Detectability of Plasma Proteins in SRM Measurements

Author(s): Olga I. Kiseleva* , Elena A. Ponomarenko , Yulia A. Romashova , Ekaterina V. Poverennaya , Andrey V. Lisitsa .

Journal Name: Current Proteomics

Volume 16 , Issue 1 , 2019

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Abstract:

Background: Liquid chromatography coupled with targeted mass spectrometry underwent rapid technical evolution during last years and has become widely used technology in clinical laboratories. It offers confident specificity and sensitivity superior to those of traditional immunoassays. However, due to controversial reports on reproducibility of SRM measurements, the prospects of clinical appliance of the method are worth discussing.

Objective: The study was aimed at assessment of capabilities of SRM to achieve a thorough assembly of the human plasma proteome.

Method: We examined set of 19 human blood plasma samples to measure 100 proteins, including FDA-approved biomarkers, via SRM-assay.

Results: Out of 100 target proteins 43 proteins were confidently detected in at least two blood plasma sample runs, 36 and 21 proteins were either not detected in any run or inconsistently detected, respectively. Empiric dependences on protein detectability were derived to predict the number of biological samples required to detect with certainty a diagnostically relevant quantum of the human plasma proteome.

Conclusion: The number of samples exponentially increases with an increase in the number of protein targets, while proportionally decreasing to the logarithm of the limit of detection. Analytical sensitivity and enormous proteome heterogeneity are major bottlenecks of the human proteome exploration.

Keywords: Human proteome project, protein detectability, proteomics, SRM, targeted mass spectrometry, blood plasma.

[1]
Archakov, A.; Lisitsa, A.; Ponomarenko, E.; Zgoda, V. Recent advances in proteomic profiling of human blood: Clinical scope. Expert Rev. Proteomics, 2015, 12, 111-113.
[2]
Lange, V.; Picotti, P.; Domon, B.; Aebersold, R. Selected reaction monitoring for quantitative proteomics: A tutorial. Mol. Syst. Biol., 2008, 4, 222.
[3]
Kopylov, A.; Zgoda, V.; Lisitsa, A.; Archakov, A. Combined use of irreversible binding and MRM technology for low- and ultralow copy-number protein detection and quantitation. Proteomics, 2013, 13, 727-742.
[4]
Carr, S.A.; Abbatiello, S.E.; Ackermann, B.L.; Borchers, C.; Domon, B.; Deutsch, E.W.; Grant, R.P.; Hoofnagle, A.N.; Hüttenhain, R.; Koomen, J.M.; Liebler, D.C.; Liu, T.; MacLean, B.; Mani, D.R.; Mansfield, E.; Neubert, H.; Paulovich, A.G.; Reiter, L.; Vitek, O.; Aebersold, R.; Anderson, L.; Bethem, R.; Blonder, J.; Boja, E.; Botelho, J.; Boyne, M.; Bradshaw, R.A.; Burlingame, A.L.; Chan, D.; Keshishian, H.; Kuhn, E.; Kinsinger, C.; Lee, J.S.H.; Lee, S-W.; Moritz, R.; Oses-Prieto, J.; Rifai, N.; Ritchie, J.; Rodriguez, H.; Srinivas, P.R.; Townsend, R.R.; Van Eyk, J.; Whiteley, G.; Wiita, A.; Weintraub, S. Targeted peptide measurements in biology and medicine: Best practices for mass spectrometry-based assay development using a fit-for-purpose approach. Mol. Cell. Proteomics, 2014, 13, 907-917.
[5]
Legrain, P.; Aebersold, R.; Archakov, A.; Bairoch, A.; Bala, K.; Beretta, L.; Bergeron, J.; Borchers, C.H.; Corthals, G.L.; Costello, C.E.; Deutsch, E.W.; Domon, B.; Hancock, W.; He, F.; Hochstrasser, D.; Salekdeh, G.H.; Sechi, S.; Snyder, M.; Srivastava, S.; Uhle, M.; Wu, C.H.; Yamamoto, T.; Paik, Y. The human proteome project: Current state and future direction Mol. Cell. Proteomics,, 2011, 10(7), M111.009993.
[6]
Huttenhain, R.; Soste, M.; Selevsek, N.; Rost, H.; Sethi, A.; Carapito, C.; Farrah, T.; Deutsch, E.W.; Kusebauch, U.; Moritz, R.L.; Nimeus-Malmstrom, E.; Rinner, O.; Aebersold, R. Reproducible quantification of cancer-associated proteins in body fluids using targeted proteomics. Sci. Transl. Med., 2012, 4, 142ra94.
[7]
Archakov, A.; Zgoda, V.; Kopylov, A.; Naryzhny, S.; Chernobrovkin, A.; Ponomarenko, E.; Lisitsa, A. Chromosome-centric approach to overcoming bottlenecks in the human proteome project. Expert Rev. Proteomics, 2012, 9, 667-676.
[8]
Abbatiello, S.E.; Mani, D.R.; Schilling, B.; Maclean, B.; Zimmerman, L.J.; Feng, X.; Cusack, M.P.; Sedransk, N.; Hall, S.C.; Addona, T.; Allen, S.; Dodder, N.G.; Ghosh, M.; Held, J.M.; Hedrick, V.; Inerowicz, H.D.; Jackson, A.; Keshishian, H.; Kim, J.W.; Lyssand, J.S.; Riley, C.P.; Rudnick, P.; Sadowski, P.; Shaddox, K.; Smith, D.; Tomazela, D.; Wahlander, A.; Waldemarson, S.; Whitwell, C.A.; You, J.; Zhang, S.; Kinsinger, C.R.; Mesri, M.; Rodriguez, H.; Borchers, C.H.; Buck, C.; Fisher, S.J.; Gibson, B.W.; Liebler, D.; Maccoss, M.; Neubert, T.A.; Paulovich, A.; Regnier, F.; Skates, S.J.; Tempst, P.; Wang, M.; Carr, S.A. Design, implementation and multisite evaluation of a system suitability protocol for the quantitative assessment of instrument performance in Liquid Chromatography-Multiple Reaction Monitoring-MS (LC-MRM-MS). Mol. Cell. Proteomics, 2013, 12, 2623-2639.
[9]
Addona, T.A.; Abbatiello, S.E.; Schilling, B.; Skates, S.J.; Mani, D.R.; Bunk, D.M.; Spiegelman, C.H.; Zimmerman, L.J.; Ham, A-J.L.; Keshishian, H.; Hall, S.C.; Allen, S.; Blackman, R.K.; Borchers, C.H.; Buck, C.; Cardasis, H.L.; Cusack, M.P.; Dodder, N.G.; Gibson, B.W.; Held, J.M.; Hiltke, T.; Jackson, A.; Johansen, E.B.; Kinsinger, C.R.; Li, J.; Mesri, M.; Neubert, T.A.; Niles, R.K.; Pulsipher, T.C.; Ransohoff, D.; Rodriguez, H.; Rudnick, P.A.; Smith, D.; Tabb, D.L.; Tegeler, T.J.; Variyath, A.M.; Vega-Montoto, L.J.; Wahlander, A.; Waldemarson, S.; Wang, M.; Whiteaker, J.R.; Zhao, L.; Anderson, N.L.; Fisher, S.J.; Liebler, D.C.; Paulovich, A.G.; Regnier, F.E.; Tempst, P.; Carr, S.A. Multi-site assessment of the precision and reproducibility of multiple reaction monitoring-mased measurements of proteins in plasma. Nat. Biotechnol., 2009, 27, 633-641.
[10]
Vialas, V.; Colomé-Calls, N.; Abian, J.; Aloria, K.; Alvarez-Llamas, G.; Antúnez, O.; Arizmendi, J.M.; Azkargorta, M.; Barceló-Batllori, S.; Barderas, M.G.; Blanco, F.; Casal, J.I.; Casas, V.; de la Torre, C.; Chicano-Gálvez, E.; Elortza, F.; Espadas, G.; Estanyol, J.M.; Fernandez-Irigoyen, J.; Fernandez-Puente, P.; Fidalgo, M.J.; Fuentes, M.; Gay, M.; Gil, C.; Hainard, A.; Hernaez, M.L.; Ibarrola, N.; Kopylov, A.T.; Lario, A.; Lopez, J.A.; López-Lucendo, M.; Marcilla, M.; Marina-Ramírez, A.; Marko-Varga, G.; Martín, L.; Mora, M.I.; Morato-López, E.; Muñoz, J.; Odena, M.A.; de Oliveira, E.; Orera, I.; Ortea, I.; Pasquarello, C.; Ray, K.B.; Rezeli, M.; Ruppen, I.; Sabidó, E.; del Pino, M.M.S.; Sancho, J.; Santamaría, E.; Vazquez, J.; Vilaseca, M.; Vivanco, F.; Walters, J.J.; Zgoda, V.G.; Corrales, F.J.; Canals, F.; Paradela, A. A multicentric study to evaluate the use of relative retention times in targeted proteomics. J. Proteomics, 2017, 152, 138-149.
[11]
Percy, A.J.; Tamura-Wells, J.; Albar, J.P.; Aloria, K.; Amirkhani, A.; Araujo, G.D.T.; Arizmendi, J.M.; Blanco, F.J.; Canals, F.; Cho, J-Y.; Colomé-Calls, N.; Corrales, F.J.; Domont, G.; Espadas, G.; Fernandez-Puente, P.; Gil, C.; Haynes, P.A.; Hernáez, M.L.; Kim, J.Y.; Kopylov, A.; Marcilla, M.; McKay, M.J.; Mirzaei, M.; Molloy, M.P.; Ohlund, L.B.; Paik, Y-K.; Paradela, A.; Raftery, M.; Sabidó, E.; Sleno, L.; Wilffert, D.; Wolters, J.C.; Yoo, J.S.; Zgoda, V.; Parker, C.E.; Borchers, C.H. Inter-laboratory evaluation of instrument platforms and experimental workflows for quantitative accuracy and reproducibility assessment. EuPA Open Proteomics., 2015, 8, 6-15.
[12]
Anderson, N.L.; Polanski, M.; Pieper, R.; Gatlin, T.; Tirumalai, R.S.; Conrads, T.P.; Veenstra, T.D.; Adkins, J.N.; Pounds, J.G.; Fagan, R.; Lobley, A. The human plasma proteome: A nonredundant list developed by combination of four separate sources. Mol. Cell. Proteomics, 2004, 3, 311-326.
[13]
Gillet, L.C.; Navarro, P.; Tate, S.; Röst, H.; Selevsek, N.; Reiter, L.; Bonner, R.; Aebersold, R. Targeted data extraction of the MS/MS spectra generated by data-independent acquisition: A new concept for consistent and accurate proteome analysis. Mol. Cell. Proteomics,, 2012, 11, O111.016717.
[14]
Schoenherr, R.M.; Saul, R.G.; Whiteaker, J.R.; Yan, P.; Whiteley, G.R.; Paulovich, A.G. Anti-peptide monoclonal antibodies generated for immuno-multiple reaction monitoring-mass spectrometry assays have a high probability of supporting western blot and ELISA. Mol. Cell. Proeomics, 2015, 14(2), 382-398.
[15]
Kiseleva, O.I.; Romashova, Y.A.; Moskaleva, N.E.; Petushkova, N.A.; Teryaeva, N.B.; Belyaev, A.Y.; Lisitsa, A.V. Plasma preparation to measure FDA-approved protein markers by selected reaction monitoring. Clin. Transl. Med., 2015, 4, 32.
[16]
PlasmaDeepDiveTM MRM assays panel for depleted human plasma-manual, Biognosys AG, Switzerland, 2013, pp. 1-21.
[17]
Escher, C.; Reiter, L.; MacLean, B.; Ossola, R.; Herzog, F.; Chilton, J.; MacCoss, M.J.; Rinner, O. Using iRT, a normalized retention time for more targeted measurement of peptides. Proteomics, 2012, 12, 1111-1121.
[18]
Yadav, A.K.; Bhardwaj, G.; Basak, T.; Kumar, D.; Ahmad, S.; Priyadarshini, R.; Singh, A.K.; Dash, D.; Sengupta, S. A systematic analysis of eluted fraction of plasma post immunoaffinity depletion: Implications in biomarker discovery. PLoS One, 2011, 6, e24442.
[19]
Jones, P.; Côté, R.G.; Martens, L.; Quinn, A.F.; Taylor, C.F.; Derache, W.; Hermjakob, H.; Apweiler, R. PRIDE: A public repository of protein and peptide identifications for the proteomics community. Nucleic Acids Res., 2006, 34, D659-D663.
[20]
Desiere, F.; Deutsch, E.W.; King, N.L.; Nesvizhskii, A.I.; Mallick, P.; Eng, J.; Chen, S.; Eddes, J.; Loevenich, S.N.; Aebersold, R. The peptideatlas project. Nucleic Acids Res., 2006, 34, D655-D658.
[21]
Prakash, A.; Tomazela, D.M.; Frewen, B.; Maclean, B.; Peterman, S.; Maccoss, M.J. Expediting the development of targeted SRM assays: Using data from shotgun proteomics to automate method development. J. Proteome Res., 2010, 8, 2733-2739.
[22]
Farrah, T.; Deutsch, E.W.; Omenn, G.S.; Campbell, D.S.; Sun, Z.; Bletz, J. a; Mallick, P.; Katz, J.E.; Malmström, J.; Ossola, R.; Watts, J.D.; Lin, B.; Zhang, H.; Moritz, R.L.; Aebersold, R. A high-confidence human plasma proteome reference set with estimated concentrations in PeptideAtlas. Mol. Cell. Proteomics, 2011, 10, M110.006353.
[23]
Keshishian, H.; Addona, T.; Burgess, M.; Kuhn, E.; Carr, S.A. Quantitative, multiplexed assays for low abundance proteins in plasma by targeted mass spectrometry and stable isotope dilution. Mol. Cell. Proteomics, 2007, 6, 2212-2229.
[24]
Sapan, C.V.; Lundblad, R.L. Considerations regarding the use of blood samples in the proteomic identification of biomarkers for cancer diagnosis. Cancer Genomics Proteomics, 2006, 3, 227-230.
[25]
Tuck, M.K.; Chan, D.W.; Chia, D.; Godwin, A.K.; Grizzle, W.E.; Krueger, K.E.; Rom, W.; Sanda, M.; Sorbara, L.; Stass, S.; Brenner, D.E. Standard operating procedures for serum and plasma collection: Early detection research network consensus statement standard operating procedure integration working group. J. Proteome Res., 2010, 8, 113-117.
[26]
Wilhelm, M.; Schlegl, J.; Hahne, H.; Moghaddas Gholami, A.; Lieberenz, M.; Savitski, M.M.; Ziegler, E.; Butzmann, L.; Gessulat, S.; Marx, H.; Mathieson, T.; Lemeer, S.; Schnatbaum, K.; Reimer, U.; Wenschuh, H.; Mollenhauer, M.; Slotta-Huspenina, J.; Boese, J-H.; Bantscheff, M.; Gerstmair, A.; Faerber, F.; Kuster, B. Mass-spectrometry-based draft of the human proteome. Nature, 2014, 509, 582-587.
[27]
Kim, M.S.; Pinto, S.M.; Getnet, D.; Nirujogi, R.S.; Manda, S.S.; Chaerkady, R.; Madugundu, A.K.; Kelkar, D.S.; Isserlin, R.; Jain, S.; Thomas, J.K.; Muthusamy, B.; Leal-Rojas, P.; Kumar, P.; Sahasrabuddhe, N.A.; Balakrishnan, L.; Advani, J.; George, B.; Renuse, S.; Selvan, L.D.N.; Patil, A.H.; Nanjappa, V.; Radhakrishnan, A.; Prasad, S.; Subbannayya, T.; Raju, R.; Kumar, M.; Sreenivasamurthy, S.K.; Marimuthu, A.; Sathe, G.J.; Chavan, S.; Datta, K.K.; Subbannayya, Y.; Sahu, A.; Yelamanchi, S.D.; Jayaram, S.; Rajagopalan, P.; Sharma, J.; Murthy, K.R.; Syed, N.; Goel, R.; Khan, A.A.; Ahmad, S.; Dey, G.; Mudgal, K.; Chatterjee, A.; Huang, T-C.; Zhong, J.; Wu, X.; Shaw, P.G.; Freed, D.; Zahari, M.S.; Mukherjee, K.K.; Shankar, S.; Mahadevan, A.; Lam, H.; Mitchell, C.J.; Shankar, S.K.; Satishchandra, P.; Schroeder, J.T.; Sirdeshmukh, R.; Maitra, A.; Leach, S.D.; Drake, C.G.; Halushka, M.K.; Prasad, T.S.K.; Hruban, R.H.; Kerr, C.L.; Bader, G.D.; Iacobuzio-Donahue, C.A.; Gowda, H.; Pandey, A. A draft map of the human proteome. Nature, 2014, 509, 575-581.
[28]
Anderson, N.L.; Anderson, N.G. The human plasma proteome: History, character, and diagnostic prospects. Mol. Cell. Proteomics, 2002, 1, 845-867.
[29]
Thadikkaran, L.; Siegenthaler, M.A.; Crettaz, D.; Queloz, P.; Schneider, P.; Tissot, J. Recent advances in blood-related proteomics. Proteomics, 2005, 5(12), 3019-3034.
[30]
Rose, K.; Bougueleret, L.; Baussant, T.; Böhm, G.; Botti, P.; Colinge, J.; Cusin, I.; Gaertner, H.; Gleizes, A.; Heller, M.; Jimenez, S.; Johnson, A.; Kussmann, M.; Menin, L.; Menzel, C.; Ranno, F.; Rodriguez-Tomé, P.; Rogers, J.; Saudrais, C.; Villain, M.; Wetmore, D.; Bairoch, A.; Hochstrasser, D. Industrial-scale proteomics: From liters of plasma to chemically synthesized proteins. Proteomics, 2004, 4, 2125-2150.
[31]
Petrak, J.; Ivanek, R.; Toman, O.; Cmejla, R.; Cmejlova, J.; Vyoral, D.; Zivny, J.; Vulpe, C.D. Déjà vu in proteomics: A hit parade of repeatedly identified differentially expressed proteins. Proteomics, 2008, 8, 1744-1749.
[32]
Paik, Y-K.; Jeong, S-K.; Omenn, G.S.; Uhlen, M.; Hanash, S.; Cho, S.Y.; Lee, H-J.; Na, K.; Choi, E-Y.; Yan, F.; Zhang, F.; Zhang, Y.; Snyder, M.; Cheng, Y.; Chen, R.; Marko-Varga, G.; Deutsch, E.W.; Kim, H.; Kwon, J-Y.; Aebersold, R.; Bairoch, A.; Taylor, A.D.; Kim, K.Y.; Lee, E-Y.; Hochstrasser, D.; Legrain, P.; Hancock, W.S. The chromosome-centric human proteome project for cataloging proteins encoded in the genome. Nat. Biotechnol., 2012, 30, 221-223.
[33]
Lisitsa, A.; Moshkovskii, S.; Chernobrovkin, A.; Ponomarenko, E.; Archakov, A. Profiling proteoforms: Promising follow-up of proteomics for biomarker discovery. Expert Rev. Proteomics, 2014, 11, 121-129.
[34]
Smith, L.M.; Kelleher, N.L. Proteoform: A single term describing protein complexity. Nat. Methods, 2013, 10, 186-187.


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VOLUME: 16
ISSUE: 1
Year: 2019
Page: [74 - 81]
Pages: 8
DOI: 10.2174/1570164615666180718151135
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