GeoMx digital spatial profiler: expanding the capabilities of the CVR Virus Genomics and Bioinformatics platform
Lead Research Organisation:
University of Glasgow
Department Name: MRC Centre for Virus Research
Abstract
The CVR Viral Genomics and Bioinformatics is a team of scientists which use sequencing techniques and computational methods to understand viral infections.
Scientists working on genomics and bioinformatics use DNA sequencing to determine the sequence of nucleotides within a DNA molecule. Every organism has a unique sequence of nucleotides, including viruses, and we can use that sequence to understand many aspects of their biology. At the CVR, the Viral Genomics and Bioinformatics team also does RNA sequencing (RNA-seq). This is a type of experiment that measures the expression of genes. In other words, we determine which of the genes encoded by our DNA are turned on or off and at what extent. This is particularly useful to understand how our cells respond when they become infected by viruses, ultimately leading to clues on the mechanisms by which viruses cause disease.
We know that tissues are a complex grouping of different cell types, and that each cell type may respond differently to a viral infection. We also know that tissues can have compartments and that spatial information is important during infection. However, the protocols most frequently used by the research community require homogenisation of tissues in a single mixture, containing all the RNA molecules. This means that all the information provided by each individual cell, as well as the spatial context is lost.
In this application, we are applying for funds to invest in a new technology that retains the spatial information. With the GeoMx from NanoString, we retrieve RNA-seq information from the tissues while maintaining the spatial context. This is important because it enables us to visualise how different cells or areas of a tissue are turning their genes on and off and overlap that information with images which indicate where in the tissue is the infection taking place or if are there any lesions, amongst other features.
Overall, this new instrument will enable us to understand how viruses infect us based on RNA-seq data from different cell types, spatial data and other characteristics of the tissues, enabling a more complete view of infections and how we respond to them.
Scientists working on genomics and bioinformatics use DNA sequencing to determine the sequence of nucleotides within a DNA molecule. Every organism has a unique sequence of nucleotides, including viruses, and we can use that sequence to understand many aspects of their biology. At the CVR, the Viral Genomics and Bioinformatics team also does RNA sequencing (RNA-seq). This is a type of experiment that measures the expression of genes. In other words, we determine which of the genes encoded by our DNA are turned on or off and at what extent. This is particularly useful to understand how our cells respond when they become infected by viruses, ultimately leading to clues on the mechanisms by which viruses cause disease.
We know that tissues are a complex grouping of different cell types, and that each cell type may respond differently to a viral infection. We also know that tissues can have compartments and that spatial information is important during infection. However, the protocols most frequently used by the research community require homogenisation of tissues in a single mixture, containing all the RNA molecules. This means that all the information provided by each individual cell, as well as the spatial context is lost.
In this application, we are applying for funds to invest in a new technology that retains the spatial information. With the GeoMx from NanoString, we retrieve RNA-seq information from the tissues while maintaining the spatial context. This is important because it enables us to visualise how different cells or areas of a tissue are turning their genes on and off and overlap that information with images which indicate where in the tissue is the infection taking place or if are there any lesions, amongst other features.
Overall, this new instrument will enable us to understand how viruses infect us based on RNA-seq data from different cell types, spatial data and other characteristics of the tissues, enabling a more complete view of infections and how we respond to them.
Technical Summary
We support CVR researchers and external collaborators across a range of virus-focused research projects, providing specialist expertise, resources and training to the wider UK and international virology community. Specifically, we generate and analyse viral genome sequences, metagenomic and transcriptomics data, and support specific projects on virus detection and drug resistance monitoring, infection studies, virus epidemiology studies, cross-species transmission, and the evolutionary origins of viruses. In addition, we develop bespoke software and online tools to analyse and make accessible data on virus sequences.
We aim to build on the Viral Genomics and Bioinformatics (VGB) expertise and align it with the recent expansion at the CVR on the use of in vivo experimental systems, and analyses of clinical material. With this proposal, we aim to understand the evolutionary, spatial, temporal, and phenotypic dimensions of infection by sequencing-based methodologies. These methodologies include newly adopted single-cell and spatial omics, in addition to the established bulk transcriptomics. The strength of VGB is that we have the expertise to integrate several layers of data generated locally (and available in public databases) to further extend our understanding of virus infections.
The goal of this proposal is to invest in a "GeoMx spatial digital profiler" to expand our capabilities with digital pathology applications. This instrument, uniquely integrates the power of microscopy, enabling detection of up to four fluorescent markers, with the power of transcriptomics and multiplexed protein detection, while maintaining information on the spatial context. The addition of this instrument to our repertoire will provide unique capabilities to the CVR.
We aim to build on the Viral Genomics and Bioinformatics (VGB) expertise and align it with the recent expansion at the CVR on the use of in vivo experimental systems, and analyses of clinical material. With this proposal, we aim to understand the evolutionary, spatial, temporal, and phenotypic dimensions of infection by sequencing-based methodologies. These methodologies include newly adopted single-cell and spatial omics, in addition to the established bulk transcriptomics. The strength of VGB is that we have the expertise to integrate several layers of data generated locally (and available in public databases) to further extend our understanding of virus infections.
The goal of this proposal is to invest in a "GeoMx spatial digital profiler" to expand our capabilities with digital pathology applications. This instrument, uniquely integrates the power of microscopy, enabling detection of up to four fluorescent markers, with the power of transcriptomics and multiplexed protein detection, while maintaining information on the spatial context. The addition of this instrument to our repertoire will provide unique capabilities to the CVR.
