NO017.20190114.ClinPharmacolTher.Pharmacogenomics Knowledge for Personalized Medicine

原文链接：Pharmacogenomics Knowledge for Personalized Medicine

原文摘录：

1. The Pharmacogenomics Knowledgebase (PharmGKB) is a resource that collects, curates, and disseminates information about the impact of human genetic variation on drug responses.
2. Gene–drug–disease relationships are extracted from the literature using manual curation and natural language–processing techniques.
3. Variant annotations are the core component of the knowledge in PharmGKB.
4. Building on variant annotations, “clinical annotations” combine multiple-variant annotations into a single summary of the relevant variant–drug–phenotype association.
5. The level of risk for any given genotype is reported in a relative fashion as compared with other genotypes. For example, the AA genotype is associated with an increased risk of side effects as compared with the AG and GG genotypes—but not necessarily at an increased risk of side effects for patients on the drug in general, as this would depend on a detailed examination of the target-population allele frequencies and the populations on which the original US Food and Drug Administration approval is based.（这里是相对的，一种基因型相对于另外的基因型而言是这样的，并不代表对于药物本身而言就一定是这样的，这个还得结合其他的信息去看）
6. Thus, we report risk relative to other genotypes because the incidence of efficacy or adverse events for any given drug has usually not been quantified. Also, the distribution of genotypes for any given population is often not available.
7. Although many groups use HapMap frequencies to calculate population major alleles or typical genotypes, the HapMap populations are small and ethnically very specific.（有的研究组使用HapMap频率来计算人群的主要等位基因或者典型的基因型，但是HapMap人群是小样本的且是种族特异性的，不能普适套用）
8. Their frequencies do not necessarily represent larger population frequencies (nor were they meant to). Therefore, we do not report the risk of a particular drug response as compared with “normal” because normal is typically not well defined. We report the risk as compared with other possible genotypes.
9. The lack of evidence for an association can be important in a research setting, and so although variant annotations are created in these situations, they are not summarized as clinical annotations because they would have no clinical utility to a doctor, pharmacist, patient, or direct-to-consumer genotyping customer.（缺乏更多证据支持的关联对于研究是重要的，但是由于他们只是变异层面的注释而不是临床注释，因此对于医生、药剂师、患者或者直接面向消费者的基因分型客户都是没有太大用处的）
10. Pharmacogenetics and pharmacogenomics are at a critical juncture. As the field moves from the bench to clinical implementation, it requires a high-quality and reliable source of up-todate information about human genetic variation and its impact on drug response. The PharmGKB is the preeminent resource for enabling clinicians and translational researchers to implement pharmacogenomic knowledge in the context of personalized medicine.

The PharmGKB Knowledge Pyramid

备注

PharmGKB已经是精准医疗领域无法避开的一个重要资源了，国内外众多的精准医疗机构与公司的相关研发与产品都或多或少借鉴或整合了PharmGKB的数据，对其数据结构及处理方式有更深入的了解是非常必要的！