Understanding links between genetics and biology to advance drug discovery

写的:

Results from the largest proteogenomics 研究 to date could transform how we, 和其他人方法药物发现. 在分析了50多个,来自英国生物银行的1000个人类外显子组, we uncovered links between rare protein-coding genetic variants and nearly 3,000血浆蛋白. 这一发现, which we are making available to the global scientific community 在AZPheWAS.com, are uncovering previously unknown insights into disease biology that can help accelerate the identification of new therapeutic targets and biomarkers.

正如澳门葡京赌博游戏最近的合著者所说 自然 研究 澳门葡京赌博游戏R的执行副总裁&D(退休), Mene Pangalos: “A selective high-quality molecule will never become a medicine if it is modulating the wrong target.“这就是为什么选择 正确的目标 remains the most important decision we make in the drug discovery process.

Drug candidates that target genes or 蛋白质 that are clearly linked to human disease are much more likely to demonstrate clinically meaningful outcomes and therefore, 是否更有可能被批准造福患者. 蛋白质是生物学的功能单位, 在结构中发挥关键作用, 监管, 能源监管等. 因为它们在身体中扮演着重要的角色, mutations or variations in genes that affect protein function or levels of expression can greatly affect biological processes and human health.

Delving deeper: Combining genomics with proteomics to advance drug discovery

In a breakthrough 研究 conducted by our Centre for Genomic Research (CGR) research team, 澳门葡京赌博游戏分析了50多个,000 human exomes in the UK Biobank dataset to uncover the contribution of rare protein-coding genetic variants on nearly 3,000血浆蛋白.¹ Plasma 蛋白质 circulate in the blood, originating from multiple organs and cell types. Therefore, they can provide a unique snapshot of the current state of health or disease.

Several previous studies have shown thousands of associations between common or non-protein coding genetic variants and plasma protein abundance, 然而, the effect of rare protein-coding variants on plasma 蛋白质 has not been studied at this scale, 直到现在.

与普通基因变异相比, rare variants offer stronger evidence and unique insights into the direct relationships between genes, 蛋白质, 以及它们在疾病中的作用.  通过关注这些变体, 澳门葡京赌博游戏确定了除以4,400 significant ‘protein quantitative trait loci’ – gene variants associated with protein function essential to health. 超过四分之三的地方从未被发现过, even in previous studies that used a similar UK Biobank cohort.²

The findings from this research allow us to better understand the impact that certain genes and 蛋白质 have on disease. 现在, 澳门葡京赌博游戏可以将这些见解应用于药物发现和开发, 为疾病机制提供新的见解, 可能的脱靶药物效应, 新目标发现, 和更多的.

例如, 使用这个分析, we discovered previously undescribed plasma biomarkers associated with a rare variant in the HSD17B13 gene that is implicated in protection against chronic liver diseases including 非酒精性脂肪性肝炎(NASH).¹ Having a better understanding of the biological effects of this variant could allow us to better 发展有针对性的精准医学疗法 来改善NASH患者的预后.

这一发现, along with the thousands of others that exist within this dataset have the potential to be transformational to how we, 以及更广泛的科学界方法药物发现. 最终, 通过改进目标识别, we can move towards matching patients with the treatments that are most likely to help.

通过合作向世界开放澳门葡京赌博游戏的科学

开放的科学, 承诺分享科学信息, 是科学研究进步的基础吗. That’s why we have made all summary statistics from this research available on AZPheWAS.com 供全球的学者和研究人员使用. 一旦在网站上, 研究人员可以通过基因进行Search, variant or phenotype to discover genetically anchored disease-protein associations to gain novel insights and a deeper understanding of the biology of common diseases.

Our main purpose is to push the boundaries of science to deliver life-changing medicines. 澳门葡京赌博游戏知道，澳门葡京赌博游戏无法独自完成这项任务, so we have established an open and collaborative way of working to promote greater research efficiency while reducing unnecessary duplication in genomics research.

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