The era of fast and cheap genome sequencing has arrived

Comparing these genomes to those of people without schizophrenia has allowed researchers to discover several genes that have a profound impact on a person’s risk of developing it. By being able to sequence more genomes faster and more cheaply, Gabriel says they will be able to find additional genes that have a more subtle effect on disease. “Once you have larger data, the signal becomes clearer,” she says.

“It’s the kind of thing that shakes up everything you’re working on,” agrees Jeremy Schmutz, a researcher at the HudsonAlpha Institute of Biotechnology, of the new sequencing technology. “This reduction in sequencing costs allows you to scale up and do more of these large research studies.” For Schmutz, who studies plants, cheaper sequencing will allow him to generate more reference genomes to better study how genetics influence a plant’s physical characteristics or phenotype. Large genomic studies can help improve agriculture by accelerating the selection of certain desirable crops, he says.

Illumina sequencers use a method called “sequencing by synthesis” to decipher DNA. This process first requires the DNA strands, which are usually in the form of a double helix, to be split into single strands. The DNA is then split into short fragments which are spread out on a flow cell, a glass surface the size of a smartphone. When a flow cell is loaded into the sequencer, the machine attaches color-coded fluorescent labels to each base: A, C, G, and T. For example, blue might correspond to the letter A. Each of the DNA fragments is copied one base at a time, and a corresponding DNA strand is gradually made or synthesized. A laser scans the bases one by one while a camera records the color code of each letter. The process is repeated until each fragment is sequenced.

For its latest machines, Illumina has invented denser flow cells to increase data throughput and new chemical reagents, which allow for faster base reads. “The molecules of this sequencing chemistry are much stronger. They can withstand heat, they can withstand water, and because they’re so much tougher, we can subject them to more laser power and scan them faster. It’s the heart of the engine that allows us to get a lot more data faster and at a lower cost,” said Alex Aravanis, Illumina’s chief technology officer.

That said, while the cost per genome is down, for now the cost of starting a machine itself is high. Illumina’s new system will cost around $1 million, about the same price as its existing machines. The high price is one of the main reasons why they are not yet common in small laboratories and hospitals, or in rural areas.

Another is that they also need experts to operate the machines and process the data. But Illumina’s sequencers are fully automated and produce a report comparing each sample to a reference genome. Aravanis says this automation could democratize sequencing, so that facilities without large teams of scientists and engineers can run the machines with few resources. The system also stores data on an internal computer, whereas with previous models this data had to be stored elsewhere.