Tissue-wide identification of genome alterations in cancer

We aim to develop the first generation of spatially resolved DNA methodologies to uncover the underlaying molecular landscape of cancer genomes in tissues.

Our efforts will focus on a novel genome-wide technology to study genomic integrity in its spatial context, currently a major challenge in the field. The research program is based on developing new experimental protocols and new computational analysis methods.

We aim to demonstrate the utility of the method in cancer applications focusing on prostate and breast cancer that display genomic alterations with hallmarks of multiclonality, amplifications and gene fusions.We have previously demonstrated the Spatial Transcriptomics (ST) technology to successfully resolve the transcriptomic landscapes of tissue sections in situ.

This was the first demonstrated method to provide transcriptome-wide analysis in a spatial tissue context (Ståhl et al, 2016, review by Asp et al 2020).

With the establishment of the technology we have been able to develop advanced computational strategies to explore spatially barcoded transcriptomes.

We have, in a series of papers, demonstrated the value and impact to capture and link gene expression information to morphology.

For example, we have employed our know-how in (i) cell atlas projects (Asp et al, 2019; Ortiz et al, 2020) (ii) understanding temporal aspects of neurological disease (Maniatis et al, 2019, Chen et al, 2020) (iii) deconvoluting the heterogeneity in cancer (Berglund et al, 2018, Ji et al, 2020).This ambitious proposal seeks to pioneer the use of the tools to perform tissue-wide identification of genomic alterations in cancer (TWIGA) through spatial barcoding on glass slides.

This effort will enable us to, in an unsupervised manner, describe genomes in tissue sections for the first time.

We are convinced that an increased knowledge of genomic alterations in situ will improve our understanding of cancer from precancer conditions to malignancy and spread.