The dawn of spatial omics

• 成果类型: Review
• 署名作者: Bressan, Dario; Battistoni, Giorgia; Hannon, Gregory J.
• 署名单位: Cancer Research UK; CRUK Cambridge Institute; University of Cambridge
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-12094
• DOI: 10.1126/science.abq4964
• 发表日期: 2023-08-04
• 页码: 499-+
• 关键词: genome-wide expression; single-cell; breast-cancer; gene-expression; messenger-rna; subcellular resolution; mass cytometry; Visualization; tissue; seq

摘要

BACKGROUNDJust as single-cell sequencing has revolutionized many fields of biology, spatial omics, in which molecular parameters are measured in situ on intact tissue samples, is set to empower a new generation of scientific discoveries. A plethora of new technologies now enable spatial profiling of gene and protein expression, genetic mutations, epigenetic marks, chromatin structure, and genome organization. Most of these methods trace back to traditional techniques such as immunohistochemistry and in situ hybridization, or leverage the throughput of next-generation sequencing by converting spatial coordinates to sequence barcodes. Spatial omics technologies operate at vastly different levels of resolution, sensitivity, and throughput. There are also considerable differences in ease of adoption, compatibility with different sample types, commercial availability, upfront investment, and cost per sample. In such a rich and constantly evolving field, choosing the best technology to address a specific biological challenge-carefully weighting the strengths and weaknesses of each-is critical.ADVANCESThe field of spatial molecular profiling has come of age over the past few years. Current RNA profiling technologies allow the spatial measurement of gene expression for centimeter-scale samples-in many cases, at single-cell resolution. Targeted methods can quantify thousands of transcripts, including those of very low abundance, whereas untargeted protocols offer transcriptome-wide profiling and can even detect gene isoforms and mutations, with coverage approaching that of disaggregated single-cell methods. Multiplexed immunohistochemistry protocols, either based on mass spectrometry or fluorescence imaging, can similarly be used to profile tens to hundreds of protein markers on a wide range of samples. Recent studies have reported additional approaches that recover other types of molecular information, including the spatial profiling of genomic organization for thousands of loci, open chromatin and epigenetic marks, and untargeted in situ DNA sequencing. Multi-omic technologies capturing multiple sources of information at once are also becoming available. As these methods become more reliable and widely adopted, it is becoming increasingly clear that spatial omics will contribute substantially to the elucidation of many biological questions, with prominent examples in fields ranging from oncology (such as the study of tumor heterogeneity and microenvironment) to neuroscience and organismal development.OUTLOOKFuture development trends in the spatial omic area are needed in three main areas: (i) multi-omics, which is defined as the simultaneous measurement of different parameters (for example, DNA, RNA, and protein); (ii) increased access and democratization, with technologies becoming more readily available, more reliable, and more robust; and (iii) improved analysis frameworks. As technologies continue to evolve, it will become necessary to dedicate more attention to data analysis and experimental design. Spatial omics technologies can already generate many terabytes of data in a single experiment, creating substantial challenges in data processing, analysis, and visualization. Statistical methods and guidelines for sample replication, study design, and batch correction are also lagging behind, although they're evolving rapidly.