Conrads Thomas P, Hood Brian L, Veenstra Timothy D
National Cancer Institute, Frederick, MD 21702, USA.
Biotechniques. 2006 Jun;40(6):799-805. doi: 10.2144/000112196.
There is an often unspoken truth behind the course of scientific investigation that involves not what is necessarily academically worthy of study, but rather what is scientifically worthy in the eyes of funding agencies. The perception of worthy research is, as cost is driven in the simplest sense in economics, often driven by demand. Presently, the demand for novel diagnostic and therapeutic protein biomarkers that possess high sensitivity and specificity is placing major impact on the field of proteomics. The focal discovery technology that is being relied on is mass spectrometry (MS), whereas the challenge of biomarker discovery often lies not in the application of MS but in the underlying proteome sampling and bioinformatic processing strategies. Although biomarker discovery research has been historically technology-driven, it is clear from the meager success in generating validated biomarkers that increasing attention must be placed at the pre-analytic stage, such as sample retrieval and preparation. As diseases vary, so do the combinations of sampling and sample analyses necessary to discover novel biomarkers. In this review, we highlight different strategies used toward biomarker discovery and discuss them in terms of their reliance on technology and methodology.
在科学研究过程背后，存在着一个常常未被言明的事实，即这一过程所涉及的并非必然是学术上值得研究的内容，而是在资助机构眼中具有科学价值的东西。正如在经济学中成本在最基本意义上是由需求驱动的一样，对有价值研究的认知往往也是由需求驱动的。目前，对具有高灵敏度和特异性的新型诊断和治疗性蛋白质生物标志物的需求正在对蛋白质组学领域产生重大影响。所依赖的核心发现技术是质谱（MS），而生物标志物发现的挑战往往不在于质谱的应用，而在于基础蛋白质组采样和生物信息学处理策略。尽管生物标志物发现研究历来是技术驱动的，但从生成经过验证的生物标志物方面取得的微薄成功可以明显看出，必须更加关注分析前阶段，如样本采集和制备。由于疾病各不相同，发现新型生物标志物所需的采样和样本分析组合也各不相同。在这篇综述中，我们重点介绍了用于生物标志物发现的不同策略，并根据它们对技术和方法的依赖程度进行了讨论。
