Enabling pathway analysis of RNA expression in formalin-fixed paraffin embedded tissues with the GeoMx DSP Platform

摘要

The GeoMx Digital Spatial Profiling (DSP) Platform enables robust detection of high-plex protein and RNA expression from user-defined compartments within formalin-fixed paraffin-embedded tissues. As the number of targets detected within such tissues increases, it becomes imperative to apply systems biology strategies in order to interpret the complex biology of the tumor microenvironment. In this study, we profiled expression of greater than 1600 genes by utilizing more than 10,000 DSP-specific ISH probes on FFPE samples, including colorectal cancer patient samples from which we have matching bulk RNA sequencing and nanoString analysis, as a platform for developing tools to move beyond single-gene profiling into understanding pathway-based expression profiles. The panel of genes profiled focused around capturing biological signaling along key canonical signaling pathways and cell-intrinsic signaling from immune cells and other cell types. We demonstrate the ability to leverage foundational pathway interrogation tools, including Reactome, with the data to capture spatially resolved pathway interactions and signaling within FFPE tissues. As we look towards the future of the GeoMx platform and high-plex RNA profiling of tissue samples, these experiments highlight not only the need but the capacity for this platform to derive deep understanding of the biology within and across a single slide of tissue. These experiments are being used to drive development of the software features within the GeoMx ecosystem, which will provide native support for pathway-level exploration of expression when working with highly multiplexed reagents in future platform offerings. GeoMx DSP technology is for Research Use Only and not for use in diagnostic procedures.