajlsa39_1warm ischemic liver 1 Hr
SA020268140403ajlsa49_1warm ischemic liver 1 Hr
SA020269140403ajlsa25_1warm ischemic liver 1 Hr
SA020270140512actsa16_1warm ischemic liver 1 Hr
SA020271140403ajlsa36_1warm ischemic liver 1 Hr
SA020272140403ajlsa04_1warm ischemic liver 1 Hr
SA020273140403ajlsa17_1warm ischemic liver 1 Hr
SA020274140403ajlsa14_1warm ischemic liver 1 Hr
SA020275140403ajlsa21_1warm ischemic liver 2 Hr
SA020276140404ajlsa11_1warm ischemic liver 2 Hr
SA020277140403ajlsa22_1warm ischemic liver 2 Hr
SA020278140404ajlsa29_1warm ischemic liver 2 Hr
SA020279140403ajlsa20_1warm ischemic liver 2 Hr
SA020280140512actsa15_1warm ischemic liver 2 Hr
SA020281140512actsa11_1warm ischemic liver 2 Hr
SA020282140404ajlsa43_1warm ischemic liver 2 Hr
SA020283140404ajlsa24_1warm ischemic liver 2 Hr
SA020284140404ajlsa08_1warm ischemic liver 2 Hr
SA020285140512actsa05_1warm ischemic liver 2 Hr
SA020286140404ajlsa30_1warm ischemic liver 2 Hr
SA020287140512actsa09_1warm ischemic liver 3 Hr
SA020288140512actsa20_1warm ischemic liver 3 Hr
SA020289140512actsa02_1warm ischemic liver 3 Hr
SA020290140403ajlsa18_1warm ischemic liver 3 Hr
SA020291140403ajlsa42_1warm ischemic liver 3 Hr
SA020292140403ajlsa26_1warm ischemic liver 3 Hr
SA020293140403ajlsa06_1warm ischemic liver 3 Hr
SA020294140404ajlsa13_1warm ischemic liver 3 Hr
SA020295140403ajlsa24_1warm ischemic liver 3 Hr
Showing results 1 to 96 of 96

Collection:

Collection ID:CO000427
Collection Summary:Liver biopsies were frozen in liquid nitrogen and then stored at -80. They were then pulverized and the crushed tissue from one biopsy was divided into three 0.6mL tubes, containing ±25-70mg. These are triplicates from each biopsy. Tissue was kept at cryo temperatures throughout.
Collection Protocol Filename:StudyDesign_BoteBruinsma_02.11.14.pdf
Sample Type:Tissue

Treatment:

Treatment ID:TR000447
Treatment Summary:9 livers were run for metabolites at 4 timepoints (0,1,2,3), in triplicate. Warm ischemic livers (27, 8, 34) and non-warm ischemic livers (25, 28, 35) and fresh liver samples (R). Liver 30 was a steatotic liver, for which there were 4 timepoints.
Treatment Protocol Filename:StudyDesign_BoteBruinsma_02.11.14.pdf

Sample Preparation:

Sampleprep ID:SP000440
Sampleprep Summary:1. Weigh 4 mg tissue sample ( muscle 20 mg) in to a 2.0 ml eppendorf tube. Add 1.0 mL extraction solvent to the tissue sample and using GenoGrinder homogenize samples for 45 seconds ensuring that sample resembles a powder. 2. Centrifuge the samples at 2500 rpm. for 5 minutes. Aliquot 2 X 500µl supernatant, one for analysis and one for a backup sample. Store backup aliquot in the -20°C freezer. 3. Evaporate one 500µl aliquot of the sample in the Labconco Centrivap cold trap concentrator to complete dryness 4. The dried aliquot is then re-suspended with 500l 50% acetonitrile (degassed as given) (only for liver and brain samples). 5. Centrifuge for 2 min at 14000 rcf using the centrifuge Eppendorf 5415. 6. Remove supernatant to a new Eppendorff tube. 7. Evaporate the supernatant to dryness in the the Labconco Centrivap cold trap concentrator. 8. Submit to derivatization.
Sampleprep Protocol Filename:SOP_Extraction_of_Liver_Tissue_Samples.pdf

Combined analysis:

Analysis ID AN000652
Analysis type MS
Chromatography type GC
Chromatography system Leco Pegasus III GC
Column Restek Corporation Rtx-5Sil MS
MS Type EI
MS instrument type GC-TOF
MS instrument name Leco Pegasus III GC TOF
Ion Mode POSITIVE
Units counts

Chromatography:

Chromatography ID:CH000470
Methods Filename:Data_Dictionary_Fiehn_laboratory_GCTOF_MS_primary_metabolism_10-15-2013_general.pdf
Instrument Name:Leco Pegasus III GC
Column Name:Restek Corporation Rtx-5Sil MS
Column Pressure:7.7 PSI
Column Temperature:50-330C
Flow Rate:1 ml/min
Injection Temperature:50 C ramped to 250 C by 12 C/s
Sample Injection:0.5 uL
Oven Temperature:50°C for 1 min, then ramped at 20°C/min to 330°C, held constant for 5 min
Transferline Temperature:230C
Washing Buffer:Ethyl Acetate
Sample Loop Size:30 m length x 0.25 mm internal diameter
Randomization Order:Excel generated
Chromatography Type:GC

MS:

MS ID:MS000578
Analysis ID:AN000652
Instrument Name:Leco Pegasus III GC TOF
Instrument Type:GC-TOF
MS Type:EI
Ion Mode:POSITIVE
Ion Source Temperature:250 C
Ionization Energy:70 eV
Mass Accuracy:Nominal
Source Temperature:250 C
Scan Range Moverz:85-500 Da
Scanning Cycle:17 Hz
Scanning Range:85-500 Da
Skimmer Voltage:1850 V
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