Advances in Proteome Analysis by Mass Spectrometry
Year: 2001
Type: article
Abstract: two-dimensional electrophoresis reverse-phase microcapillary liquid chromatography mass spectrometry tandem mass spectrometry electrospray ionization matrix-assisted laser desorption/ionization time-of-flight collision-induced dissociation isotope-coded affinity tag strong cation exchange high performance liquid chromatography The interpretation of the information contained in the genomic sequence of a species with respect to the structure, function, and control of biological processes is a technical and conceptual challenge for current research methods. Systematic and quantitative analysis of gene expression is emerging as a valuable tool to diagnostically distinguish between cell types (1Golub T.R. Slonim D.K. Tamayo P. Huard C. Gaasenbeek M. Mesirov J.P. Coller H. Loh M.L. Downing J.R. Caligiuri M.A. Bloomfield C.D. Lander E.S. Science. 1999; 286: 531-537Crossref PubMed Scopus (9190) Google Scholar, 2Alizadeh A.A. Eisen M.B. Davis R.E. Ma C. Lossos I.S. Rosenwald A. Boldrick J.C. Sabet H. Tran T., Yu, X. Powell J.I. Yang L. Marti G.E. Moore T. Hudson Jr., J. Lu L. Lewis D.B. Tibshirani R. Sherlock G. Chan W.C. Greiner T.C. Weisenburger D.D. Armitage J.O. Warnke R. Staudt L.M. et al.Nature. 2000; 403: 503-511Crossref PubMed Scopus (7996) Google Scholar, 3Scherf U. Ross D.T. Waltham M. Smith L.H. Lee J.K. Tanabe L. Kohn K.W. Reinhold W.C. Myers T.G. Andrews D.T. Scudiero D.A. Eisen M.B. Sausville E.A. Pommier Y. Botstein D. Brown P.O. Weinstein J.N. Nat. Genet. 2000; 24: 236-244Crossref PubMed Scopus (1275) Google Scholar, 4Ross D.T. Scherf U. Eisen M.B. Perou C.M. Rees C. Spellman P. Iyer V. Jeffrey S.S. Van de Rijn M. Waltham M. Pergamenschikov A. Lee J.C. Lashkari D. Shalon D. Myers T.G. Weinstein J.N. Botstein D. Brown P.O. Nat. Genet. 2000; 24: 227-235Crossref PubMed Scopus (1821) Google Scholar, 5Lockhart D.J. Winzeler E.A. Nature. 2000; 405: 827-836Crossref PubMed Scopus (1691) Google Scholar) and to differentiate between states (metabolic, activation, pathological) of a particular cell type (5Lockhart D.J. Winzeler E.A. Nature. 2000; 405: 827-836Crossref PubMed Scopus (1691) Google Scholar, 6Lashkari D.A. DeRisi J.L. McCusker J.H. Namath A.F. Gentile C. Hwang S.Y. Brown P.O. Davis R.W. Proc. Natl. Acad. Sci. U. S. A. 1997; 94: 13057-13062Crossref PubMed Scopus (530) Google Scholar, 7Marton M.J. DeRisi J.L. Bennett H.A. Iyer V.R. Meyer M.R. Roberts C.J. Stoughton R. Burchard J. Slade D. Dai H. Bassett Jr., D.E. Hartwell L.H. Brown P.O. Friend S.H. Nat. Med. 1998; 4: 1293-1301Crossref PubMed Scopus (592) Google Scholar). More elaborate strategies such as the combination of systematic, quantitative gene expression analysis with targeted, hypothesis-guided perturbations of cells are being explored for the comprehensive mechanistic analysis of cellular pathways and processes (5Lockhart D.J. Winzeler E.A. Nature. 2000; 405: 827-836Crossref PubMed Scopus (1691) Google Scholar, 7Marton M.J. DeRisi J.L. Bennett H.A. Iyer V.R. Meyer M.R. Roberts C.J. Stoughton R. Burchard J. Slade D. Dai H. Bassett Jr., D.E. Hartwell L.H. Brown P.O. Friend S.H. Nat. Med. 1998; 4: 1293-1301Crossref PubMed Scopus (592) Google Scholar, 8Holstege F.C. Jennings E.G. Wyrick J.J. Lee T.I. Hengartner C.J. Green M.R. Golub T.R. Lander E.S. Young R.A. Cell. 1998; 95: 717-728Abstract Full Text Full Text PDF PubMed Scopus (1595) Google Scholar, 9Roberts C.J. Nelson B. Marton M.J. Stoughton R. Meyer M.R. Bennett H.A. He Y.D. Dai H. Walker W.L. Hughes T.R. Tyers M. Boone C. Friend S.H. Science. 2000; 287: 873-880Crossref PubMed Scopus (719) Google Scholar, 10Ideker T. Thorsson V. Ranish J.A. Christmas R. Buhler J. Eng J.K. Bumgarner R. Goodlett D.R. Aebersold R. Hood L. Science. 2001; 292: 929-934Crossref PubMed Scopus (1649) Google Scholar). Measuring gene expression at the protein level is potentially more informative than the corresponding measurement at the mRNA level. Proteins, the major catalysts of biological function, contain several dimensions of information that collectively indicate the actual rather than the potential functional state as indicated by mRNA analysis. These include the abundance, state of modification, subcellular location, and three-dimensional structure of proteins and their association with each other and/or with biomolecules of different types. Mass spectrometry has become the analytical technology of choice for many of the aspects of proteome analyses that are reflected by the covalent structure of proteins. This review describes recent, innovative advances in mass spectrometry-based proteome analysis that collectively have converged into a generic new approach to proteomics. The specific advances include high throughput protein identification by multidimensional chromatography, automated tandem mass spectrometry and sequence data base searching, accurate quantification by the application of stable isotope dilution theory to protein analysis, and the targeted isolation of selected analytes by the use of highly selective chemistries. Selected applications of these methods along with speculations about future prospects and directions of proteomics research are also included. The development of methods to separate complex protein mixtures at high resolution by two-dimensional gel electrophoresis (2DE)1 into reproducible patterns (11O'Farrell P.H. J. Biol. Chem. 1975; 250: 4007-4021Abstract Full Text PDF PubMed Google Scholar, 12Klose J. Humangenetik. 1975; 26: 231-243PubMed Google Scholar) presented the opportunity to diagnose quantitative and qualitative differences in the protein composition of two or more cell or tissue samples long before gene array techniques to measure gene expression were conceived. Unfortunately, 2DE by itself was an essentially descriptive technique and, without the availability of reliable tools for the identification of the separated protein species, of limited utility as a molecular biology research tool. This changed in the early 1990s when two revolutionary techniques, matrix-assisted laser desorption ionization (MALDI) time-of-flight (TOF) mass spectrometry (MS) (13Karas M. Hillenkamp F. Anal. Chem. 1988; 60: 2299-2301Crossref PubMed Scopus (4828) Google Scholar, 14Hillenkamp F. Karas M. Beavis R.C. Chait B.T. Anal. Chem. 1991; 63: 1193A-1203ACrossref PubMed Google Scholar) and electrospray ionization (ESI) (15Fenn J.B. Mann M. Meng C.K. Wong S.F. Whitehouse C.M. Science. 1989; 246: 64-71Crossref PubMed Scopus (6314) Google Scholar, 16Banks Jr., J.F. Whitehouse C.M. Methods Enzymol. 1996; 270: 486-519Crossref PubMed Google Scholar) MS and tandem mass spectrometry (MS/MS) replaced the slower and less sensitive chemical degradation methods (17Aebersold R.H. Leavitt J. Saavedra R.A. Hood L.E. Kent S.B. Proc. Natl. Acad. Sci. U. S. A. 1987; 84: 6970-6974Crossref PubMed Scopus (630) Google Scholar, 18Lin C.S. Aebersold R.H. Kent S.B. Varma M. Leavitt J. Mol. Cell. Biol. 1988; 8: 4659-4668Crossref PubMed Scopus (106) Google Scholar) as the methods of choice for the identification of proteins separated by 2DE (19Humphery-Smith I. Cordwell S.J. Blackstock W.P. Electrophoresis. 1997; 18: 1217-1242Crossref PubMed Scopus (229) Google Scholar, 20Dunn M.J. Corbett J.M. Methods Enzymol. 1996; 271: 177-203Crossref PubMed Google Scholar, 21Shevchenko A. Jensen O.N. Podtelejnikov A.V. Sagliocco F. Wilm M. Vorm O. Mortensen P. Boucherie H. Mann M. Proc. Natl. Acad. Sci. U. S. A. 1996; 93: 14440-14445Crossref PubMed Scopus (1298) Google Scholar, 22Clauser K.R. Hall S.C. Smith D.M. Webb J.W. Andrews L.E. Tran H.M. Epstein L.B. Burlingame A.L. Proc. Natl. Acad. Sci. U. S. A. 1995; 92: 5072-5076Crossref PubMed Scopus (201) Google Scholar, 23Pandey A. Mann M. Nature. 2000; 405: 837-846Crossref PubMed Scopus (1942) Google Scholar, 24Patterson S.D. Aebersold R. Electrophoresis. 1995; 16: 1791-1814Crossref PubMed Scopus (368) Google Scholar). Typically, these methods involved excision of gel bands of interest, in-gel digestion of the proteins contained in the band using the enzyme trypsin (25Shevchenko A. Wilm M. Vorm O. Mann M. Anal. Chem. 1996; 68: 850-858Crossref PubMed Scopus (7806) Google Scholar), and finally mass spectrometric analysis of the peptides produced. Protein identification was accomplished using peptide-mass fingerprinting by MALDI-TOF MS, as initially described by Henzelet al. (26Henzel W.J. Billeci T.M. Stults J.T. Wong S.C. Grimley C. Watanabe C. Proc. Natl. Acad. Sci. U. S. A. 1993; 90: 5011-5015Crossref PubMed Scopus (1181) Google Scholar) and independently by others (reviewed in Ref.23Pandey A. Mann M. Nature. 2000; 405: 837-846Crossref PubMed Scopus (1942) Google Scholar), nano-ESI tandem mass spectrometry (MS/MS) (27Wilm M. Shevchenko A. Houthaeve T. Breit S. Schweigerer L. Fotsis T. Mann M. Nature. 1996; 379: 466-469Crossref PubMed Scopus (1507) Google Scholar, 28Wilm M. Mann M. Anal. Chem. 1996; 68: 1-8Crossref PubMed Scopus (1703) Google Scholar), or reverse-phase (RP) microcapillary liquid chromatography (μLC) ESI MS/MS (29Shabanowitz J. Settlage R.E. Marto J.A. Christian R.E. White F.M. Russo P.S. Martin S.E. Hunt D.F. Burlingame A.L. Carr S.A. Baldwin M.A. Mass Spectrometry in Biology and Medicine. Humana Press, Totowa, NJ2000: 163-177Google Scholar, 30Hunt D.F. Henderson R.A. Shabanowitz J. Sakaguchi K. Michel H. Sevilir N. Cox A.L. Appella E. Engelhard V.H. Science. 1992; 255: 1261-1263Crossref PubMed Scopus (1049) Google Scholar, 31McCormack A.L. Schieltz D.M. Goode B. Yang S. Barnes G. Drubin D. Yates III, J.R. Anal. Chem. 1997; 69: 767-776Crossref PubMed Scopus (446) Google Scholar, 32Davis M.T. Stahl D.C. Hefta S.A. Lee T.D. Anal. Chem. 1995; 67: 4549-4556Crossref PubMed Scopus (201) Google Scholar, 33Ducret A. Van Oostveen I. Eng J.K. Yates III, J.R. Aebersold R. Protein Sci. 1998; 7: 706-719Crossref PubMed Scopus (280) Google Scholar, 34Haynes P.A. Fripp N. Aebersold R. Electrophoresis. 1998; 19: 939-945Crossref PubMed Scopus (62) Google Scholar) using automated, data-dependent scanning and dynamic exclusion of peptide ions already analyzed in the same experiment (29Shabanowitz J. Settlage R.E. Marto J.A. Christian R.E. White F.M. Russo P.S. Martin S.E. Hunt D.F. Burlingame A.L. Carr S.A. Baldwin M.A. Mass Spectrometry in Biology and Medicine. Humana Press, Totowa, NJ2000: 163-177Google Scholar, 35Gatlin C.L. Eng J.K. Cross S.T. Detter J.C. Yates III, J.R. Anal. Chem. 2000; 72: 757-763Crossref PubMed Scopus (215) Google Scholar, 36Figeys D. Aebersold R. Electrophoresis. 1997; 18: 360-368Crossref PubMed Scopus (72) Google Scholar, 37Courchesne P.L. Jones M.D. Robinson J.H. Spahr C.S. McCracken S. Bentley D.L. Luethy R. Patterson S.D. Electrophoresis. 1998; 19: 956-967Crossref PubMed Scopus (39) Google Scholar). The tandem mass spectra produced by the collision-induced dissociation (CID) (38Hunt D.F. Yates III, J.R. Shabanowitz J. Winston S. Hauer C.R. Proc. Natl. Acad. Sci. U. S. A. 1986; 83: 6233-6237Crossref PubMed Scopus (1074) Google Scholar, 39Papayannopoupos I.A. Mass Spectrom. Rev. 1995; 14: 49-73Crossref Scopus (587) Google Scholar) of selected peptides are searched against theoretical tandem mass spectra of peptide sequences contained in a data base using a variety of search algorithms (40Beavis R.C. Fenyo D. Mann M. Blackstock W. Proteomics: a Trends Guide. Elsevier, London2000: 22-27Google Scholar), the pioneering program being Sequest developed by Eng et al.(41Eng J. McCormack A.L. Yates III, J.R. J. Am. Soc. Mass Spectrom. 1994; 5: 976-989Crossref PubMed Scopus (5419) Google Scholar). The specific techniques and instruments have been reviewed in detail and are not discussed further here (42Blackstock W. Mann M. Blackstock W. Proteomics: a Trends Guide. Elsevier, London2000: 12-17Google Scholar, 43Yates III, J.R. Trends Genet. 2000; 16: 5-8Abstract Full Text Full Text PDF PubMed Scopus (325) Google Scholar). It has become apparent that the 2DE-MS method as most frequently practiced has significant, inherent limitations. First, the combination of limited sample capacity and limited detection sensitivity of 2DE restricts the detection of low abundance proteins. If total yeast cell lysates are separated and detected by silver staining, proteins present at less than 1000 copies per cell are not detected (44Gygi S.P. Y. Y. Aebersold R. Proc. Natl. Acad. Sci. U. S. A. 2000; PubMed Scopus Google Scholar). proteins at low abundance a of a proteome (44Gygi S.P. Y. Y. Aebersold R. Proc. Natl. Acad. Sci. U. S. A. 2000; PubMed Scopus Google Scholar), is apparent that the proteins detected by 2DE not a of the proteins. advances T. C. A. J. Electrophoresis. 1997; 18: PubMed Scopus Google Scholar, A. C. G. A. B. R. W. Electrophoresis. 2000; PubMed Scopus Google Scholar), the of proteins by 2DE a of contain more than protein and/or or of a protein that to different in the quantification (44Gygi S.P. Y. Y. Aebersold R. Proc. Natl. Acad. Sci. U. S. A. 2000; PubMed Scopus Google Scholar). the method is the identification of protein the method is and a high the potential for these indicate the for the development of or proteome analysis is to become a these of the 2DE-MS approach have been that include sample to 2DE A.A. Electrophoresis. 1997; 18: PubMed Scopus Google Scholar), the use of protein with detection sensitivity E. K. Electrophoresis. 2000; PubMed Scopus Google Scholar), and the use of with A. C. G. A. B. R. W. Electrophoresis. 2000; PubMed Scopus Google Scholar, R. A. C. G. W. S.J. A. Electrophoresis. 2000; PubMed Scopus Google Scholar) to the detection sensitivity of low abundance the search for new to of proteins T. C. A. J. Electrophoresis. 1997; 18: PubMed Scopus Google Scholar), and the development of and to the level of of the (42Blackstock W. Mann M. Blackstock W. Proteomics: a Trends Guide. Elsevier, London2000: 12-17Google Scholar, Electrophoresis. 2000; PubMed Scopus Google Scholar). an technique has been emerging that has the potential to and the proteins in a cell or tissue It is The is protein identification by automated tandem mass spectrometry and sequence data base the same methods developed for the identification of proteins are to the of protein The is the of the of abundance for proteins present in different protein samples by stable isotope isotope dilution theory L.M. Mass Spectrom. Rev. 1992; Scopus Google Scholar) states that the in a mass of two analytes that are of different stable isotope composition in a mass are a of the abundance of the two analytes in the The is the targeted isolation of selected peptide analytes complex peptide mixtures specific chemical the the measurement of abundance and the identification of the of complex protein mixtures and with a high of without the to separate protein mixtures to analysis. of technology also have the potential to and of proteins that their functional These include the state and the of of The and early applications of proteomics technology are described The challenge comprehensive proteomics approach is of and complex mixtures of proteins in in abundance by or more of information to for comprehensive of proteins. the combination of selective of proteins with stable affinity and multidimensional liquid chromatography in with automated, data-dependent tandem mass spectrometry and sequence data base has and has been to at of the of the approach to proteomics. The of proteins at specific in a complex by and selective of the peptide has to an method for the analysis of protein The contained in the of is a targeted for the and of proteins and peptides Methods Enzymol. PubMed Scopus Google S. Chait B.T. Anal. Chem. 1998; PubMed Scopus Google Scholar). The of in protein sequences an to for the of the of peptide mixtures of peptides in the yeast contain a D. J. Chait B.T. Electrophoresis. 1998; 19: PubMed Scopus Google as of the total proteins in the S. contain at D. J. Chait B.T. Electrophoresis. 1998; 19: PubMed Scopus Google Scholar), and identification of the peptides the comprehensive identification of the of the sample is of the of peptide mixtures to mass spectrometric analysis is for several First, the of a of the peptides by of a protein the of the selected peptides in the sample that is the The of the sample by selective is for and low abundance proteins. as low peptides are automated MS/MS analysis to the long of the the for the identification of a of the the of the that is indicated by the specific between the and the a for sequence data base The use of selective of for the of the peptide samples by of protein mixtures to mass spectrometric analysis has been by Spahr et al. C.S. S.A. Robinson J.H. Davis M.T. M.D. G. Patterson S.D. Electrophoresis. 2000; PubMed Scopus Google Scholar). The using a and these peptides were using and by This experiment was of a in a total of proteins samples were and of peptides is also the of the isotope-coded affinity tag approach that was developed in S.P. B. S.A. F. Aebersold R. Nat. 1999; PubMed Scopus Google Scholar). approach the proteins present in two samples the proteins by a cell two different are the of their using of two different of the is an the to as the and the other is an the have been replaced with the of peptide with and of the are to stable isotope dilution theory L.M. Mass Spectrom. Rev. 1992; Scopus Google Scholar) as for accurate protein The of each protein present in the two biological samples is by the of of peptides using an mass The identification of the proteins is accomplished by the to MS/MS in peptides for for quantitative protein analysis using selective peptide and MS have also been developed M. M. G. P. Anal. Chem. 2000; 72: PubMed Scopus Google Scholar, J. A. M. X. A. M. F. J. 2000; PubMed Scopus Google Scholar). et al. M. M. G. P. Anal. Chem. 2000; 72: PubMed Scopus Google Scholar) the of peptides proteins using a stable to the of protein expression in of these peptides mass that de peptide by MS/MS analysis sequence interpretation of MS/MS spectra without the for data base approach the of peptides with or for quantification of protein expression and de approach to quantitative protein analysis of stable into proteins cell or or in stable Y. K. Cross D. Chait B.T. Proc. Natl. Acad. Sci. U. S. A. 1999; PubMed Scopus Google Scholar, L. Jensen P. G. M. K. S. N. J. Smith R. J. Am. Chem. Soc. 1999; Scopus Google Scholar). with selective and of that liquid chromatography in with automated ESI tandem mass spectrometric analysis have been developed as an to 2DE for complex protein mixtures Yates J.R. Mann M. Blackstock W. Proteomics: a Trends Guide. Elsevier, London2000: Scholar, Lewis J.W. Anal. Chem. 1997; 69: PubMed Scopus (325) Google Scholar, Eng J. Schieltz D.M. E. D.R. Yates J.R. Nat. 1999; PubMed Scopus Google Scholar). et al. Eng J. Schieltz D.M. E. D.R. Yates J.R. Nat. 1999; PubMed Scopus Google Scholar) described an that a two-dimensional with strong cation exchange and of peptides by and by by MS/MS analysis. This method has for the comprehensive analysis of protein Eng J. Schieltz D.M. E. D.R. Yates J.R. Nat. 1999; PubMed Scopus Google Scholar), and more has been to the identification of low abundance a yeast D. Yates III, J.R. Nat. 2001; 19: PubMed Scopus Google Scholar). et al. (44Gygi S.P. Y. Y. Aebersold R. Proc. Natl. Acad. Sci. U. S. A. 2000; PubMed Scopus Google Scholar) have a approach that high performance liquid chromatography in with MS/MS and have that method the analysis of low abundance proteins in S. that are not sensitive to have also multidimensional with the described to an approach to the quantitative analysis of protein expression have to the of in the protein expression in yeast cells S.P. B. S.A. F. Aebersold R. Nat. 1999; PubMed Scopus Google Scholar) to in the protein composition in cells D.K. Eng J. H. Aebersold R. Nat. 2001; 19: PubMed Scopus Google Scholar), as as to differences in protein and cell E. and R. in by protein expression data with array data the corresponding mRNA expression have the tools for the analysis of gene expression a level. an have these two gene expression to the analysis of pathways in yeast T. Thorsson V. Ranish J.A. Christmas R. Buhler J. Eng J.K. Bumgarner R. Goodlett D.R. Aebersold R. Hood L. Science. 2001; 292: 929-934Crossref PubMed Scopus (1649) Google Scholar). It that the approach as as proteomics to and the These advances by and to mass is to proteomics The combination of stable isotope and automated MS/MS also to and of other than their have developed a method for the quantitative analysis of protein a H. Aebersold R. Nat. 2001; 19: PubMed Scopus Google Scholar). It the specific of the isolation of these for mass spectrometric analysis using a This method also a of the of the peptides with stable isotope the quantitative analysis of proteins by MS/MS in a to the This approach to the proteins contained in a total yeast cell in a MS/MS experiment many of were not to proteins. The development of Y. Proc. Natl. Acad. Sci. U. S. A. 1999; PubMed Scopus Google Scholar, M.A. 1999; PubMed Scopus Google Scholar, D. Burlingame A. M. Chem. Biol. 2000; 7: Full Text Full Text PDF PubMed Scopus Google Scholar) that proteins their state of rather than the of specific an opportunity to Chem. Biol. 2000; 4: PubMed Scopus Google Scholar). This is by the of chemical that to the of specific in an et al. Y. Proc. Natl. Acad. Sci. U. S. A. 1999; PubMed Scopus Google Scholar) have developed a that the of and et al. D. Burlingame A. M. Chem. Biol. 2000; 7: Full Text Full Text PDF PubMed Scopus Google Scholar) have developed an for the selective of with stable isotope the of the and of selected of proteins by It that to the performance of mass detection sample mass and mass to not the same The of a mass that a with a a cell and a A.V. M. W. Mass Spectrom. 2000; 14: PubMed Scopus Google Scholar, A. A. Shevchenko A. W. Anal. Chem. 2000; 72: PubMed Scopus Google Scholar) the to the to and mass of MALDI-TOF MS with the of have the to for the analysis of proteins A. S.P. B. A. W. Aebersold R. Anal. Chem. 2001; PubMed Scopus Google Scholar) with the of the approach being that proteins expression between the two biological by MS/MS analysis, or differences in expression The to the proteins to a in throughput for protein expression in is the development of a mass J.M. Baldwin M.A. P. M.L. Burlingame A.L. Anal. Chem. 2000; 72: PubMed Scopus Google Scholar). This the same of the with the potential for analysis and the potential to sample the identification of of proteins per type of that potential for is the mass and mass to other mass L. Jensen P. G. M. K. S. N. J. Smith R. J. Am. Chem. Soc. 1999; Scopus Google Scholar, S.E. Shabanowitz J. Hunt D.F. Marto J.A. Anal. Chem. 2000; 72: PubMed Scopus Google Scholar, J. R. Smith Anal. Chem. 1999; PubMed Scopus Google Scholar). It has been in yeast that with the mass by analysis of peptides is to the peptides the proteins are a data base without the for tandem mass spectrometric analysis D.R. B. L. O. Smith Aebersold R. Anal. Chem. 2000; 72: PubMed Scopus Google Scholar, T.D. L. Smith Anal. Chem. 2000; 72: PubMed Scopus Google Scholar). This for the detection of low abundance proteins that are many when peptides by MS/MS and approach has for sensitivity and throughput in these advances are to the performance of with respect to level of sample and that the to measure of proteins proteomics to the comprehensive analysis of biological Goodlett for
Source: Journal of Biological Chemistry
Authors: Timothy J. Griffin, Ruedi Aebersold
Institution: Institute for Systems Biology
Language: English
Subfield: Spectroscopy
Field: Chemistry
Domain: Physical Sciences
Open Access status: hybrid
Estimated APC paid: $3,430
OpenAlex ID: W1990142733