SysQuan: Repurposing SILAC Mice for the Cost-Effective Absolute Quantitation of the Human Proteome
Molecular & Cellular Proteomics, vol. 24, pp. 100974
Abstract
Relative quantitation, used by most mass spectrometry-based proteomics laboratories to determine protein fold-changes, requires samples being processed and analyzed together for best comparability through minimizing batch differences. This limits the adoption of mass spectrometry-based proteomics in population-wide studies and the detection of subtle but relevant changes in heterogeneous samples. Absolute quantitation circumvents these limitations and enables comparison of results across laboratories, studies, and over time. However, high cost of the essential stable isotope labeled (SIL) standards prevents widespread access and limits the number of quantifiable proteins. Our new approach, called "SysQuan", repurposes SILAC mouse tissues/biofluids as system-wide internal standards for matched human samples to enable absolute quantitation of, theoretically, two-thirds of the human proteome using 157,086 shared tryptic peptides, of which 73,901 with lysine on the c terminus. We demonstrate that SysQuan enables quantification of 70% and 31% of the liver and plasma proteomes, respectively. We demonstrate for 14 metabolic proteins that abundant SIL mouse tissues enable cost-effective reverse absolute quantitation in, theoretically, 1000s of human samples. Moreover, 10,000s of light/heavy doublets in untargeted SysQuan datasets enable unique postacquisition absolute quantitation. SysQuan empowers researchers to replace relative quantitation with affordable absolute quantitation at scale, making data comparable across laboratories, diseases and tissues, enabling completely novel study designs and increasing reusability of data in repositories.
Authors 10
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Yassene Mohammed Aachen
Leiden University Medical Center · Jewish General Hospital · Lady Davis Institute for Medical Research
Affiliation as printed
Segal Cancer Proteomics Centre, Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada; Gerald Bronfman Department of Oncology, Jewish General Hospital, Montreal, Quebec, Canada; Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The Netherlands
Segal Cancer Proteomics Centre, Jewish General Hospital, Montreal, QC, Canada; Gerald Bronfman Department of Oncology, Jewish General Hospital, Montreal, QC, Canada; Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The Netherlands
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Jewish General Hospital · Lady Davis Institute for Medical Research
Affiliation as printed
Segal Cancer Proteomics Centre, Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada
Segal Cancer Proteomics Centre, Jewish General Hospital, Montreal, QC, Canada
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Affiliation as printed
Manitoba Centre for Proteomics and Systems Biology, University of Manitoba, Winnipeg, Manitoba, Canada
Manitoba Centre for Proteomics and Systems Biology, Winnipeg, MB, Canada
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Affiliation as printed
Manitoba Centre for Proteomics and Systems Biology, University of Manitoba, Winnipeg, Manitoba, Canada
Manitoba Centre for Proteomics and Systems Biology, Winnipeg, MB, Canada
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Affiliation as printed
Manitoba Centre for Proteomics and Systems Biology, University of Manitoba, Winnipeg, Manitoba, Canada
Manitoba Centre for Proteomics and Systems Biology, Winnipeg, MB, Canada
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Affiliation as printed
MRM Proteomics, Inc, Montreal, Quebec, Canada; Faculty of Veterinary Medicine, Department of Clinical Sciences, University of Montreal, Saint-Hyacinthe, Quebec, Canada
MRM Proteomics, Inc, Montreal, QC, Canada; Faculty of Veterinary Medicine, Department of Clinical Sciences, University of Montreal, Saint-Hyacinthe, QC, Canada
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RheinMain University of Applied Sciences
Affiliation as printed
Department of Engineering, Hochschule RheinMain, Rüsselsheim am Main, Germany
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RheinMain University of Applied Sciences
Affiliation as printed
Department of Engineering, Hochschule RheinMain, Rüsselsheim am Main, Germany
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CancerCare Manitoba · University of Manitoba
Affiliation as printed
Manitoba Centre for Proteomics and Systems Biology, University of Manitoba, Winnipeg, Manitoba, Canada; Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada; Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, Manitoba, Canada; Paul Abrechtsen Research Institute, CancerCare Manitoba, Winnipeg, Manitoba, Canada. Electronic address: Rene.Zahedi@umanitoba.ca
Manitoba Centre for Proteomics and Systems Biology, Winnipeg, MB, Canada; Department of Internal Medicine, University of Manitoba, Winnipeg, MB, Canada; Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, MB, Canada; Paul Abrechtsen Research Institute, CancerCare Manitoba, Winnipeg, MB, Canada. Electronic address: Rene.Zahedi@umanitoba.ca
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Jewish General Hospital · Lady Davis Institute for Medical Research · McGill University
Affiliation as printed
Segal Cancer Proteomics Centre, Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada; Gerald Bronfman Department of Oncology, Jewish General Hospital, Montreal, Quebec, Canada; Division of Experimental Medicine, McGill University, Montreal, Quebec, Canada; Department of Pathology, McGill University, Montreal, Quebec, Canada. Electronic address: Christoph.borchers@mcgill.ca
Segal Cancer Proteomics Centre, Jewish General Hospital, Montreal, QC, Canada; Gerald Bronfman Department of Oncology, Jewish General Hospital, Montreal, QC, Canada; Division of Experimental Medicine, McGill University, Montreal, QC, Canada; Department of Pathology, McGill University, Montreal, QC, Canada. Electronic address: Christoph.borchers@mcgill.ca
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