Scalable spatial DNA sequencing from archival tissue maps copy number subclones
Spatially resolved DNA sequencing holds promise due to its potential utility in understanding cancer intra-tumour heterogeneity and tumour evolution in relation to tissue architecture. However, it has so far been used to a limited extent due to technical challenges and high cost of existing methods. Hence we aimed to develop a high throughput spatial genomic assay to obtain copy number alteration…
Scalable spatial DNA sequencing from archival tissue can help reveal copy number subclones, according to a new study. This method, called Adaptive Resolution Multiscale Spatial DNA sequencing (ARMS DNAseq), overcomes technical challenges and high costs of existing spatial genomic assays. By using ultra-low coverage whole genome sequencing at sub-millimeter resolution, ARMS DNAseq can profile copy number alterations (CNAs) at user-defined spatial resolution.
The researchers applied the technique to profile CNAs from over 766 regions (tiles) from 3 patients, covering an area of more than 300 mm2. With ARMS DNAseq, the team was able to better understand tumour evolution in a spatial context and identify tumour subclones that were previously obscured or incompletely represented in bulk multi-region whole genome sequencing.
Furthermore, the study revealed associations between tumour subclones and morphology, as well as predictions of subclone identity from deep learning-derived image representations. Finally, the researchers demonstrated how ARMS DNAseq integrates with spatial transcriptomic data, showing subclone-specific immune cell co-occurrence and transcriptional programmes cutting across subclone boundaries.
This scalable and adaptable workflow for direct spatial copy number profiling from archival tissue sections represents a significant advancement in the field of spatial genomic analysis.
Written by urgent.news from bioRxiv's reporting — not their text. Machine-written — may contain errors; check the original before relying on it.
