Metabolomik çalışmalar, son yıllarda ortaya çıkan bilimsel ve teknolojik gelişmelerle beraber hastalıkların erken teşhis ve tedavisi başta olmak üzere çok çeşitli araştırma alanlarında kendine yer bulmuştur. Metabolitler insan vücudunda meydana gelen biyokimyasal reaksiyonlara katılan veya bu reaksiyonlar sonucu ortaya çıkan, düşük molekül ağırlıklı kimyasal bileşenlere verilen genel addır. Vücutta bulunan metabolitlerin tümü, metabolom terimi ile ifade edilir. Metabolomik ise mümkün olduğunca fazla sayıda metabolitin, ileri analitik teknikler ile ölçülmesidir. İlgili sonuçlar istatistiksel olarak değerlendirilir ve hastalık durumu veya tedavi şekli gibi belirlenen bir değişken üzerinden kontrol grubuyla karşılaştırılır. Böylece metabolom düzeyindeki değişim ortaya çıkarılır, miktarı değişen metabolitler tespit edilir ve hastalık durumundan etkilenen metabolik yolaklar tanımlanabilir. Metabolomik çalışmalar, metabolom düzeyi ile ilgili anlık bilgi sağlayabilmesi sayesinde genom düzeyinde aydınlatılan genotipe ek olarak fenotipin metabolom düzeyinde incelenebilmesini sağlar. Bu çalışma; metabolomik çalışmaların kökenleri, bugünkü durumu ve gelecekte oynayabileceği roller üzerine hazırlanmış bir derlemedir. Günümüzde metabolom düzeyinde biyobelirteç keşfi için yaygın olarak gerçekleştirilen sıvı kromatografisi-kütle spektrometrisi (LC-MS) temelli hedeflenmemiş metabolomik çalışmalarda yaşanan güncel problemler de bu derleme kapsamında değerlendirilmiştir. Özellikle kanser araştırmalarında sıklıkla söz edilmeye başlanan sıvı biyopsi tanımını uygulamaya geçirmek için klinik uygulamalarda metabolom düzeyinde gerçekleştirilecek çalışmalar büyük önem arz etmektedir. Yakın gelecekte hedeflenmemiş metabolomik çalışmalar sonucu elde edilen bilgi hedeflenmiş çalışmalar ile valide edilerek metabolom düzeyinde farklı hastalıklar için erken tanı ve süreç inceleme amacıyla kullanılabilecek çok sayıda yeni biyobelirteç klinik uygulamalarda kendine yer bulacaktır.
Anahtar Kelimeler: Metabolomik; metabolom; sistem biyolojisi; biyokimyasal olaylar
Along with the scientific and technological developments that have emerged in recent years, metabolomic studies have found themselves a place in a wide range of research fields especially including early diagnosis and treatment of diseases. Metabolites are the general names given to low molecular weight chemical components that participate in biochemical reactions or occurring as a result of biochemical reactions in the human body. The term metabolome is used to refer to all the metabolites found in the system of a body. Metabolomics is the measurement of as many metabolites as possible using advanced analytical techniques. The relevant results are evaluated statistically and compared with the control group over a determined variable such as disease status or treatment method. Thus, the change in the metabolome level is clarified, the amount of metabolites that are varying are determined and the metabolic pathways affected by the disease condition can be identified. Metabolomic research provides insight into the metabolome level, allowing the phenotype to be examined at metabolome level in addition to the genotype illuminated at genome level. This study is about the historical development of metabolomic studies, the current situation on metabolomic studies and the roles it could play in future. Current problems experienced in liquid chromatography-mass spectrometry (LC-MS) based untargeted metabolomic studies, which are widely performed for biomarker discovery at metabolome level, are also evaluated within the scope of this review. In order to put into practice, the definition of liquid biopsy, which is frequently mentioned in cancer researches, studies conducted at the level of metabolome in clinical applications are of great importance. In the near future, the information obtained as a result of untargeted metabolomic studies will be validated with targeted studies, and many new biomarkers that can be used for early diagnosis and process examination for different diseases at the metabolome level will find their place in clinical applications.
Keywords: Metabolomics; metabolome; systems biology; biochemical phenomena
- Watson JD, Crick FH. Molecular structure of nucleic acids; a structure for deoxyribose nucleic acid. Nature. 1953;25;171(4356):737-8. [Crossref] [PubMed]
- Bentley DR. The human genome project--an overview. Med Res Rev. 2000;20(3):189-96. [Crossref]
- Jones P. Bioinformatics in the post-genomic age. World Patent Information. 2001;23(4):349-54. [Crossref]
- Kitano H. Systems biology: a brief overview. Science. 2002;1;295(5560):1662-4. [Crossref] [PubMed]
- Griffiths WJ, Karu K, Hornshaw M, Woffendin G, Wang Y. Metabolomics and metabolite profiling: past heroes and future developments. Eur J Mass Spectrom (Chichester). 2007;13(1):45-50. [Crossref] [PubMed]
- Becker S, Kortz L, Helmschrodt C, Thiery J, Ceglarek U. LC-MS-based metabolomics in the clinical laboratory. J Chromatogr B Analyt Technol Biomed Life Sci. 2012;1;883:68-75. [Crossref] [PubMed]
- Griffiths WJ, Koal T, Wang Y, Kohl M, Enot DP, Deigner HP, et al. Targeted metabolomics for biomarker discovery. Angew Chem Int Ed Engl. 2010;26;49(32):5426-45. [Crossref] [PubMed]
- Venter JC. A part of the human genome sequence. Sicence. 2003;21;299(5610):1183-4. [Crossref] [PubMed]
- Xiao JF, Varghese RS, Zhou B, Nezami Ranjbar MR, Zhao Y, Tsai TH, et al. LC-MS based serum metabolomics for identification of hepatocellular carcinoma biomarkers in Egyptian cohort. J Proteome Res. 2012;7;11(12):5914-23. [Crossref] [PubMed] [PMC]
- Zhou B, Xiao JF, Tuli L, Ressom HW. LC-MS-based metabolomics. Mol Biosyst. 2012;8(2):470-81. [Crossref] [PubMed] [PMC]
- Strimbu K, Tavel JA. What are biomarkers?. Curr Opin HIV AIDS. 2010;5(6):463-6. [Crossref] [PubMed] [PMC]
- Miki Y, Swensen J, Shattuck-Eidens D, Futreal PA, Harshman K, Tavtigian S, et al. A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science. 1994;7;266(5182):66-71. [Crossref] [PubMed]
- Polascik TJ, Oesterling JE, Partin AW. Prostate specific antigen: a decade of discovery-what we have learned and where we are going. J Urol. 1999;162(2):293-306. [Crossref]
- Patti GJ, Yanes O, Siuzdak G. Innovation: Metabolomics: the apogee of the omic triology. Nat Rev Mol Cell Biol. 2012;22;13(4):263-9. [Crossref] [PubMed] [PMC]
- Başaran E, Aras S, Cansaran-Duman D. [General outlook and applications of genomics, proteomics and metabolomics]. Turkish Bulletin of Hygiene and Experimental Biology. 2010;67(2):85-96.
- Rieder MJ, Uetrecht J, Shear NH, Cannon M, Miller M, Spielberg SP, et al. Diagnosis of sulfonamide hypersensitivity reactions by in-vitro "rechallenge" with hydroxylamine metabolites. Ann Intern Med. 1989;15;110(4):286-9. [Crossref] [PubMed]
- van der Greef J, Smilde AK. Symbiosis of chemometrics and metabolomics: past, present, and future. J Chemometrics. 2005;19(5‐7):376-86. [Crossref]
- Institute UoTB, Research CF. [Individual Metabolic Patterns and Human Disease: An Exploratory Study Utilizing Predominantly Paper Chromatographic Methods, from the Biochemical Institute and the Dept. of Chemistry, the University of Texas, and the Clayton Foundation for Research, Austin, Issue 4. Austin: Austin University of Texas; 1951. p.205.
- Gates SC, Sweeley CC. Quantitative metabolic profiling based on gas chromatography. Clinical Chem. 1978;24(10):1663-73. [Crossref] [PubMed]
- Horning EC, Horning MG. Metabolic profiles: gas-phase methods for analysis of metabolites. Clin Chem. 1971;17(8):802-9. [Crossref] [PubMed] [PMC]
- Games DE, Alcock NJ, van der Greef J, Nyssen LM, Maarse H, Ten MC, et al. [Analysis of pepper and capsicum oleoresins by high-performance liquid chromatography--mass spectrometry and field desorption mass spectrometry]. Journal of Chromatography A. 1984;294:269-79. [Crossref]
- Bell JD, Brown JC, Sadler PJ. NMR studies of body fluids. NMR Biomed. 1989;2(5‐6):246-56. [Crossref] [PubMed]
- Plumb R, Castro‐Perez J, Granger J, Beattie I, Joncour K, Wright A, et al. Ultra‐performance liquid chromatography coupled to quadrupole‐orthogonal time‐of‐flight mass spectrometry. Rapid Commun Mass Spectrom. 2004;18(19):2331-7. [Crossref] [PubMed]
- Soga T, Heiger DN. Amino acid analysis by capillary electrophoresis electrospray ionization mass spectrometry. Anal Chem. 2000;15;72(6):1236-41. [Crossref] [PubMed]
- Fiehn O. Metabolomics-the link between genotypes and phenotypes. Plant Mol Biol. 2002;48(1-2):155-71. [Crossref] [PubMed]
- Wishart DS, Feunang YD, Marcu A, Guo AC, Liang K, Vázquez-Fresno R, et al. HMDB 4.0: the human metabolome database for 2018. Nucleic Acids Res. 2018;46(D1):D608-D17. [Crossref] [PubMed] [PMC]
- Gritti F, Guiochon G. The current revolution in column technology: how it began, where is it going?. J Chromatogr A. 2012;9;1228:2-19. [Crossref] [PubMed]
- Forsberg EM, Huan T, Rinehart D, Benton HP, Warth B, Hilmers B, et al. Data processing, multi-omic pathway mapping, and metabolite activity analysis using XCMS Online. Nature protocols, 2018;13(4), 633-51. [Crossref] [PubMed] [PMC]
- Tautenhahn R, Patti GJ, Rinehart D, Siuzdak G. XCMS online: a web-based platform to process untargeted metabolomic data. Anal Chem. 2012;5;84(11):5035-9. [Crossref] [PubMed] [PMC]
- Smith CA, Want EJ, O'Maille G, Abagyan R, Siuzdak G. XCMS: processing mass spectrometry data for metabolite profiling using nonlinear peak alignment, matching, and identification. Anal Chem. 2006;78(3):779-87. [Crossref] [PubMed]
- Çelebier M. [Software and database usage on metabolomic studies: using XCMS on LC-MS data analysis]. Archives Medical Review Journal. 2014;23(2):168-85. [Crossref]
- reek DJ, Jankevics A, Burgess KEV, Breitling R, Barrett MP. IDEOM: an Excel interface for analysis of LC-MS-based metabolomics data. Bioinformatics. 2012;1;28(7):1048-9. [Crossref] [PubMed]
- Katajamaa M, Miettinen J, Oresic M. MZmine: toolbox for processing and visualization of mass spectrometry based molecular profile data. Bioinformatics. 2006;1;22(5):634-6. [Crossref] [PubMed]
- Myers OD, Sumner SJ, Li S, Barnes S, Du X. Detailed investigation and comparison of the XCMS and MZmine 2 chromatogram construction and chromatographic peak detection methods for preprocessing mass spectrometry metabolomics data. Anal Chem. 2017;5;89(17):8689-95. [Crossref] [PubMed]
- Tautenhahn R, Boettcher C, Neumann S. Highly sensitive feature detection for high resolution LC/MS. BMC Bioinformatics. 2008; 9(504):1-16. [Crossref] [PubMed] [PMC]
- Nevedomskaya E, Derks R, Deelder AM, Mayboroda OA, Palmblad M. Alignment of capillary electrophoresis-mass spectrometry datasets using accurate mass information. Anal Bioanal Chem. 2009;395(8):2527-33. [Crossref] [PubMed]
- Nerlich B, Dingwall R, Clarke DD. The book of life: How the completion of the Human Genome Project was revealed to the public. Health. 2002;6(5):445-69. [Crossref]
- Slupsky CM, Steed H, Wells TH, Dabbs K, Schepansky A, Capstick V, et al. Urine metabolite analysis offers potential early diagnosis of ovarian and breast cancers. Clin Cancer Res. 2010;1;16(23):5835-41. [Crossref] [PubMed]
- Kim Y, Koo I, Jung BH, Chung BC, Lee D. Multivariate classification of urine metabolome profiles for breast cancer diagnosis. BMC Bioinformatics. 2010;16;11 Suppl 2(Suppl 2):S4. [Crossref] [PubMed] [PMC]
- Zhang F, Zhang Y, Zhao W, Deng K, Wang Z, Yang C, et al. Metabolomics for biomarker discovery in the diagnosis, prognosis, survival and recurrence of colorectal cancer: a systematic review. Oncotarget. 2017;23;8(21):35460-72. [Crossref] [PubMed] [PMC]
.: Process List