Kumar Anurendra, Schrader Alex W, Boroojeny Ali Ebrahimpour, Asadian Marisa, Lee Juyeon, Song You Jin, Zhao Sihai Dave, Han Hee-Sun, Sinha Saurabh
College of Computing, Georgia Institute of Technology, Atlanta, GA, 30332, USA.
Department of Chemistry, University of Illinois Urbana-Champaign, Urbana, IL, 61801, USA.
Res Sq. 2023 Jan 27:rs.3.rs-2481749. doi: 10.21203/rs.3.rs-2481749/v1.
Imaging-based spatial transcriptomics technologies such as MERFISH offer snapshots of cellular processes in unprecedented detail, but new analytic tools are needed to realize their full potential. We present InSTAnT, a computational toolkit for extracting molecular relationships from spatial transcriptomics data at the intra-cellular resolution. InSTAnT detects gene pairs and modules with interesting patterns of mutual co-localization within and across cells, using specialized statistical tests and graph mining. We showcase the toolkit on datasets profiling a human cancer cell line and hypothalamic preoptic region of mouse brain. We performed rigorous statistical assessment of discovered co-localization patterns, found supporting evidence from databases and RNA interactions, and identified subcellular domains associated with RNA-colocalization. We identified several novel cell type-specific gene co-localizations in the brain. Intra-cellular spatial patterns discovered by InSTAnT mirror diverse molecular relationships, including RNA interactions and shared sub-cellular localization or function, providing a rich compendium of testable hypotheses regarding molecular functions.
基于成像的空间转录组学技术，如MERFISH，以前所未有的细节提供细胞过程的快照，但需要新的分析工具来充分发挥其潜力。我们展示了InSTAnT，这是一种用于在细胞内分辨率下从空间转录组学数据中提取分子关系的计算工具包。InSTAnT使用专门的统计测试和图挖掘，检测细胞内和细胞间具有有趣相互共定位模式的基因对和模块。我们在分析人类癌细胞系和小鼠脑下丘脑视前区的数据集上展示了该工具包。我们对发现的共定位模式进行了严格的统计评估，从数据库和RNA相互作用中找到了支持证据，并确定了与RNA共定位相关的亚细胞结构域。我们在大脑中发现了几种新的细胞类型特异性基因共定位。InSTAnT发现的细胞内空间模式反映了多种分子关系，包括RNA相互作用以及共享的亚细胞定位或功能，提供了关于分子功能的丰富可测试假设集。
