Challenges and Opportunities in the Clinical Translation of High-Resolution Spatial Transcriptomics.

Tancredi Massimo Pentimalli, Nikos Karaiskos, Nikolaus Rajewsky
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Abstract

Pathology has always been fueled by technological advances. Histology powered the study of tissue architecture at single-cell resolution and remains a cornerstone of clinical pathology today. In the last decade, next-generation sequencing has become informative for the targeted treatment of many diseases, demonstrating the importance of genome-scale molecular information for personalized medicine. Today, revolutionary developments in spatial transcriptomics technologies digitalize gene expression at subcellular resolution in intact tissue sections, enabling the computational analysis of cell types, cellular phenotypes, and cell-cell communication in routinely collected and archival clinical samples. Here we review how such molecular microscopes work, highlight their potential to identify disease mechanisms and guide personalized therapies, and provide guidance for clinical study design. Finally, we discuss remaining challenges to the swift translation of high-resolution spatial transcriptomics technologies and how integration of multimodal readouts and deep learning approaches is bringing us closer to a holistic understanding of tissue biology and pathology.

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高分辨率空间转录组学临床转化的挑战与机遇。
病理学的发展始终离不开技术的进步。组织学推动了单细胞分辨率的组织结构研究,至今仍是临床病理学的基石。在过去十年中,新一代测序技术为许多疾病的靶向治疗提供了信息,证明了基因组规模的分子信息对个性化医疗的重要性。如今,空间转录组学技术的革命性发展将完整组织切片中亚细胞分辨率的基因表达数字化,从而能够对常规收集和存档临床样本中的细胞类型、细胞表型和细胞间通讯进行计算分析。在此,我们回顾了此类分子显微镜的工作原理,强调了它们在确定疾病机制和指导个性化疗法方面的潜力,并为临床研究设计提供了指导。最后,我们将讨论在快速转化高分辨率空间转录组学技术方面仍然存在的挑战,以及多模态读数和深度学习方法的整合如何使我们更接近于全面了解组织生物学和病理学。
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来源期刊
CiteScore
62.60
自引率
0.00%
发文量
40
期刊介绍: The Annual Review of Pathology: Mechanisms of Disease is a scholarly journal that has been published since 2006. Its primary focus is to provide a comprehensive overview of recent advancements in our knowledge of the causes and development of significant human diseases. The journal places particular emphasis on exploring the current and evolving concepts of disease pathogenesis, as well as the molecular genetic and morphological changes associated with various diseases. Additionally, the journal addresses the clinical significance of these findings. In order to increase accessibility and promote the broad dissemination of research, the current volume of the journal has transitioned from a gated subscription model to an open access format. This change has been made possible through the Annual Reviews' Subscribe to Open program, which allows all articles published in this volume to be freely accessible to readers. As part of this transition, all articles in the journal are published under a Creative Commons Attribution (CC BY) license, which encourages open sharing and use of the research.
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