Targeted Quantitative Screening of Chromosome 18 Encoded Proteome in Plasma Samples of Astronaut Candidates.

This work was aimed at estimating the concentrations of proteins encoded by human chromosome 18 (Chr 18) in plasma samples of 54 healthy male volunteers (aged 20-47). These young persons have been certified by the medical evaluation board as healthy subjects ready for space flight training. Over 260 stable isotope-labeled peptide standards (SIS) were synthesized to perform the measurements of proteins encoded by Chr 18. Selected reaction monitoring (SRM) with SIS allowed an estimate of the levels of 84 of 276 proteins encoded by Chr 18. These proteins were quantified in whole and depleted plasma samples. Concentration of the proteins detected varied from 10-6 M (transthyretin, P02766) to 10-11 M (P4-ATPase, O43861). A minor part of the proteins (mostly representing intracellular proteins) was characterized by extremely high inter individual variations. The results provide a background for studies of a potential biomarker in plasma among proteins encoded by Chr 18. The SRM raw data are available in ProteomeXchange repository (PXD004374).

[1]  E. Bertini,et al.  Recessive mutations in EPG5 cause Vici syndrome, a multisystem disorder with defective autophagy , 2012, Nature Genetics.

[2]  P. Mathers,et al.  Mutations in the human RAX homeobox gene in a patient with anophthalmia and sclerocornea. , 2003, Human molecular genetics.

[3]  A. Brivanlou,et al.  APCDD1 is a novel Wnt inhibitor mutated in hereditary hypotrichosis simplex , 2010, Nature.

[4]  D. Fekkes.  State-of-the-art of high-performance liquid chromatographic analysis of amino acids in physiological samples. , 1996, Journal of chromatography. B, Biomedical applications.

[5]  M. Farrer,et al.  Genetic variation of the mitochondrial complex I subunit NDUFV2 and Parkinson's disease. , 2010, Parkinsonism & related disorders.

[6]  A. G. Kessel,et al.  Molecular mechanisms underlying human synovial sarcoma development. , 2001 .

[7]  A. Lang,et al.  Mutations in GNAL cause primary torsion dystonia , 2012, Nature Genetics.

[8]  Alexander V. Tyakht,et al.  Chromosome 18 transcriptoproteome of liver tissue and HepG2 cells and targeted proteome mapping in depleted plasma: update 2013. , 2014, Journal of proteome research.

[9]  P. Plevani,et al.  Mutations in the mitochondrial protease gene AFG3L2 cause dominant hereditary ataxia SCA28 , 2010, Nature Genetics.

[10]  Eugene A. Kapp,et al.  Overview of the HUPO Plasma Proteome Project: Results from the pilot phase with 35 collaborating laboratories and multiple analytical groups, generating a core dataset of 3020 proteins and a publicly‐available database , 2005, Proteomics.

[11]  Leigh Anderson,et al.  Quantitative Mass Spectrometric Multiple Reaction Monitoring Assays for Major Plasma Proteins* , 2006, Molecular & Cellular Proteomics.

[12]  K. Page,et al.  Fast conventional Fmoc solid‐phase peptide synthesis with HCTU , 2008, Journal of peptide science : an official publication of the European Peptide Society.

[13]  N Leigh Anderson,et al.  High-abundance polypeptides of the human plasma proteome comprising the top 4 logs of polypeptide abundance. , 2008, Clinical chemistry.

[14]  Ashutosh Kumar Singh,et al.  A Systematic Analysis of Eluted Fraction of Plasma Post Immunoaffinity Depletion: Implications in Biomarker Discovery , 2011, PloS one.

[15]  B. Cormand,et al.  Implication of Chromosome 18 in Hypertension by Sibling Pair and Association Analyses: Putative Involvement of the RKHD2 Gene , 2006, Hypertension.

[16]  M. Skinner,et al.  Characterization of transthyretin variants in familial transthyretin amyloidosis by mass spectrometric peptide mapping and DNA sequence analysis. , 2002, Analytical chemistry.

[17]  Mehdi Mirzaei,et al.  Inter-laboratory evaluation of instrument platforms and experimental workflows for quantitative accuracy and reproducibility assessment , 2015 .

[18]  E. Bellei,et al.  High-abundance proteins depletion for serum proteomic analysis: concomitant removal of non-targeted proteins , 2010, Amino Acids.

[19]  J. Lupski,et al.  De novo truncating mutations in ASXL3 are associated with a novel clinical phenotype with similarities to Bohring-Opitz syndrome , 2013, Genome Medicine.

[20]  Ruedi Aebersold,et al.  Quantitative variability of 342 plasma proteins in a human twin population , 2015 .

[21]  Xiao-jun Li,et al.  An integrated quantification method to increase the precision, robustness, and resolution of protein measurement in human plasma samples , 2015, Clinical Proteomics.

[22]  Anthony Sandler,et al.  Whole-Exome Sequencing Identifies Homozygous AFG3L2 Mutations in a Spastic Ataxia-Neuropathy Syndrome Linked to Mitochondrial m-AAA Proteases , 2011, PLoS genetics.

[23]  J. Uitto,et al.  Herlitz junctional epidermolysis bullosa: novel and recurrent mutations in the LAMB3 gene and the population carrier frequency. , 2000, The Journal of investigative dermatology.

[24]  Susan E. Abbatiello,et al.  Targeted Peptide Measurements in Biology and Medicine: Best Practices for Mass Spectrometry-based Assay Development Using a Fit-for-Purpose Approach* , 2014, Molecular & Cellular Proteomics.

[25]  R. Kaufman,et al.  ERGIC-53 gene structure and mutation analysis in 19 combined factors V and VIII deficiency families. , 1999, Blood.

[26]  S. Leal,et al.  Homozygous mutations in LPIN2 are responsible for the syndrome of chronic recurrent multifocal osteomyelitis and congenital dyserythropoietic anaemia (Majeed syndrome) , 2005, Journal of Medical Genetics.

[27]  M. Mann,et al.  Universal sample preparation method for proteome analysis , 2009, Nature Methods.

[28]  S. Nanko,et al.  Association of mitochondrial complex I subunit gene NDUFV2 at 18p11 with bipolar disorder , 2003, American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics.

[29]  Jonathan E. Moore,et al.  An unusual N-terminal deletion of the laminin alpha3a isoform leads to the chronic granulation tissue disorder laryngo-onycho-cutaneous syndrome. , 2003, Human molecular genetics.

[30]  J. Haddow,et al.  A point mutation in transthyretin increases affinity for thyroxine and produces euthyroid hyperthyroxinemia. , 1990, The Journal of clinical investigation.

[31]  A. Tolun,et al.  Truncating mutations in TAF4B and ZMYND15 causing recessive azoospermia , 2014, Journal of Medical Genetics.

[32]  E. Zackai,et al.  Mutations in TGIF cause holoprosencephaly and link NODAL signalling to human neural axis determination , 2000, Nature Genetics.

[33]  J. Inazawa,et al.  Novel targets for the 18p11.3 amplification frequently observed in esophageal squamous cell carcinomas. , 2002, Carcinogenesis.

[34]  S. Hanash,et al.  Challenges in deriving high-confidence protein identifications from data gathered by a HUPO plasma proteome collaborative study , 2006, Nature Biotechnology.

[35]  G. Rechavi,et al.  Multiple congenital anomalies-hypotonia-seizures syndrome is caused by a mutation in PIGN , 2011, Journal of Medical Genetics.

[36]  S. Tanase,et al.  Familial carpal tunnel syndrome due to amyloidogenic transthyretin His 114 variant , 1994, Neurology.

[37]  Christoph H Borchers,et al.  Standardized protocols for quality control of MRM-based plasma proteomic workflows. , 2013, Journal of proteome research.

[38]  K. Kohda,et al.  Association of mitochondrial complex I subunit gene NDUFV2 at 18p11 with schizophrenia in the Japanese population , 2006, American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics.

[39]  Adrian J. Ecker,et al.  Mars 520-d mission simulation reveals protracted crew hypokinesis and alterations of sleep duration and timing , 2013, Proceedings of the National Academy of Sciences.

[40]  D. Busam,et al.  SMAD2, SMAD3 and SMAD4 mutations in colorectal cancer. , 2013, Cancer research.

[41]  Oliver Sieber,et al.  A genome-wide association study shows that common alleles of SMAD7 influence colorectal cancer risk , 2007, Nature Genetics.

[42]  Brendan MacLean,et al.  Bioinformatics Applications Note Gene Expression Skyline: an Open Source Document Editor for Creating and Analyzing Targeted Proteomics Experiments , 2022 .

[43]  J. Shendure,et al.  Mutations in KCTD1 cause scalp-ear-nipple syndrome. , 2013, American journal of human genetics.

[44]  Carlos Torroja,et al.  Mutations in the NOTCH pathway regulator MIB1 cause left ventricular noncompaction cardiomyopathy , 2013, Nature Medicine.

[45]  A. Lisitsa,et al.  Recent advances in proteomic profiling of human blood: clinical scope , 2015, Espert Review of Proteomics.

[46]  Christoph H Borchers,et al.  Enhanced sensitivity and multiplexing with 2D LC/MRM-MS and labeled standards for deeper and more comprehensive protein quantitation. , 2014, Journal of proteomics.

[47]  Hye-Won Shin,et al.  ATP9B, a P4-ATPase (a Putative Aminophospholipid Translocase), Localizes to the trans-Golgi Network in a CDC50 Protein-independent Manner* , 2011, The Journal of Biological Chemistry.