"The Whole Genome Story" — Visualising Structural Variation with WGS Data

 Gene expression tells you what a cell is doing right now. But cancer is, at its heart, a disease of the genome — of broken chromosomes, rearranged sequences, amplified oncogenes and deleted tumour suppressors. To understand why a gene is expressed the way it is, sometimes you need to see the structural context: the copy number landscape, the chromosomal rearrangements, the mutations that preceded everything else.

R2's WGS/NGS integration tools bring whole-genome sequencing data into the same analytical space as expression data, and the entry point is one of the most visually striking displays in the platform: the Circos plot.

A Circos plot is a circular representation of the entire genome. Each chromosome occupies an arc of the circle, and lines drawn across the interior of the circle connect genomic regions that have been rearranged relative to each other — translocations, inversions, insertions of one chromosome into another. For complex cancer genomes, these plots can look like the inside of a particularly intricate ball of string. But they carry precise biological information: which chromosomes have broken and rejoined, and where.

In R2, Circos plots for individual patient samples are pre-computed from whole-genome sequencing data and stored alongside the expression profiles of the same patients. You can navigate to a sample, open its Circos view, and immediately see its structural landscape — then jump back to the expression data to ask how that landscape connects to what the cell is transcribing.

The practical question this enables is one that molecular biologists grapple with constantly: is the unusual expression of this gene explained by a genomic event? An amplification in the region upstream of your gene of interest. A translocation that has placed an active enhancer in a new genomic neighbourhood. A deletion that has removed a key negative regulator. The WGS view makes these hypotheses testable without leaving R2.

For clinical researchers in particular, the ability to look at a patient's genome and expression profile side by side — to see the structural event and its transcriptional consequence in the same session — is a genuinely powerful diagnostic and research tool.

This is Part of an ongoing series on the R2 Genomics Analysis and Visualization Platform, developed at Amsterdam UMC. All analyses can be freely performed at r2.amc.nl. Full tutorials at r2-tutorials.readthedocs.io.