Department of Anesthesiology and Pain Medicine, Department of Genome Sciences, Mitochondrial and Metabolism Center, University of Washington, Seattle, Washington.
Department of Anesthesia Critical Care & Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts; Harvard Medical School, Boston Massachusetts.
Anesthesiology. 2024 Nov 1;141(5):997-1006. doi: 10.1097/ALN.0000000000005153.
Most of science involves making observations, forming hypotheses, and testing those hypotheses, to form valid conclusions. However, a distinct, longstanding, and very productive scientific approach does not follow this paradigm; rather, it begins with a screen through a random collection of drugs or genetic variations for a particular effect or phenotype. Subsequently, the identity of the drug or gene is determined, and only then are hypotheses formed and the more standard scientific method employed. This alternative approach is called forward screening and includes methods such as genetic mutant screens, small molecule screens, metabolomics, proteomics, and transcriptomics. This review explains the rational for forward screening approaches and uses examples of screens for mutants with altered anesthetic sensitivities and for novel anesthetics to illustrate the methods and impact of the approach. Forward screening approaches are becoming even more powerful with advances in bioinformatics aided by artificial intelligence.
大多数科学研究包括观察、形成假设和检验假设，以形成有效的结论。然而，有一种独特的、长期存在的、非常有成效的科学方法并不遵循这一模式；相反，它从对特定效应或表型的随机药物或遗传变异的筛选开始。随后，确定药物或基因的身份，然后才形成假设并采用更标准的科学方法。这种替代方法称为正向筛选，包括遗传突变体筛选、小分子筛选、代谢组学、蛋白质组学和转录组学等方法。这篇综述解释了正向筛选方法的合理性，并以改变麻醉敏感性的突变体和新型麻醉剂的筛选为例，说明了这种方法的方法和影响。随着人工智能辅助的生物信息学的进步，正向筛选方法变得更加强大。
