Proteômica: uma introdução aos métodos e aplicações

Autores

  • Nayara Braga Emidio Universidade Federal de Juiz de Fora http://orcid.org/0000-0001-7835-9636
  • Arthur Girardi Carpanez Universidade Federal de Juiz de Fora
  • Leonardo Ramos Quellis Universidade Federal de Juiz de Fora
  • Priscila Silva Farani Universidade Federal de Juiz de Fora
  • Eveline Gomes Vasconcelos Universidade Federal de Juiz de Fora
  • Priscila Faria-Pinto Universidade Federal de Juiz de Fora http://orcid.org/0000-0002-9011-2027

Palavras-chave:

Proteômica, Espectrometria de Massas, Peptídeos, Proteínas, Biomarcadores

Resumo

As proteínas desempenham a maior parte das funções fisiológicas das células, constituindo também importantes alvos farmacológicos e biomarcadores de doenças. A pesquisa qualitativa, quantitativa e a elucidação estrutural destas moléculas são fundamentais para a compreensão do funcionamento dos sistemas biológicos, bem como na aplicação destas para o desenvolvimento de novos métodos diagnóstico. O estudo do proteoma nos permite identificar as proteínas que estão sendo expressas em um determinado momento, quantificá-las e observar suas modificações pós-transducionais. Dessa maneira, a análise proteômica fornece informações mais abrangentes e que não podem ser inferidas a partir das informações obtidas através da análise genômica. Este tipo de estudo envolve etapas como: extração e tratamento da amostra, separação das proteínas e/ou peptídeos, espectrometria de massas e análise dos dados usando ferramentas de bioinformática. O presente trabalho faz uma revisão narrativa sobre as principais técnicas aplicadas desde o preparo de amostras até a identificação das proteínas. 

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Biografia do Autor

Nayara Braga Emidio, Universidade Federal de Juiz de Fora

Laboratório de Estrutura e Função de Proteínas/ Departamento de Bioquímica/Instituto de Ciências Biológicas

Arthur Girardi Carpanez, Universidade Federal de Juiz de Fora

Departamento de Química/Instituto de Ciências Exatas

Leonardo Ramos Quellis, Universidade Federal de Juiz de Fora

Laboratório de Estrutura e Função de Proteínas/ Departamento de Bioquímica/Instituto de Ciências Biológicas

Priscila Silva Farani, Universidade Federal de Juiz de Fora

Laboratório de Estrutura e Função de Proteínas/ Departamento de Bioquímica/Instituto de Ciências Biológicas

Eveline Gomes Vasconcelos, Universidade Federal de Juiz de Fora

Laboratório de Estrutura e Função de Proteínas/ Departamento de Bioquímica/Instituto de Ciências Biológicas

Priscila Faria-Pinto, Universidade Federal de Juiz de Fora

Laboratório de Estrutura e Função de Proteínas/ Departamento de Bioquímica/Instituto de Ciências Biológicas

Referências

ALTELAAR, A. F.; MUNOZ, J.; HECK, A. J. Next-generation proteomics: towards an integrative view of proteome dynamics. Nature Reviews Genetics, London, v. 14, no. 1, p. 35-48, Jan 2013.

ARN, P. H. Phenylketonuria (PKU). In: Aminoff, M. J. e Daroff, R. B. Encyclopedia of the Neurological Sciences (Second Edition). Oxford: Academic Press, 2014, p.887-889.

AVEZUM, Á. et al. III Diretriz sobre tratamento do infarto agudo do miocárdio. Arquivos Brasileiros de Cardiologia, Rio de Janeiro, v. 83, n.4, p. 1-86, Set 2004.

BAKER, E. S. et al. Mass spectrometry for translational proteomics: progress and clinical implications. Genome Medicine, London, v. 4, no. 8, p. 63, Sep 2012.

BENSIMON, A.; HECK, A. J.; AEBERSOLD, R. Mass spectrometry-based proteomics and network biology. Annual Review of Biochemistry, Palo Alto, v. 81, no. 1, p. 379-405, Jul 2012.

CARVALHO, P. C., FISHER, J. S. G., WIM M. DEGRAVE, W. M., CARVALHO, M. G. C.. Marcadores séricos e espectrometria de massa no diagnóstico do cancer. Jornal Brasileiro de Patologia e Medicina Laboratorial, Rio de Janiero, v. 42, n. 6, p. 6, Dez 2006.

CARVALHO, P. C.; YATES III, J. R.; BARBOSA, V. C. Analyzing Shotgun Proteomic Data with PatternLab for Proteomics. In: (Ed.). Current Protocols in Bioinformatics: John Wiley & Sons, Inc., 2010.

CATHERMAN, A. D.; SKINNER, O. S.; KELLEHER, N. L. Top Down proteomics: Facts and perspectives. Biochemical and Biophysical Research Communications, New York, v. 445, no. 4, p. 683-693, Mar 2014.

CERCIELLO, F.; CHOI, M.; NICASTRI, A.; BAUSCH-FLUCK, D.; ZIEGLER, A.; VITEK, O.; FELLEY-BOSCO, E.; STAHEL, R.; AEBERSOLD, R.; WOLLSCHEID, B. Identification of a seven glycopeptide signature for malignant pleural mesothelioma in human serum by selected reaction monitoring. Clinical Proteomics, London, v. 10, no. 1, p. 1-12, Nov 2013.

CHEVALIER, F. Highlights on the capacities of "Gel-based" proteomics. Proteome Science, London, v. 8, no. 23, Apr 2010.

COHEN, S. L., CHAIT, B. T., Influence of matrix solution conditions on the MALDI-MS analysis of peptides and proteins. Analytical Chemistry, Washington, v. 68, no. 1, p. 31-37, Jan 1996.

CHI, H.; CHEN, H.; HE, K.; WU, L.; YANG, B.; SUN, R. X.; LIU, J.; ZENG, W. F.; SONG, C. Q.; HE, S. M.; DONG, M. Q. pNovo+: de novo peptide sequencing using complementary HCD and ETD tandem mass spectra. Journal of proteome research, Washington, v. 12, no. 2, p. 615-625, Dec 2013.

CHO, W. C. Proteomics in translational cancer research: biomarker discovery for clinical applications. Expert Review of Proteomics, London, v. 11, no. 2, p. 131-133, Apr 2014.

DEUTSCH, E. W.; MENDOZA, L.; SHTEYNBERG, D.; FARRAH, T.; LAM, H.; TASMAN, N.; SUN, Z.; NILSSON, E.; PRATT, B.; PRAZEN, B.; ENG, J. K.; MARTIN, D. B.; NESVIZHSKII, A. I.; AEBERSOLD, R. A guided tour of the Trans-Proteomic Pipeline. Proteomics, London, v. 10, no. 6, p. 1150-1159, Mar 2010.

DI PALMA, S et al. Recent advances in peptide separation by multidimensional liquid chromatography for proteome analysis. Journal of Proteomics, London, v. 75, no. 13, p. 3791-3813, Jul 2012.

EDMOND DE HOFFMANN, V. S. Mass Spectrometry: Principles and Applications: Wiley, 2001

EL-ANEED, A.; COHEN, A.; BANOUB, J. Mass Spectrometry, Review of the Basics: Electrospray, MALDI, and Commonly Used Mass Analyzers. Applied Spectroscopy Reviews, v. 44, no. 3, p. 210-230, Oct 2009.

FRANK, A.; PEVZNER, P. PepNovo: de novo peptide sequencing via probabilistic network modeling. Analytical Chemistry, Washington, v. 77, no. 4, p. 964-973, Jan 2005.

FENN, J. B.; MANN, M.; MENG, C. K.; WONG, S. F.; WHITEHOUSE, C. M. Electrospray ionization for mass spectrometry of large biomolecules. Science, New York, v. 246, no. 4926, p. 64-71, Oct 1989.

FUZERY, A. K.; LEVIN, J.; CHAN, M. M.; CHAN, D. W. Translation of proteomic biomarkers into FDA approved cancer diagnostics: issues and challenges. Clinical Proteomics, London, v. 10, no. 1, p. 13, Oct 2013.

GASKELL, S. J. Electrospray: Principles and Practice. Journal of Mass Spectrometry, Chichester, v. 32, no. 7, p. 677-688, Jul 1997.

GHAZALPOUR, A. et al. Comparative analysis of proteome and transcriptome variation in mouse. PLoS Genetics, San Francisco, v. 7, no. 6, Jun 2011.

GLISH, G. L.; VACHET, R. W. The basics of mass spectrometry in the twenty-first century. Nature Reviews Drug Discovery, London, v. 2, no. 2, p. 140-150, Feb 2003.

HAN, X.; ASLANIAN, A.; YATES, J. R., 3RD. Mass spectrometry for proteomics. Current Opinion in Chemical Biology, London, v. 12, no. 5, p. 483-490, Aug 2008.

HEIN, M. Y. et al. Chapter 1 - Proteomic Analysis of Cellular Systems. In: Walhout, A. J. M., Vidal, M., et al . Handbook of Systems Biology. San Diego: Academic Press, 2013, p.3-25.

HO, C. S. et al. Electrospray Ionisation Mass Spectrometry: Principles and Clinical Applications. The Clinical Biochemist Reviews, Chippendale, v. 24, no. 1, p. 3-12, Feb 2003.

HU, Q. et al. The Orbitrap: a new mass spectrometer. Journal of mass spectrometry, Chichester, v. 40, no. 4, p. 430-43, Apr 2005.

HUGHES, C.; MA, B.; LAJOIE, G. A. De novo sequencing methods in proteomics. Methods in molecular biology, Totowa, v. 604, no., p. 105-121, 2010.

HÜTTENHAIN, R.; SOSTE, M.; SELEVSEK, N.; RÖST, H.; SETHI, A.; CARAPITO, C.; FARRAH, T.; DEUTSCH, E. W.; KUSEBAUCH, U.; MORITZ, R. L.; NIMÉUS-MALMSTRÖM, E.; RINNER, O.; AEBERSOLD, R. Reproducible quantification of cancer-associated proteins in body fluids using targeted proteomics. Science translational medicine, Washington, v. 4, no. 142, p. 142ra194, Sep 2012.

IMMING, P.; SINNING, C.; MEYER, A. Drugs, their targets and the nature and number of drug targets. Nature Reviews Drug Discovery, London, v. 5, no. 10, p. 821-834, Oct 2006.

JEONG, K.; KIM, S.; PEVZNER, P. A. UniNovo: a universal tool for de novo peptide sequencing. Bioinformatics, Oxford, v. 29, n. 16, p. 1953-1962, Aug 2013.

KARAS, M.; HILLENKAMP, F. Laser desorption ionization of proteins with molecular masses exceeding 10,000 daltons. Analytical Chemistry, Washington, v. 60, no. 20, p. 2299-2301, Oct 1988.

KELLIE, J. F.; TRAN, J. C.; LEE, J. E.; AHLF, D. R.; THOMAS, H. M.; NTAI, I.; CATHERMAN, A. D.; DURBIN, K. R.; ZAMDBORG, L.; VELLAICHAMY, A.; THOMAS, P. M.; KELLEHER, N. L. The emerging process of Top Down mass spectrometry for protein analysis: Biomarkers, protein-therapeutics, and achieving high throughput. Molecular BioSystems, Cambridge, v. 6, no. 9, p. 1532-1539, Sep 2010.

KINGDON, K. H. A Method for the Neutralization of Electron Space Charge by Positive Ionization at Very Low Gas Pressures. Physical Review, Schenectady v. 21, nO. 4, p. 408-418, Jan 1923.

KNOCHENMUSS, R.; ZENOBI, R. MALDI ionization: the role of in-plume processes. Chemical Reviews, Washington, v. 103, no. 2, p. 441-452, Feb 2003.

KOHLBACHER, O.; REINERT, K.; GROPL, C.; LANGE, E.; PFEIFER, N.; SCHULZ-TRIEGLAFF, O.; STURM, M. TOPP--the OpenMS proteomics pipeline. Bioinformatics, Oxford, v. 23, no. 2, p. e191-197, Jan 2007.

LIU, H.; LIN, D.; YATES, J. R., 3RD. Multidimensional separations for protein/peptide analysis in the post-genomic era. Biotechniques, London, v. 32, no. 4, p. 898-902, Apr 2002.

LEPREVOST, F. V.; VALENTE, R. H.; LIMA, D. B.; PERALES, J.; MELANI, R.; YATES, J. R., 3RD; BARBOSA, V. C.; JUNQUEIRA, M.; CARVALHO, P. C. PepExplorer: a similarity-driven tool for analyzing de novo sequencing results. Molecular & cellular proteomics : MCP, Bethesda v. 13, no. 9, p. 2480-2489, Sep 2014.

LOPEZ, E.; MADERO, L.; LOPEZ-PASCUAL, J.; LATTERICH, M. Clinical proteomics and OMICS clues useful in translational medicine research. Proteome Scince, London, v. 10, no. 1, p. 35, May 2012.

MA, B.; ZHANG, K.; HENDRIE, C.; LIANG, C.; LI, M.; DOHERTY-KIRBY, A.; LAJOIE, G. PEAKS: powerful software for peptide de novo sequencing by tandem mass spectrometry. Rapid communications in mass spectrometry : RCM, Chichester, v. 17, no. 20, p. 2337-2342, Oct 2003.

MCDONALD, W. H.; YATES, J. R., 3RD. Shotgun proteomics: integrating technologies to answer biological questions. Current opinion in molecular therapeutics, London, v. 5, no. 3, p. 302-309, Jun 2003.

MCLAFFERTY, F. "Tandem mass spectrometry.". Science, New York, v. 214, no. 4518, p. 280-287, 1981.

MAKAROV, A. Electrostatic Axially Harmonic Orbital Trapping: A High-Performance Technique of Mass Analysis. Analytical Chemistry, Manchester v. 72, no. 6, p. 1156-1162, Mar 2000.

MALLICK, P.; KUSTER, B. Proteomics: a pragmatic perspective. Nature Biotechnology, New York, v. 28, no. 7, p. 695-709, Jul 2010.

MANN, M.; HENDRICKSON, R. C.; PANDEY, A. Analysis of proteins and proteomes by mass spectrometry. Annual Review of Biochemistry, Palo Alto, v. 70, no. 1, p. 437-473, Jul 2001.

O'FARRELL, P. H. High Resolution Two-Dimensional Electrophoresis of Proteins. The Journal of biological chemistry, Baltimore, v. 250, no. 10, p. 4007-4021, May 1975.

OVERALL, C. M. Can proteomics fill the gap between genomics and phenotypes? Journal of Proteomics, Amsterdam, v. 100, p. 1-2, Apr 2014.

PAREEK, C. S.; SMOCZYNSKI, R.; TRETYN, A. Sequencing technologies and genome sequencing. Journal of Applied Genetics, Poznań, v. 52, no. 4, p. 413-435, Nov 2011.

PATEL, R. MALDI-TOF mass spectrometry: transformative proteomics for clinical microbiology. Clinical Chemistry, Washington, v. 59, no. 2, p. 340-342, Feb 2013.

CARVALHO, P. C., FISHER, J. S. G., WIM M. DEGRAVE, W. M., CARVALHO, M. G. C.. Marcadores séricos e espectrometria de massa no diagnóstico do cancer. Jornal Brasileiro de Patologia e Medicina Laboratorial, Rio de Janiero, v. 42, n. 6, p. 6, Dez 2006.

PAULO, J. A.; KADIYALA, V.; BANKS, P. A.; STEEN, H.; CONWELL, D. L. Mass spectrometry-based proteomics for translational research: a technical overview. Yale Journal of Biology and Medicine, New Haven, v. 85, no. 1, p. 59-73, Mar 2012.

PERRY, R. H.; COOKS, R. G.; NOLL, R. J. Orbitrap mass spectrometry: instrumentation, ion motion and applications. Mass spectrometry reviews, New York v. 27, no. 6, p. 661-99, Nov-Dec 2008.

POMASTOWSKI, P.; BUSZEWSKI, B. Two-dimensional gel electrophoresis in the light of new developments. Trends in Analytical Chemistry, Amsterdam, v. 53, p. 167-177, Jan 2014.

RABILLOUD, T.; LELONG, C. Two-dimensional gel electrophoresis in proteomics: A tutorial. Journal of Proteomics, Amsterdam, v. 74, no. 10, p. 1829-1841, Jun 2011.

SANCHEZ, J.-C. The art of proteomics translation. Translational Proteomics, Amsterdam, v. 1, no. 1, p. 1-2, 2013.

SHEVCHENKO, A.; SUNYAEV, S.; LOBODA, A.; SHEVCHENKO, A.; BORK, P.; ENS, W.; STANDING, K. G. Charting the proteomes of organisms with unsequenced genomes by MALDI-quadrupole time-of-flight mass spectrometry and BLAST homology searching. Analytical chemistry, Washington, v. 73, no. 9, p. 1917-1926, May 2001.

TANAKA, K.; WAKI, H.; IDO, Y.; AKITA, S.; YOSHIDA, Y.; YOSHIDA, T.; MATSUO, T. Protein and polymer analyses up to m/z 100 000 by laser ionization time-of-flight mass spectrometry. Rapid Communications in Mass Spectrometry, London, v. 2, no. 8, p. 151-153, Aug 1988.

THOMPSON, J.J.; Rays of Positive Electricity and their Application to Chemical Analysis. London: Longmans, Green and Co. Ltd., 1913.

WEATHERALL, D. J. Sickle Cell Anemia. In: Hughes, S. M. Brenner's Encyclopedia of Genetics (Second Edition). San Diego: Academic Press, 2013, p.429-431.

WOLTERS, D. A.; WASHBURN, M. P.; YATES, J. R., 3RD. An automated multidimensional protein identification technology for shotgun proteomics. Analytical chemistry, Washington, v. 73, no. 23, p. 5683-5690, Dec 2001.

YATES, J. R.; RUSE, C. I.; NAKORCHEVSKY, A. Proteomics by Mass Spectrometry: Approaches, Advances, and Applications. Annual Review of Biomedical Engineering, Palo Alto, v. 11, no. 1, p. 49-79, Apr 2009.

YATES, J. R., 3RD. Mass spectral analysis in proteomics. Annual review of biophysics and biomolecular structure, Palo Alto, v. 33, no., p. 297-316, Jun 2004.

ZHANG, Y.; FONSLOW, B. R.; SHAN, B.; BAEK, M. C.; YATES, J. R., 3RD. Protein analysis by shotgun/bottom-up proteomics. Chemical Reviews, Washington, v. 113, no. 4, p. 2343-2394, Apr 2013.

ZUBAREV, R. A.; MAKAROV, A. Orbitrap Mass Spectrometry. Analytical Chemistry, Washington v. 85, no. 11, p. 5288-5296, Apr 2013.

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2016-04-19

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Braga Emidio N, Girardi Carpanez A, Ramos Quellis L, Silva Farani P, Gomes Vasconcelos E, Faria-Pinto P. Proteômica: uma introdução aos métodos e aplicações. HU Rev [Internet]. 19º de abril de 2016 [citado 2º de novembro de 2024];41(3 e 4). Disponível em: https://periodicos.ufjf.br/index.php/hurevista/article/view/2482

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