drug targets | genetic | 遗传 | 药物靶点



think big




对比和关联(comparison and association)【DEG,GWAS,影像学,都是为了找疾病关联的signal】








先把这个plos genetics读一下,再去读最开始的NG,了解一些最基本的概念。

All authors are employees of AbbVie.



drug targets with human genetic evidence of disease association are twice as likely to lead to approved drugs



  human genetics evidence approved drug
gene1 1 1
gene2 1 1
gene3 0 0
gene4 1 0






causal genes are clear (Mendelian traits and GWAS associations linked to coding variants),单基因病以及编码区的variant都属于比较明确的causal gene。

historical drug approvals,类似炒股预测, 能不能用历史数据来预测未来的药物成功率

assess which types of genetic evidence are most likely to be useful in guiding drug discovery,更细一点,探究哪种遗传证据更高效

We find genetic evidence from severe genetic disorders and from genetic variants that alter protein sequence is more strongly associated with historical approvals.


offer statistical approaches for prioritizing new drug candidates based on whether their mechanisms are supported by human genetic evidence. 提供了统计模型来预测新药的成功率




only 5-10% of candidate NMEs in early-stage clinical trials are eventually approved

increasing the fraction of NMEs in development with genetic support from the current value of 15% to 50% is predicted to decrease the direct R&D cost per launched drug by 22 ± 13%

NG paper说,增加genetic support,从现在的15%增加到50%,可以减少22 ± 13%的研发支出。

leveraging genetic data to predict the success of a new drug targets【可以看看相关的研究】

genetic support也分种类,unambiguous causal genes肯定100%能让drug得到approve,那其他的genetic evidence呢?

If the association between human genetic evidence and approved drugs is genuine and continues to hold for present-day drug development, we expect better variant to gene mapping methods and more sophisticated predictive approaches will further improve our ability to prioritize drug targets. 这不就是我们正在做的工作吗,variant to gene mapping,gene prioritization


Nelson et al. [3] estimated a twofold increase in approval probability for Phase I drug targets with genetic evidence using drug pipeline data from Informa Pharmaprojects along with genetic data from a variety of sources, all obtained in 2013.

Phase I drug targets with genetic evidence有2倍的通过率。用的是历史数据,所以当时无法重复。





A Mendelian trait is one that is controlled by a single locus in an inheritance pattern. 

New molecular entities (NMEs), as defined by the FDA, are new drug products containing as their active ingredient a chemical substance marketed for the first time in the United States.

Gain-of-function Mutation. A type of mutation in which the altered gene product possesses a new molecular function or a new pattern of gene expression. Gain-of-function mutations are almost always Dominant or Semidominant.

pharmaceutical industry

quantity and quality



Are drug targets with genetic support twice as likely to be approved? Revised estimates of the impact of genetic support for drug mechanisms on the probability of drug approval

Pharmaprojects: track pharma R&D  - Informa公司主导的一个大型项目

genetic-evidence-approval - GitHub


The support of human genetic evidence for approved drug indications - NG - 2015

Validating therapeutic targets through human genetics - review - 2013


posted @ 2021-04-01 15:45  Life·Intelligence  阅读(16)  评论(0编辑  收藏