A reagent kit for spatial transcriptomic analysis

项目摘要 大规模并行单细胞基因组技术的最新进展使得 研究人员研究高分辨率的基因组和基因表达。但这些 这些技术不能保留组织内单个细胞的空间背景 由于在应用前需要细胞解离， 技术。空间基因组技术的商业可用性是稀疏的。我们有 最近与Slide-Seq技术的学术发明者一起创立了Atlas Bio， 将这项技术商业化。Slide-Seq是一种易于使用但灵敏的测量方法， 组织切片中的空间转录组，首次发表于2019年（Rodriques SG et. al，科学 2019年）。该技术利用空间条形码化的珠基质，一组酶促聚合物， 试剂和缓冲液，以及定制的生物信息学管道。它不需要任何特殊的 除了访问下一代测序器之外，还可以使用其他仪器。前两个月 公司的运作，我们已经成功地复制了生产的Slide-Seq 对底物进行空间条形码化并测试其性能。拟议第二阶段的目标 该项目旨在进一步开发Slide-Seq技术，以便广泛传播 并且可以扩展到不同的应用 和检测灵敏度。具体来说，该项目将解决可扩展性、鲁棒性和 空间条形码化基底的可制造性，其是空间条形码化基底的关键组成部分。 法我们亦会研究解决方法，方便有关技术的推广 通过开发耗材、试剂盒、生物信息学管道和基础数据 可视化工具，目标是降低进入空间转录组分析的门槛。 最后，我们将致力于提高空间转录组学技术的性能， 的空间分辨率和灵敏度，并从新鲜冷冻扩展了可用的组织类型 到FFPE。通过商业化使技术标准化，并使其可用于 更广泛的受众，我们希望加速生物学发现的新浪潮。

Project Summary Recent advances in massively parallel single cell genomic techniques have enabled researchers to study genomic and gene expression in high resolution. However, these techniques do not preserve spatial context of individual cells within the tissue and can bias representation of various cell types due to cell dissociation that is required before application of the techniques. Commercial availability of spatial genomic techniques is sparse. We have recently founded Atlas Bio with the academic inventors of the Slide-Seq technique in order to commercialize the technology. Slide-Seq is an easy-to-use yet sensitive method for measuring spatial transcriptomes in tissue slices, first published in 2019 (Rodriques SG et. al, Science 2019). The technique makes use of a spatially barcoded bead substrate, a set of enzymatic reagents and buffers, and a custom bioinformatics pipeline. It does not require any special instrumentation other than access to a next-generation sequencer. In the first two months of operation of the company, we have successfully replicated the production of the Slide-Seq spatially barcoded substrates and tested their performance. The goal of the proposed Phase II project is to further develop the Slide-Seq technology such that it can be widely disseminated and can be expanded to different applications such as those that require high spatial resolution and detection sensitivity. Specifically, the project will address the scalability, robustness, and manufacturability of the spatially barcoded substrate, which is the key component of the technique. We will also develop solutions to facilitate easy dissemination of the technology through development of consumables, reagent kits, bioinformatics pipeline, and basic data visualization tools, with the goal to lower the barrier of entry to spatial transcriptomic analyses. Lastly, we will work on improving the performance of the spatial transcriptomic technique in terms of spatial resolution and sensitivity, and expand the workable tissue type from fresh frozen to FFPE. By standardizing the technique through commercialization and making it available to a wider audience, we hope to accelerate a new wave of biological discoveries.