Integrating Multimorbidity into a Whole-Body Understanding of Disease Using Spatial Genomics.

Q4 Biochemistry, Genetics and Molecular Biology Results and Problems in Cell Differentiation Pub Date : 2022-01-01 DOI:10.1007/978-3-031-06573-6_5
Sreemol Gokuladhas, Roan E Zaied, William Schierding, Sophie Farrow, Tayaza Fadason, Justin M O'Sullivan
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Abstract

Multimorbidity is characterized by multidimensional complexity emerging from interactions between multiple diseases across levels of biological (including genetic) and environmental determinants and the complex array of interactions between and within cells, tissues and organ systems. Advances in spatial genomic research have led to an unprecedented expansion in our ability to link alterations in genome folding with changes that are associated with human disease. Studying disease-associated genetic variants in the context of the spatial genome has enabled the discovery of transcriptional regulatory programmes that potentially link dysregulated genes to disease development. However, the approaches that have been used have typically been applied to uncover pathological molecular mechanisms occurring in a specific disease-relevant tissue. These forms of reductionist, targeted investigations are not appropriate for the molecular dissection of multimorbidity that typically involves contributions from multiple tissues. In this perspective, we emphasize the importance of a whole-body understanding of multimorbidity and discuss how spatial genomics, when integrated with additional omic datasets, could provide novel insights into the molecular underpinnings of multimorbidity.

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利用空间基因组学将多发病整合到疾病的全身理解中。
多发病的特点是多种疾病在不同水平的生物(包括遗传)和环境决定因素之间的相互作用以及细胞、组织和器官系统之间和内部的一系列复杂相互作用所产生的多维复杂性。空间基因组研究的进展使我们将基因组折叠的改变与与人类疾病有关的变化联系起来的能力得到了前所未有的扩大。在空间基因组的背景下研究与疾病相关的遗传变异,能够发现转录调控程序,这些程序可能将失调基因与疾病发展联系起来。然而,已经使用的方法通常用于揭示特定疾病相关组织中发生的病理分子机制。这些形式的简化,有针对性的调查是不适合的分子解剖多病,通常涉及多个组织的贡献。从这个角度来看,我们强调了对多病的整体理解的重要性,并讨论了空间基因组学如何与其他基因组学数据集相结合,可以为多病的分子基础提供新的见解。
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来源期刊
Results and Problems in Cell Differentiation
Results and Problems in Cell Differentiation Biochemistry, Genetics and Molecular Biology-Developmental Biology
CiteScore
1.90
自引率
0.00%
发文量
21
期刊介绍: Results and Problems in Cell Differentiation is an up-to-date book series that presents and explores selected questions of cell and developmental biology. Each volume focuses on a single, well-defined topic. Reviews address basic questions and phenomena, but also provide concise information on the most recent advances. Together, the volumes provide a valuable overview of this exciting and dynamically expanding field.
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