Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK.
Queen Square Brain Bank for Neurological Disorders, UCL Queen Square Institute of Neurology, London, UK.
Alzheimers Dement. 2023 Dec;19(12):5905-5921. doi: 10.1002/alz.13427. Epub 2023 Aug 22.
Genetics and omics studies of Alzheimer's disease and other dementia subtypes enhance our understanding of underlying mechanisms and pathways that can be targeted. We identified key remaining challenges: First, can we enhance genetic studies to address missing heritability? Can we identify reproducible omics signatures that differentiate between dementia subtypes? Can high-dimensional omics data identify improved biomarkers? How can genetics inform our understanding of causal status of dementia risk factors? And which biological processes are altered by dementia-related genetic variation? Artificial intelligence (AI) and machine learning approaches give us powerful new tools in helping us to tackle these challenges, and we review possible solutions and examples of best practice. However, their limitations also need to be considered, as well as the need for coordinated multidisciplinary research and diverse deeply phenotyped cohorts. Ultimately AI approaches improve our ability to interrogate genetics and omics data for precision dementia medicine. HIGHLIGHTS: We have identified five key challenges in dementia genetics and omics studies. AI can enable detection of undiscovered patterns in dementia genetics and omics data. Enhanced and more diverse genetics and omics datasets are still needed. Multidisciplinary collaborative efforts using AI can boost dementia research.
阿尔茨海默病和其他痴呆亚型的遗传学和组学研究增强了我们对潜在机制和可靶向途径的理解。我们确定了关键的遗留挑战:首先,我们能否增强遗传研究以解决遗传缺失问题?我们能否确定可区分痴呆亚型的可重复组学特征?高维组学数据能否识别出改进的生物标志物?遗传学如何帮助我们了解痴呆风险因素的因果地位?哪些生物过程会被与痴呆相关的遗传变异改变?人工智能 (AI) 和机器学习方法为我们提供了强大的新工具,帮助我们应对这些挑战,我们将回顾可能的解决方案和最佳实践示例。然而,也需要考虑到它们的局限性,以及协调多学科研究和多样化的深度表型队列的必要性。最终,人工智能方法提高了我们通过精准痴呆医学对遗传学和组学数据进行探究的能力。重点:我们已经确定了痴呆遗传学和组学研究中的五个关键挑战。AI 可以帮助发现痴呆遗传学和组学数据中的未知模式。需要增强和更多样化的遗传学和组学数据集。使用 AI 的多学科合作可以促进痴呆研究。