La RMN en el estudio del metaboloma humano: Definiciones y aspectos prácticos
Palabras clave:
metabolómica, resonancia magnética nuclear, identificación de metabolitos, RMN cuantitativa, PCA, PLS-DASinopsis
El metaboloma humano es una vasta colección de moléculas de bajo peso molecular como lípidos, péptidos, ácidos orgánicos, carbohidratos, aminoácidos y nucleótidos que actúan como sustratos o productos del metabolismo y que están relacionadas con funciones celulares esenciales como, nutrición, crecimiento y reproducción, diferenciación, señalización y apoptosis. El análisis integral del metaboloma es el tema central del enfoque de la metabolómica, y desde una orientación aplicada a las ciencias biomédicas y la investigación clínica, constituye una herramienta muy valiosa para conocer de forma global los procesos patológicos y conducir al descubrimiento de biomarcadores de diagnóstico, progresión y pronóstico de evolución. La RMN es una herramienta analítica que destaca por su robustez y reproducibilidad, ya que permite la detección, identificación y cuantificación de múltiples matabolitos de forma simultánea. Esto hace que sea uno de los métodos más empleados en los estudios de metabolómica. Los datos obtenidos con RMN son posteriormente sometidos a análisis estadístico multivariable con la finalidad de extraer la información diferencial entre los grupos de estudio a partir de su metaboloma, y conducir a una descripción biológica de los procesos relacionados con patologías e identificar biomarcadores, evaluar cambios asociados a la nutrición o variaciones ambientales, entre otras posibilidades.
Capítulos
-
La RMN en el estudio del metaboloma humano: Definiciones y aspectos prácticos
Citas
Anderson, James R, Susama Chokesuwattanaskul, Marie M. Phelan, Tim J. M. Welting, Lu-Yun Lian, Mandy J. Peffers, y Helen L. Wright. 2018. “1H NMR Metabolomics Identifies Underlying Inflammatory Pathology in Osteoarthritis and Rheumatoid Arthritis Synovial Joints.” Journal of Proteome Research 17 (11): 3780-90. https://doi.org/10.1021/acs.jproteome.8b00455.
Barbosa, Banny Silva, Lucas Gelain Martins, Tássia B. B. C. Costa, Guilherme Cruz y Ljubica Tasic. 2018. “Qualitative and Quantitative NMR Approaches in Blood Serum Lipidomics.” Methods in Molecular Biology (Clifton, N.J.) 1735: 365-79. https://doi.org/10.1021/10.1007/978-1-4939-7614-0_25.
Benítez Del Castillo, José Manuel, Maria Dolores Pinazo-Duran, Silvia Sanz-González, Ana M. Muñoz-Hernández, Jose J. Garcia-Medina y Vicente Zanón-Moreno. 2021. “Tear 1H NMR-Based Metabolomics Application to the Molecular Diagnosis of Aqueous Tear Deficiency and Meibomian Gland Dysfunction.” Ophthalmic Research 64: 297-309. https://doi.org/10.1159/000510211.
Bhatia, Anil, Saurav J. Sarma, Zhentian Lei y Lloyd W Sumner. 2019. “UHPLC-QTOF-MS/MS-SPE-NMR: A Solution to the Metabolomics Grand Challenge of Higher-Throughput, Confident Metabolite Identifications.” Methods in Molecular Biology (Clifton, N.J.) 2037: 113-33. https://doi.org/10.1007/978-1-4939-9690-2_7.
Cambiaghi, Alice, Manuela Ferrario y Marco Masseroli. 2017. “Analysis of Metabolomic Data: Tools, Current Strategies and Future Challenges for Omics Data Integration.” Briefings in Bioinformatics 18 (3): 498-510. https://doi.org/10.1093/bib/bbw031.
Clish, Clary B. 2015. “Metabolomics: An Emerging but Powerful Tool for Precision Medicine.” Cold Spring Harbor Molecular Case Studies 1 (1): a000588-a000588. https://doi.org/10.1101/mcs.a000588.
Consonni, Roberto y Laura Ruth Cagliani. 2019. “The Potentiality of NMR-Based Metabolomics in Food Science and Food Authentication Assessment.” Magnetic Resonance in Chemistry?: MRC 57 (9): 558-78. https://doi.org/10.1002/mrc.4807.
Crook, Alexandra A. y Robert Powers. 2020. “Quantitative NMR-Based Biomedical Metabolomics: Current Status and Applications.” Molecules 25 (21): 5128. https://doi.org/10.3390/molecules25215128.
Dona, Anthony C., Michael Kyriakides, Flora Scott, Elizabeth A Shephard, Dorsa Varshavi, Kirill Veselkov y Jeremy R Everett. 2016. “A Guide to the Identification of Metabolites in NMR-Based Metabonomics/Metabolomics Experiments.” Computational and Structural Biotechnology Journal 14 (March): 135-53. https://doi.org/10.1016/j.csbj.2016.02.005.
Duarte, Iola F., Cristina Legido-Quigley, David A. Parker, Jonathan R Swann, Manfred Spraul, Ulrich Braumann, Ana M. Gil, et al. 2009. “Identification of Metabolites in Human Hepatic Bile Using 800 MHz 1H NMR Spectroscopy, HPLC-NMR/MS and UPLC-MS.” Molecular BioSystems 5 (2): 180-90. https://doi.org/10.1039/b814426e.
Dudzik, Danuta, Cecilia Barbas-Bernardos, Antonia García, y Coral Barbas. 2018. “Quality Assurance Procedures for Mass Spectrometry Untargeted Metabolomics. a Review.” Journal of Pharmaceutical and Biomedical Analysis 147: 149-73. https://doi.org/10.1016/j.jpba.2017.07.044.
Emwas, Abdul-Hamid, Claudio Luchinat, Paola Turano, Leonardo Tenori, Raja Roy, Reza M. Salek, Danielle Ryan, et al. 2015. “Standardizing the Experimental Conditions for Using Urine in NMR-Based Metabolomic Studies with a Particular Focus on Diagnostic Studies: A Review.” Metabolomics 11 (4): 872-94.
Emwas, Abdul-Hamid, Raja Roy, Ryan T McKay, Leonardo Tenori, Edoardo Saccenti, G. A. Nagana Gowda, Daniel Raftery, et al. 2019. “NMR Spectroscopy for Metabolomics Research.” Metabolites 9 (7). https://doi.org/10.1007/s11306-014-0746-7.
Emwas, Abdul-Hamid, Edoardo Saccenti, Xin Gao, Ryan T. McKay, Vitor A. P. Martins dos Santos, Raja Roy y David S Wishart. 2018. “Recommended Strategies for Spectral Processing and Post-Processing of 1D 1H-NMR Data of Biofluids with a Particular Focus on Urine.” Metabolomics 14 (3): 31. https://doi.org/10.1007/s11306-018-1321-4.
Euceda, Leslie R., Maria K. Andersen, May Britt Tessem, Siver A. Moestue, Maria T. Grinde y Tone F. Bathen. 2018. “NMR-Based Prostate Cancer Metabolomics.” In Methods in Molecular Biology, 1786:237-57. Humana Press Inc. https://doi.org/10.1007/978-1-4939-7845-8_14.
Ghini, Veronica, Deborah Quaglio, Claudio Luchinat y Paola Turano. 2019. “NMR for Sample Quality Assessment in Metabolomics.” New Biotechnology 52: 25-34. https://doi.org/10.1016/j.nbt.2019.04.004.
Gödecke, Tanja, José G. Napolitano, María F. Rodríguez-Brasco, Shao Nong Chen, Birgit U. Jaki, David C. Lankin y Guido F. Pauli. 2013. “Validation of a Generic Quantitative 1h NMR Method for Natural Products Analysis.” Phytochemical Analysis 24 (6): 581-97. https://doi.org/10.1002/pca.2436.
Grimaldi, Manuela, Angelica Palisi, Giuseppina Rossi, Ilaria Stillitano, Francesco Faiella, Paola Montoro, Manuela Rodriquez, Remo Palladino, Anna Maria D’Ursi y Rocco Romano. 2018. “Saliva of Patients Affected by Salivary Gland Tumour: An NMR Metabolomics Analysis.” Journal of Pharmaceutical and Biomedical Analysis 160 (October): 436-42. https://doi.org/10.1016/j.jpba.2018.08.015.
Haijes, Hanneke A., Marcel Willemsen, Maria Van der Ham, Johan Gerrits, Mia L. Pras-Raves, Hubertus C M T Prinsen, Peter M Van Hasselt, Monique G M De Sain-van der Velden, Nanda M. Verhoeven-Duif y Judith J. M. Jans. 2019. “Direct Infusion Based Metabolomics Identifies Metabolic Disease in Patients’ Dried Blood Spots and Plasma.” Metabolites 9 (1): 12. https://doi.org/10.3390/metabo9010012.
Hernandez-Baixauli, Julia, Sergio Quesada-Vázquez, Roger Mariné-Casadó, Katherine Gil Cardoso, Antoni Caimari, Josep M Del Bas, Xavier Escoté y Laura Baselga-Escudero. 2020. “Detection of Early Disease Risk Factors Associated with Metabolic Syndrome: A New Era with the NMR Metabolomics Assessment.” Nutrients 12 (3): 806. https://doi.org/10.3390/nu12030806.
Higgins-Keppler, Emily A., Carrie L. Jenkins, Trenton J. Davis y Heather D. Bean. 2018. “Advances in the Application of Comprehensive Two-Dimensional Gas Chromatography in Metabolomics.” TrAC Trends in Analytical Chemistry 109: 275-86. https://doi.org/10.1016/j.trac.2018.10.015.
Jacyna, Julia, Marta Kordalewska y Micha? J Markuszewski. 2019. “Design of Experiments in Metabolomics-Related Studies: An Overview.” Journal of Pharmaceutical and Biomedical Analysis 164: 598-606. https://doi.org/10.1016/j.jpba.2018.11.027.
Kang, Dae-Wook, Zehra Esra Ilhan, Nancy G. Isern, David W. Hoyt, Daniel P. Howsmon, Michael Shaffer, Catherine A. Lozupone, Juergen Hahn, James B. Adams y Rosa Krajmalnik-Brown. 2018. “Differences in Fecal Microbial Metabolites and Microbiota of Children with Autism Spectrum Disorders.” Anaerobe 49 (February): 121-31. https://doi.org/10.1016/j.anaerobe.2017.12.007.
Klassen, A., A. Tedesco Faccio, G.. Baptista Canuto, P. Rocha de la Cruz, H. Caracho Ribeiro, M. Maggi Tavarez y A Sussulini. 2017. “Metabolomics: Definitions and Significance in Systems Biology.” In Metabolomics: From Fundamentals to Clinical Applications. Advances in Experimental Medicine and Biology. Vol. 965., edited by A Sussulini, First Ed. Springer, Cham. https://doi.org/10.1007/978-3-319-47656-8_1.
López-Pacheco, M. C., C. Pimentel-Hernández, E. Rivas-Mirelles, y J. L. Arredondo-García. 2016. “Normatividad Que Rige La Investigación Clínica En Seres Humanos y Requisitos Que Debe Cumplir Un Centro de Investigación Para Participar En Un Estudio Clínico En México.” Acta Pediátrica de México 37 (3): 175-82. http://dx.doi.org/10.18233/APM37No3pp175-182.
Markley, John L., Hesam Dashti, Jonathan R. Wedell, William M. Westler, y Hamid R. Eghbalnia. 2019. “Tools for Enhanced NMR-Based Metabolomics Analysis.” Methods in Molecular Biology (Clifton, N.J.) 2037: 413-27. https://doi.org/10.1007/978-1-4939-9690-2_23.
Missailidis, Catharina, Jenny Hällqvist, Abdel Rashid Qureshi, Peter Barany, Olof Heimbürger, Bengt Lindholm, Peter Stenvinkel y Peter Bergman. 2016. “Serum Trimethylamine-N-Oxide Is Strongly Related to Renal Function and Predicts Outcome in Chronic Kidney Disease.” PloS One 11 (1): e0141738. https://doi.org/10.1371/journal.pone.0141738.
Murgia, Federica, Valentina Corda, Marianna Serrenti, Valeria Usai, Maria Laura Santoru, K Joseph Hurt, Mauro Passaretti, Maria Carla Monni, Luigi Atzori y Giovanni Monni. 2020. “Seminal Fluid Metabolomic Markers of Oligozoospermic Infertility in Humans.” Metabolites 10 (2): 64. https://doi.org/10.3390/metabo10020064.
Nicholson, Jeremy K, John C. Lindon, y Elaine Holmes. 1999. “‘Metabonomics’: Understanding the Metabolic Responses of Living Systems to Pathophysiological Stimuli via Multivariate Statistical Analysis of Biological NMR Spectroscopic Data.” Xenobiotica; the Fate of Foreign Compounds in Biological Systems 29 (11): 1181-89. https://doi.org/10.1080/004982599238047.
Nicholson, Jeremy K., Elaine Holmes y John C. Lindon. 2007. “Chapter 1 - Metabonomics and Metabolomics Techniques and Their Applications in Mammalian Systems.” In The Handbook of Metabonomics and Metabolomics, edited by John C Lindon, Jeremy K Nicholson y Elaine B T. Amsterdam: Elsevier Science B.V. Öhman, Anders, y Lars Forsgren. 2015. https://doi.org/10.1016/B978-044452841-4/50002-3.
Orczyk-Pawilowicz, Magdalena, Ewa Jawien, Stanislaw Deja, Lidia Hirnle, Adam Zabek y Piotr Mlynarz. 2016. “Metabolomics of Human Amniotic Fluid and Maternal Plasma during Normal Pregnancy.” PLOS ONE. 11 (4): 1-13. https://doi.org/10.1371/journal.pone.0152740.
Puchades-Carrasco, Leonor, y Antonio Pineda-Lucena. 2017. “Metabolomics Applications in Precision Medicine: An Oncological Perspective.” Current Topics in Medicinal Chemistry 17 (24): 2740-51. https://doi.org/10.2174/1568026617666170707120034.
Ramakrishnan, Venkatesh y Devanand L Luthria. 2017. “Recent Applications of NMR in Food and Dietary Studies.” Journal of the Science of Food and Agriculture 97 (1): 33-42. https://doi.org/https://doi.org/10.1002/jsfa.7917.
Reimand, Jüri, Ruth Isserlin, Veronique Voisin, Mike Kucera, Christian Tannus-Lopes, Asha Rostamianfar, Lina Wadi, et al. 2019. “Pathway Enrichment Analysis and Visualization of Omics Data Using g:Profiler, GSEA, Cytoscape and EnrichmentMap.” Nature Protocols 14 (2): 482-517. https://doi.org/10.1038/s41596-018-0103-9.
Roberts, Lee D., Amanda L. Souza, Robert E. Gerszten y Clary B. Clish. 2012. “Targeted Metabolomics.” Current Protocols in Molecular Biology Chapter 30: Unit 30.2.1-24. https://doi.org/10.1002/0471142727.mb3002s98.
Savorani, Francesco, Morten Arendt Rasmussen, Mette Skau Mikkelsen, y Søren Balling Engelsen. 2013. “A Primer to Nutritional Metabolomics by NMR Spectroscopy and Chemometrics.” Food Research International 54 (1): 1131-45. https://doi.org/10.1016/j.foodres.2012.12.025.
Schrimpe-Rutledge, Alexandra C., Simona G. Codreanu, Stacy D. Sherrod y John A. McLean. 2016. “Untargeted Metabolomics Strategies-Challenges and Emerging Directions.” Journal of the American Society for Mass Spectrometry 27 (12): 1897-1905. https://doi.org/10.1007/s13361-016-1469-y.
Smirnov, Kirill S., Tanja V. Maier, Alesia Walker, Silke S. Heinzmann, Sara Forcisi, Inés Martinez, Jens Walter y Philippe Schmitt-Kopplin. 2016. “Challenges of Metabolomics in Human Gut Microbiota Research.” International Journal of Medical Microbiology 306 (5): 266-79. https://doi.org/10.1016/j.ijmm.2016.03.006.
Souza, S. L., G. Graça y A. Oliva. 2018. “Characterization of Sweat Induced with Pilocarpine, Physical Exercise Collected Passively by Metabolomic Analysis.” Skin Research and Technology?: Official Journal of International Society for Bioengineering and the Skin (ISBS) [and] International Society for Digital Imaging of Skin (ISDIS) [and] International Society for Skin Imaging (ISSI) 24 (2): 187-95. https://doi.org/10.1111/srt.12412.
Sumner, Lloyd W., Alexander Amberg, Dave Barrett, Michael H. Beale, Richard Beger, Clare A. Daykin, Teresa W.-M. Fan, et al. 2007. “Proposed Minimum Reporting Standards for Chemical Analysis.” Metabolomics 3 (3): 211-21. https://doi.org/10.1007/s11306-007-0082-2.
Vicente-Muñoz, Sara, Teresa Cobo, Leonor Puchades-Carrasco, Ana B. Sánchez-García, Núria Agustí, Montse Palacio, Antonio Pineda-Lucena y Eduard Gratacós. 2020. “Vaginal Metabolome: Towards a Minimally Invasive Diagnosis of Microbial Invasion of the Amniotic Cavity in Women with Preterm Labor.” Scientific Reports 10 (1): 5465. https://doi.org/10.1038/s41598-020-62542-6.
Vilar-Compte, D. y E. Salazar-Rojas. 2013. “Capítulo 5: Estudios Experimentales. Ensayo Clínico Aleatorio.” In Epidemiología Clínica, edited by Laura Moreno-Altamirano, Tercera Ed. McGrawn Hill.
Villas-Boas, S. G., U. Roessner, M. A. E. Hansen, J. Smedsgaard y J. Nielsen. 2007. Metabolome Analysis: An Introduction. New Jersey, USA: Wiley-Interscience. https://doi.org/10.1002/0470105518.
Vu, Thao, Parker Siemek, Fatema Bhinderwala, Yuhang Xu, y Robert Powers. 2019. “Evaluation of Multivariate Classification Models for Analyzing NMR Metabolomics Data.” Journal of Proteome Research 18 (9): 3282-94. https://doi.org/10.1021/acs.jproteome.9b00227.
Watanabe, Ryuichi, Chika Sugai, Taichi Yamazaki, Ryoji Matsushima, Hajime Uchida, Masahiro Matsumiya, Akiko Takatsu, y Toshiyuki Suzuki. 2016. “Quantitative Nuclear Magnetic Resonance Spectroscopy Based on PULCON Methodology: Application to Quantification of Invaluable Marine Toxin, Okadaic Acid.” Toxins 8 (10). https://doi.org/10.3390/toxins8100294.
Wishart, David S. 2019. “NMR Metabolomics: A Look Ahead.” Journal of Magnetic Resonance 306: 155-61. https://doi.org/10.1016/j.jmr.2019.07.013.
Wu, Junfang, Magnus Domellöf, Angela M Zivkovic, Göran Larsson, Anders Öhman, y Malin L. Nording. 2016. “NMR-Based Metabolite Profiling of Human Milk: A Pilot Study of Methods for Investigating Compositional Changes during Lactation.” Biochemical and Biophysical Research Communications 469 (3): 626-32. https://doi.org/10.1016/j.bbrc.2015.11.114.
Zacharias, Helena U., Michael Altenbuchinger, y Wolfram Gronwald. 2018. “Statistical Analysis of NMR Metabolic Fingerprints: Established Methods and Recent Advances.” Metabolites 8 (3). https://doi.org/10.3390/metabo8030047