National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Genome Res. 2013 Jul;23(7):1051-3. doi: 10.1101/gr.157826.113.
Genomics has profoundly changed biology by scaling data acquisition, which has provided researchers with the opportunity to interrogate biology in novel and creative ways. No longer constrained by low-throughput assays, researchers have developed hypothesis-generating approaches to understand the molecular basis of nature-both normal and pathological. The paradigm of hypothesis-generating research does not replace or undermine hypothesis-testing modes of research; instead, it complements them and has facilitated discoveries that may not have been possible with hypothesis-testing research. The hypothesis-generating mode of research has been primarily practiced in basic science but has recently been extended to clinical-translational work as well. Just as in basic science, this approach to research can facilitate insights into human health and disease mechanisms and provide the crucially needed data set of the full spectrum of genotype-phenotype correlations. Finally, the paradigm of hypothesis-generating research is conceptually similar to the underpinning of predictive genomic medicine, which has the potential to shift medicine from a primarily population- or cohort-based activity to one that instead uses individual susceptibility, prognostic, and pharmacogenetic profiles to maximize the efficacy and minimize the iatrogenic effects of medical interventions.
基因组学通过扩大数据采集规模极大地改变了生物学，为研究人员提供了以新颖和创造性的方式探究生物学的机会。研究人员不再受限于低通量检测，已经开发出了生成假说的方法，以理解自然的分子基础——无论是正常还是病理的。生成假说的研究范式并没有取代或破坏假说检验的研究模式；相反，它补充了这些模式，并促进了那些通过假说检验研究可能无法实现的发现。生成假说的研究模式主要在基础科学中实践，但最近也扩展到了临床转化工作中。就像在基础科学中一样，这种研究方法可以促进对人类健康和疾病机制的深入了解，并提供全基因组型-表型相关性的急需数据集。最后，生成假说的研究范式在概念上类似于预测性基因组医学的基础，后者有可能将医学从主要基于人群或队列的活动转变为利用个体易感性、预后和药物遗传学特征来最大限度地提高医疗干预的疗效并最小化医源性影响的活动。
