Using AI to investigate and modulate gene function in patient populations and biobanks

药物靶标识别和验证是药物发现的关键基础，已被证明广泛地受到遗传数据的影响。这个MSD合作博士将专注于使用AI来解释破坏蛋白质编码基因功能的遗传变化。通过将变异与表型联系起来，可以识别人类基因敲除的良性和破坏性影响，并对药物发现产生直接影响，包括识别更安全的靶标或药物重新定位机会，或早期识别药物发现的潜在风险。该项目将从一些将遗传变异与人类表型和疾病风险联系起来的全球合作项目中获得信息，特别关注来自基因与健康的基因分型和外显子组数据，这是一项针对生活在英国的南亚近亲个体的大规模研究。基因与健康（https：//www.genesandhealth.org/）是一个独特的研究项目，与东伦敦、布拉德福德和曼彻斯特的南亚社区合作，这些社区是英国心脏病、糖尿病和健康状况不佳的高发地区。独特的是，这项研究涉及整个社区，将初级和二级保健联系起来。这为探索广泛的表型提供了机会，包括健康和健康老龄化的广泛措施，最终导致改善英国和全球社区健康的新方法。

Drug target identification and validation is a critical foundation in drug discovery that has been shown to be extensively informed by genetic data. This MSD collaborative PhD will focus on using AI for the interpretation of genetic changes that disrupt the function of protein-coding genes. By linking variants to phenotype it is possible to identify both benign and damaging impacts from human knockouts with immediate implications for drug discovery, including the identification of safer targets or drug repositioning opportunities, or the early identification of potential risks for drug discovery. The project will feed from a number of global collaborative projects linking genetic variation to human phenotypes and disease risk, with a particular focus on genotyping and exome data from Genes and Health, a large-scale study in consanguineous South Asian individuals living in the UK. Genes and Health (https://www.genesandhealth.org/) is a unique research programme working with the South Asian communities in East London, Bradford and Manchester, which have some of the highest rates of heart disease, diabetes, and poor health in the UK. Uniquely the study involves the whole community, linking across primary and secondary care. This presents an opportunity to explore a wide range of phenotypes, including broad measures of health and healthy aging, ultimately leading to new ways of improving health for communities in the UK and worldwide.