Doping Control Laboratory, AIT Seibersdorf Laboratories, A-2444 Seibersdorf, Austria.
Forensic Sci Int. 2011 Dec 10;213(1-3):20-34. doi: 10.1016/j.forsciint.2011.07.031. Epub 2011 Aug 20.
During the past decade OMICS-methods not only continued to have their impact on research strategies in life sciences and in particular molecular biology, but also started to be used for anti-doping control purposes. Research activities were mainly reasoned by the fact that several substances and methods, which were prohibited by the World Anti-Doping Agency (WADA), were or still are difficult to detect by direct methods. Transcriptomics, proteomics, and metabolomics in theory offer ideal platforms for the discovery of biomarkers for the indirect detection of the abuse of these substances and methods. Traditionally, the main focus of transcriptomics and proteomics projects has been on the prolonged detection of the misuse of human growth hormone (hGH), recombinant erythropoietin (rhEpo), and autologous blood transfusion. An additional benefit of the indirect or marker approach would also be that similarly acting substances might then be detected by a single method, without being forced to develop new direct detection methods for new but comparable prohibited substances (as has been the case, e.g. for the various forms of Epo analogs and biosimilars). While several non-OMICS-derived parameters for the indirect detection of doping are currently in use, for example the blood parameters of the hematological module of the athlete's biological passport, the outcome of most non-targeted OMICS-projects led to no direct application in routine doping control so far. The main reason is the inherent complexity of human transcriptomes, proteomes, and metabolomes and their inter-individual variability. The article reviews previous and recent research projects and their results and discusses future strategies for a more efficient application of OMICS-methods in doping control.
在过去的十年中，OMICS 方法不仅继续对生命科学，特别是分子生物学的研究策略产生影响，而且开始用于反兴奋剂控制目的。研究活动主要是基于这样一个事实，即世界反兴奋剂机构（WADA）禁止的几种物质和方法，或者仍然难以通过直接方法检测到。转录组学、蛋白质组学和代谢组学理论上为发现这些物质和方法滥用的生物标志物提供了间接检测的理想平台。传统上，转录组学和蛋白质组学项目的主要重点一直是延长对人类生长激素（hGH）、重组促红细胞生成素（rhEpo）和自体输血滥用的检测。间接或标志物方法的另一个好处是，类似作用的物质也可以通过单一方法检测到，而不必为新的但可比的禁用物质开发新的直接检测方法（例如，各种形式的 Epo 类似物和生物仿制药）。虽然目前有几种非 OMICS 衍生的参数可用于间接检测兴奋剂，例如运动员生物护照的血液学模块的血液参数，但迄今为止，大多数非靶向 OMICS 项目的结果并没有直接应用于常规兴奋剂控制。主要原因是人类转录组、蛋白质组和代谢组及其个体间变异性的固有复杂性。本文回顾了以前和最近的研究项目及其结果，并讨论了未来更有效地将 OMICS 方法应用于兴奋剂控制的策略。
