Inside the genome revolution: five discoveries rewriting modern biology 

The £100 genome

“The Human Genome Project cost more than £2bn, but since then costs have dropped dramatically. Just ten years ago our machines could sequence a genome for around £1000. Today we can read a genome for around £200, and this might soon plumet even further – the latest machines can run for around £100 per genome.”

One of the Crick's Illumia NovaSeq X DNA sequencer is prepared for use. It can sequence a genome for £200 a fraction of the cost a decade ago. Credit: Dave Gutteridge.

Long reads, big leaps

“Genomes contain lots of repetitive sequences, which have traditionally been hard to sequence – the genomic equivalent of black holes. That all changed with the advent of techniques to read long stretches of DNA in one go – long-read sequencing. A decade ago, the technology was in its infancy and data strewn with errors. Today, advances in molecular biology and computational models have increased the accuracy to over 99.5%, enabling end-to-end sequencing of the whole human genome.”

A nanopore flow cell is loaded for long-read sequencing. This machine can produce reads over one million bases with 95.5% accuracy. Credit: Dave Gutteridge.

Cell by cell

“Until relatively recently, when we analysed DNA or RNA in a tissue sample, we had to analyse everything at once and take an average – so-called ‘bulk’ sequencing. But we can now sequence genetic material from individual cells, at scale – and it’s been revolutionary. Early single-cell techniques were cumbersome, costly, complex and limited. But a decade ago, new technology allowed us to capture and individually analyse thousands of cells at once. And even newer techniques now allow us to look simultaneously at DNA, RNA and immune activity, even from archived tissue samples, offering an unprecedented cellular portrait of life, health and disease.”

Complex single-cell techniques can look simultaneausly at multiple types of molecule – DNA, RNA and proteins thanks to sophisticated automation platforms. Credit: Dave Gutteridge.

The tissue atlas

“Traditional methods only told us what was in a sample, not where it came from. Spatial genomics changed that, combining genomics with imaging data to reveal exactly where gene activity is taking place a tissue. A decade ago, capturing this picture was labour intensive and complex, and only allowed us to look at a limited number of genes at once. But since 2019, new devices have allowed us to create spatially detailed maps of the activity of thousands of genes, with incredible detail – even to allow true single-cell resolution. It’s like going from a rough sketch to a high-res biological map.”

Machines like the NanoStrong GeoMX combine imaging and other techniques to allow researchers to quantify gene or protein expressin in specific regions of interest. Credit: Dave Gutteridge.

Beyond the code

“Our DNA contains information that goes beyond the sequence of As, Ts, Gs and Cs. The study of how cells chemically modify their DNA to regulate gene activity – epigenetics – has seen its own revolution over the last decade. A decade ago, studying these changes was slow and required large samples – early techniques to measure this, such as bisulfite sequencing and ChIP-seq were widely used but limited. Today, powerful new devices allow us to paint an incredibly detailed picture, running epigenetic studies at single-cell resolution in parallel with techniques that measure gene expression at the same time. This gives us a far more detailed picture of how genes are controlled and how that control can go wrong in disease.” 

Sophisticated equipment like this automated liquid handler simplifies manually intensive tasks, enabling the epigenome to be analysed in unprecedented detail. Credit: Dave Gutteridge.