Institute for Systems Biology, Seattle, WA, USA.
Biotechnol J. 2012 Aug;7(8):946-57. doi: 10.1002/biot.201100305. Epub 2012 Apr 23.
In the past 15 years, new "omics" technologies have made it possible to obtain high-resolution molecular snapshots of organisms, tissues, and even individual cells at various disease states and experimental conditions. It is hoped that these developments will usher in a new era of personalized medicine in which an individual's molecular measurements are used to diagnose disease, guide therapy, and perform other tasks more accurately and effectively than is possible using standard approaches. There now exists a vast literature of reported "molecular signatures". However, despite some notable exceptions, many of these signatures have suffered from limited reproducibility in independent datasets, insufficient sensitivity or specificity to meet clinical needs, or other challenges. In this paper, we discuss the process of molecular signature discovery on the basis of omics data. In particular, we highlight potential pitfalls in the discovery process, as well as strategies that can be used to increase the odds of successful discovery. Despite the difficulties that have plagued the field of molecular signature discovery, we remain optimistic about the potential to harness the vast amounts of available omics data in order to substantially impact clinical practice.
在过去的 15 年中，新的“组学”技术使得在各种疾病状态和实验条件下对生物体、组织甚至单个细胞进行高分辨率分子快照成为可能。人们希望这些发展将开创个性化医疗的新时代，在这个时代，个体的分子测量结果将被用于更准确、更有效地诊断疾病、指导治疗以及执行其他任务，而这是使用标准方法无法实现的。现在已经有大量报道的“分子特征”文献。然而，尽管有一些值得注意的例外，许多这些特征在独立数据集的再现性上受到限制，其灵敏度或特异性不足以满足临床需求，或存在其他挑战。在本文中，我们根据组学数据讨论了分子特征发现的过程。特别是，我们强调了发现过程中的潜在陷阱，以及可以用来增加成功发现的可能性的策略。尽管分子特征发现领域存在困难，但我们仍然对利用大量可用的组学数据来对临床实践产生重大影响持乐观态度。
