The ABRF Metabolomics Research Group 2013 Study: Investigation of Spiked Compound Differences in a Human Plasma Matrix.
Metabolomics is an emerging field that involves qualitative and quantitative measurements of small molecule metabolites in a biological system. These measurements can be useful for developing biomarkers for diagnosis, prognosis, or predicting response to therapy. Currently, a wide variety of metabolomics approaches, including nontargeted and targeted profiling, are used across laboratories on a routine basis. A diverse set of analytical platforms, such as NMR, gas chromatography-mass spectrometry, Orbitrap mass spectrometry, and time-of-flight-mass spectrometry, which use various chromatographic and ionization techniques, are used for resolution, detection, identification, and quantitation of metabolites from various biological matrices. However, few attempts have been made to standardize experimental methodologies or comparative analyses across different laboratories. The Metabolomics Research Group of the Association of Biomolecular Resource Facilities organized a "round-robin" experiment type of interlaboratory study, wherein human plasma samples were spiked with different amounts of metabolite standards in 2 groups of biologic samples (A and B). The goal was a study that resembles a typical metabolomics analysis. Here, we report our efforts and discuss challenges that create bottlenecks for the field. Finally, we discuss benchmarks that could be used by laboratories to compare their methodologies.
1 Department of Oncology and 2 Department of Biochemistry, Molecular and Cellular Biology, and 3 Department of Biostatistics, Bioinformatics and Biomathematics, Georgetown University Medical Center, Washington, DC, USA; 4 Division of Signal Transduction, Beth Israel Deaconess Medical Center, and Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA; 5 Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, New York, USA; 6 Berg, New York, New York, USA; and 7 Max Planck Institute of Psychiatry, Munich, Germany.
Amrita K
AK
Cheema
1 Department of Oncology and 2 Department of Biochemistry, Molecular and Cellular Biology, and 3 Department of Biostatistics, Bioinformatics and Biomathematics, Georgetown University Medical Center, Washington, DC, USA; 4 Division of Signal Transduction, Beth Israel Deaconess Medical Center, and Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA; 5 Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, New York, USA; 6 Berg, New York, New York, USA; and 7 Max Planck Institute of Psychiatry, Munich, Germany.
John M
JM
Asara
1 Department of Oncology and 2 Department of Biochemistry, Molecular and Cellular Biology, and 3 Department of Biostatistics, Bioinformatics and Biomathematics, Georgetown University Medical Center, Washington, DC, USA; 4 Division of Signal Transduction, Beth Israel Deaconess Medical Center, and Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA; 5 Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, New York, USA; 6 Berg, New York, New York, USA; and 7 Max Planck Institute of Psychiatry, Munich, Germany.
Yiwen
Y
Wang
1 Department of Oncology and 2 Department of Biochemistry, Molecular and Cellular Biology, and 3 Department of Biostatistics, Bioinformatics and Biomathematics, Georgetown University Medical Center, Washington, DC, USA; 4 Division of Signal Transduction, Beth Israel Deaconess Medical Center, and Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA; 5 Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, New York, USA; 6 Berg, New York, New York, USA; and 7 Max Planck Institute of Psychiatry, Munich, Germany.
Thomas A
TA
Neubert
1 Department of Oncology and 2 Department of Biochemistry, Molecular and Cellular Biology, and 3 Department of Biostatistics, Bioinformatics and Biomathematics, Georgetown University Medical Center, Washington, DC, USA; 4 Division of Signal Transduction, Beth Israel Deaconess Medical Center, and Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA; 5 Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, New York, USA; 6 Berg, New York, New York, USA; and 7 Max Planck Institute of Psychiatry, Munich, Germany.
Vladimir
V
Tolstikov
1 Department of Oncology and 2 Department of Biochemistry, Molecular and Cellular Biology, and 3 Department of Biostatistics, Bioinformatics and Biomathematics, Georgetown University Medical Center, Washington, DC, USA; 4 Division of Signal Transduction, Beth Israel Deaconess Medical Center, and Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA; 5 Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, New York, USA; 6 Berg, New York, New York, USA; and 7 Max Planck Institute of Psychiatry, Munich, Germany.
Chris W
CW
Turck
D015415:Biomarkers / Q000097:blood; D002853:Chromatography, Liquid; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000592:standards; D013058:Mass Spectrometry / Q000592:standards; D055442:Metabolome; D055432:Metabolomics / Q000592:standards*; D012015:Reference Standards
D015415:Biomarkers
NMR; mass spectrometry; targeted metabolomics; untargeted metabolomics