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3 数据分析
代谢组学得到的是大量的、多维的信息,为了充分抽提数据中的潜在信息,对数据的分析需要应用一系列的化学计量学方法。在代谢组学的研究中,数据分析过程中应用的技术集中在模式识别技术上,模式识别技术主要有主成分分析(principalcomponents analysis,PCA)、非线形映射(nonlinearmapp ing,NLM)、簇类分析(hierarchical cluster analysis,HCA)等非监督(unsupervised)研究方法和SMICA(soft independentmodeling of class analogy)、PLS-DA(PLS-discrmi inant analysis),ANN(artificial neural newtork)等监督(supervised)研究方法。PCA将分散于一组变量上的信息集中于几个综合指标上,如糖代谢、脂质代谢、氨基酸代谢等,利用主成分(PC)描述机体代谢的变化情况,能够简化数据并易化分析[19]。
4 代谢组学技术在微生物领域的应用
4.1 对微生物进行分类及筛选突变体
随着分子生物学的迅速发展,联合基因型与表型对微生物进行分类已成为一种趋势。代谢组学技术的发展使代谢谱分析方法(metabolic profiling)逐渐成为一种快速、高通量、全面的表型分类方法,通过对代谢组的分析对细菌进行分类。Bu ndy等[20]通过代谢谱分析成功地区分开临床病理来源以及实验室来源的不同杆菌(bacillus cereus)。在未发生明显表型变化的突变体内,突变基因有可能导致某些代谢途径发生变化,通过代谢组分析可以发现该突变体并研究相应基因的功能[21]。
4.2 在代谢工程领域的应用
U.Nasution[22]利用代谢组学手段通过动态检测恒化培养的Penicillium chrysogenum的糖酵解、三羧酸循环过程,认为通过修饰其新陈代谢能得到高产量的药物,这些高产量的药物与细胞内初级代谢有关。Dalluge等[23]利用LC-MS-MS方法监控发酵过程中的氨基酸谱纹,实现对整个发酵系统的牙体牙髓牙周病学杂志(Chin J Conserv Dent)2010,20(1)53高通量快速监控。Bernd Kammerera等[24]用反相高效液相色谱、电喷射质谱、三联四极质谱在Strep tomyces species中寻找未知的媒介物、次级代谢产物,同时用MS-MS检测极低浓度的氨基香豆素抗生素,检测到一种新的化合物香豆霉素A1和10种不同的媒介物(有3种是新发现的),从而探索Streptomyces spespecies生物合成和发现新的潜在的抗生素。
5 代谢组学在口腔领域中的应用
随着代谢组学技术的发展,该方法也逐渐应用于口腔领域。李淼等[25]用代谢组学技术鉴定区分了两种口腔常见致龋菌变形链球菌和黏性放线菌,认为代谢组学技术有望应用于口腔细菌的快速鉴定。Yan等[26]用代谢组学的方法对口腔鳞状细胞癌、口腔扁平苔藓和口腔白斑进行了诊断,提示其作为一种有效的方法有望用于对口腔癌变及癌前病变进行筛选。
代谢组学作为功能基因组学的重要组成部分,直接反应了生物体的生理状态,虽然其尚处于研究应用的初级阶段,但通过代谢组学的研究极有可能去发现新的生化途径并解释正常的或病理的功能,如在口腔领域通过研究口腔致龋菌及其突变株的糖酵解途径去分析不同的致病机理。代谢组学的成功发展不仅需要能快速检测、鉴别和定量复杂代谢产物的技术,还需要微生物学家、分析化学家、统计学家、信息学家的共同合作。相信随着代谢组学的发展一定能快速推进生物医学领域的飞速发展。
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