代谢指纹图谱分析技术及数据处理方法研究进展Advance of studies on metabolic fingerprinting analytical techniques and data processing methods
高健;杨更亮;杨洪军;许海玉;李韶菁;
GAO Jian1,YANG Geng-liang1,YANG Hong-jun2,XU Hai-yu2,LI Shao-jing2(1.College of Pharmaceutical Science,Hebei University,Baoding 071002,China; 2.Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing 100700,China)
摘要(Abstract):
代谢组学是继基因组学、转录组学和蛋白质组学之后的一门新兴学科,旨在系统研究机体代谢产物的变化规律,揭示机体生命活动代谢本质,尤其在现代药理研究中发挥重要作用。代谢指纹图谱分析(metabolic finger printing analysis)是对所有代谢物整体进行高通量的代谢分析的方法,研究药物本身、机体本身及药物引起的机体内源性代谢物的变化,找出与之相关的生物标志物,因此可以更直接地反映体内状态的动态变化,阐明药物及疾病作用机制。该文综述了目前用于代谢指纹图谱的一些新的分析手段和数据处理方法,阐述其优缺点,并展望了其与中医药研究相结合,有望促进中医药复杂理论体系研究新方法和新途径产生的发展前景。
Metabolomics is an emerging discipline subsequent to genomics,transcriptomics and proteomics,aiming for systematically studying the regularity of changes in metabolite to revealing organism′s nature of movement and metabolism.It is especially important in modern pharmacological studies.Metabolic fingerprinting analysis is a method for metabolic analysis on high throughput of all metabolites,studying changes in drugs,organisms and endogenic metabolites caused by drugs and finding out related biomarkers to reflect dynamic changes inside organisms more directly and explain the mechanism of drugs and their effects on diseases.This essay summarizes some new metabolic fingerprint analytical methods and data processing methods used for metabolic fingerprint,elaborates their advantages and disadvantages and looks ahead to their combination with studies on traditional Chinese medicines,providing room for the development of new methods and new approaches for studies on complexity theory system of traditional Chinese medicines.
关键词(KeyWords):
代谢组学;代谢指纹图谱;生物标记物
metabolomics;metabolic fingerprinting analysis;biomarker
基金项目(Foundation): 国家自然科学基金项目(30901976);; 中国中医科学院第二批自主选题项目(Z02076,Z02063)
作者(Author):
高健;杨更亮;杨洪军;许海玉;李韶菁;
GAO Jian1,YANG Geng-liang1,YANG Hong-jun2,XU Hai-yu2,LI Shao-jing2(1.College of Pharmaceutical Science,Hebei University,Baoding 071002,China; 2.Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing 100700,China)
Email:
DOI:
参考文献(References):
- [1]Sumner L W,Mendes P,Dixon R A.Plant metabolomics:large-scale phytochemistry in the functional genomics era[J].Phyto-chemistry,2003,62(6):817.
- [2]Vallejo M,Angulo S,Garcia-Martinez D A,et al.New perspectiveof diabetes response to an antioxidant treatment through metabolicfingerprinting of urine by capillary electrophoresis[J].J Chroma-togr A,2008,1187:267.
- [3]Lindon J C,Keun H C,Ebbels T M D,et al.The consortium formetabonomic toxicology(COMET):aims,activities andachievements[J].Pharmacogenomics,2005,6(7):69l.
- [4]Keun H C.Metabonomic modeling of drug toxicity[J].Pharmacol&Therapeut,2006,109(1/2):92.
- [5]Rochfort S.Metabolomics reviewed:a new″omics″platform tech-nology for systems biology and implications for natural products re-search[J]J Nat Prod,2005,68(12):1813.
- [6]Chen M J,Zhao L P,Jia W J.Metabolomic study on the biochemi-cal profiles of a hydrocortisone induced animal model[J].Pro-teome Res,2005,4(6):2391.
- [7]Catchpole G S,Beckmann M,Enot D P,et al.Hierarchicalmetabolomics demonstrates substantial compositional similarity be-tween genetically modified and conventional potato crops[J].ProcNatl Acad Sci USA,2005,102(40):14458.
- [8]Chen M J,Su M M,Zhao L P,et al.Metabonomic study of aristolo-chic acid-induced nephrotoxicity in rats[J].Proteome Res,2006,5(4):995.
- [9]Castle A L,Carver M R,Mendriek D L.Toxicogenomics:a newrevolution in drug safety[J].Drug Discov[J].Today,2002,7(13):728.
- [10]Clayton T A,Lindon J C,Cloaree O,et al.Pharmacometabonomicphenotyping and personalized drug treatment[J].Nature,2006,440(7087):1073.
- [11]Fiehn O,Kloska S,Altmann T.Integrated studies on plant biologyruing multiparallel techniques[J].Curt Opin Biotechnol,200l,12:82.
- [12]Allen J,Daveyh M,Broadhurst D,et a1.Discrimination of modesof action of antifungal substances by use of metabolic footprinting[J].Nature Biotechnol,2003,21(6):692.
- [13]Boulesteix A,Strimmer K.Partial least squares:a versatile tool forthe analysis of high-dimensional genomic data[J].Brief Bioin-form,2007(8):32.
- [14]Scholkopf B,Tsuda K,Vert J P.Kernel Methods in computationalbiology[M].Cambridge:MIT Press,2004:511.
- [15]Shawe-Taylor J,Cristianini N.Kernel methods for pattern analysis[M].Cambridge:Cambridge University Press,2004:5111.
- [16]Soga T K,akazu Y J,Robert M,et al.Qualitative and quantitativeanalysis of amino acids by capillary electrophoresis electrosprayionizationt and emmass spectrometry[J].Electrophoresis,2004,25(13):1964.
- [17]Reynolds W F,Enriquez R G.Choosing the best pulse sequencesacquisition parameters postacquisition processing strategies andprobes for natural product structure elucidation by NMR spectros-copy[J].J Nat Prod,2002,65(2):221.
- [18]Xia J G,Bjorndahl T C,Tang P,et al.MetaboMiner-semi-automa-ted identification of metabolites from 2D NMR spectra of complexbiofluids[J].BMC Bioinformat,2008,9:507.
- [19]Cloarec O,Dumas M,Craig A,et al.Statistical total correlationspectroscopy:an exploratory approach for latent biomarker identi-fication from metabolic1H-NMR data sets[J].Anal Chem,2005,77(5):1282.
- [20]Crockford D J,Holmes E,Lindon J C,et al.Statistical heterospec-troscopy,an approach to the integrated analysis of NMR and UP-LC-MS data sets:application in metabonomic toxicology studies[J].Anal Chem,2006,78(2):363.
- [21]Griffin J L,Cemal C K,Pook M A.Defining a metabolic phenotypein the brain of a transgenic mouse model of spinocerebellar ataxia[J].Physiol Gen,2004,16(3):334.
- [22]Yin P Y,Zhao X J,Li Q R,et al.Metabonomicsstudy of intestinalfistulas based on ultraperformance liquid chromatography coupledwith Q-TOF mass spectrometry(UPLC/Q-TOF/MS)[J].Pro-teome Res,2006,5(9):2135.
- [23]Daykinc A,Corcoran O,Hansens H,et al.Application of directlycoupled HPLC-NMR to separation and characterization of lipopro-teins from human serum[J].Anal Chem,2001,73(6):1084.
- [24]Lindon J C,Holmes E,Nicholson J K.So what is the deal withmetabonomics[J].Anal Chem,2003,75(17):384A.
- [25]Trygg J,Wold S.Orthogonal projections to latent structures(O-PLS)[J].J Chemometrics,2002,16(3):119.
- [26]Trygg J.O-PLS for qualitative and quantitative analysis in multiva-riate calibration[J].Joumal of Chemometrics,2002,16(6):283.
- [27]Fiehn O.Combining genomics,metabolome analysis,and biochem-ical modelling to understand metabolic networks[J].ComparativeFunctional Genomics,2001,2(3):155.
- [28]Woldsmh,Woldh.The multivariate calibration method in chemistrysolved by the PLS method in proceeding on the conference on ma-trix pencils:lecture notes in mathematics[C].Heidelberg:Springer Verlag,1983:286.
- [29]Bijlsmas,Bobeldijki,Verheijer,et al.Large-scale human metabolo-mics studies:a strategy for data(pre-)processing and validation[J].Anal Chem,2006,8(2):567.
- [30]Nguyendv,Rockedm.Tumor classification by partial leasts quaresusing microarray gene expression data[J].Bioinformatics,2002,8(1):39.
- [31]Wang C,Kong H,Guan Y,et al.Plasma phospholipid metabolicprofiling and biomarkers of type 2 diabetes mellitus based on highperformance liquid chromatography/electrospray mass spectrome-try and multivariate statistical analysis[J].Anal Chem,2005,7(13):4108.
- [32]Wang Y,Holmes E,Nicholson J K,et al.Metabonomic investiga-tions in mice infected with Schist soma man son:an approach forbiomarker identification[J].Proc Natl Acad Sci USA,2004,34(1):12676.
- [33]许海玉,唐仕欢,陈建新,等.基于代谢组学的中药“组效关系”研究思路与策略[J].世界科学技术——中医药现代化,2011,13(1):30.
- 高健
- 杨更亮
- 杨洪军
- 许海玉
- 李韶菁
GAO Jian1- YANG Geng-liang1
- YANG Hong-jun2
- XU Hai-yu2
- LI Shao-jing2(1.College of Pharmaceutical Science
- Hebei University
- Baoding 071002
- China
- 2.Institute of Chinese Materia Medica
- China Academy of Chinese Medical Sciences
- Beijing 100700
- China)
- 高健
- 杨更亮
- 杨洪军
- 许海玉
- 李韶菁
GAO Jian1- YANG Geng-liang1
- YANG Hong-jun2
- XU Hai-yu2
- LI Shao-jing2(1.College of Pharmaceutical Science
- Hebei University
- Baoding 071002
- China
- 2.Institute of Chinese Materia Medica
- China Academy of Chinese Medical Sciences
- Beijing 100700
- China)