Department of Computer Science.
Molecular and Cell Biology Program.
Curr Opin HIV AIDS. 2019 Jul;14(4):253-264. doi: 10.1097/COH.0000000000000558.
Experimental and analytical advances have enabled systematic, high-resolution studies of humoral immune responses, and are beginning to define mechanisms of immunity to HIV.
High-throughput, information-rich experimental and analytical methods, whether genomic, proteomic, or transcriptomic, have firmly established their value across a diversity of fields. Consideration of these tools as trawlers in 'fishing expeditions' has faded as 'data-driven discovery' has come to be valued as an irreplaceable means to develop fundamental understanding of biological systems. Collectively, studies of HIV-1 infection and vaccination including functional, biophysical, and biochemical humoral profiling approaches have provided insights into the phenotypic characteristics of individual and pools of antibodies. Relating these measures to clinical status, protection/efficacy outcomes, and cellular profiling data using machine learning has offered the possibility of identifying unanticipated mechanisms of action and gaining insights into fundamental immunological processes that might otherwise be difficult to decipher.
Recent evidence establishes that systematic data collection and application of machine learning approaches can identify humoral immune correlates that are generalizable across distinct HIV-1 immunogens and vaccine regimens and translatable between model organisms and the clinic. These outcomes provide a strong rationale supporting the utility and further expansion of these approaches both in support of vaccine development and more broadly in defining mechanisms of immunity.
综述目的:实验和分析方法的进步使我们能够对体液免疫反应进行系统、高分辨率的研究,并开始定义针对 HIV 的免疫机制。
最新发现:无论是基因组、蛋白质组还是转录组,高通量、信息丰富的实验和分析方法都已经在多个领域确立了其价值。这些工具曾被视为“捞针的渔网”,而“数据驱动的发现”现在被视为理解生物系统的基本原理的不可或缺的手段,因此,人们对这些工具的重视程度已经降低。对 HIV-1 感染和疫苗接种的研究,包括功能性、生物物理和生化体液分析方法,提供了对个体和抗体池的表型特征的深入了解。使用机器学习将这些测量结果与临床状态、保护/疗效结果和细胞分析数据相关联,为识别意想不到的作用机制以及深入了解可能难以解释的基本免疫学过程提供了可能性。
总结:最近的证据表明,系统的数据收集和机器学习方法的应用可以识别出在不同的 HIV-1 免疫原和疫苗方案中具有通用性的体液免疫相关性,并且可以在模型生物和临床之间进行转化。这些结果为支持这些方法的效用和进一步扩展提供了强有力的依据,这些方法不仅支持疫苗的开发,而且更广泛地定义了免疫机制。