A team of researchers developed new revolutionary software capable of transforming how we sequence DNA — hastening the pace and lowering the cost of mapping all forms of life, from yeast genomes to cancer genes, according to a recent study published in the journal Nature Biotechnology.
New gene sequencing cuts time to three, from 15 days
The new software works with portable sequencing devices to execute genetic tests and deliver diagnoses outside of labs, reports Phys.org. The new software targets, gathers, and sequences specific genes — doing away with the need to prepare samples, in addition to mapping surrounding genetic material (like conventional methods demand).
"I think this will forever change how DNA sequencing is done," said Bloomberg Distinguished Associate Professor of Computer Science and Biology Michael C. Schatz, who is also senior author of the recent study.
The new method reduces the time required for gene mutation profiling — from the conventional 15 days to a more manageable three. This means scientists can explain and diagnose conditions nearly at once, while also saving time and money via the elimination of preparation and other forms of analysis.
New software is like inventing the search bar on Netflix
"In cancer genomics there are a few dozen genes known to increase cancer risk, but with a standard sequencing run, you would have to sequence the whole genome just to read off those few genes," said Schatz, noting how adaptive sequencing enables researchers to "pick and choose which molecules we want to read and which can be skipped."
To give context to how much this invention cuts down on sequencing time, Schatz draws an analogy with Netflix: Older, conventional ways of sequencing is like making viewers watch every second of every film on Netflix to find the clip they want. Instead of this, adaptive sequencing cuts the endless irrelevant hours of content — catching unwanted films and skipping to the next entry like a search bar.
'UNCALLED' enables unprecedented flexibility
Lead author Sam Kovaka — a doctoral student at Johns Hopkins — wrote the open-source software's algorithm. Called "UNCALLED," the acronym stands for Utility for Nanopore Current Alignment to Large Expanses of DNA.
The team took two years to code, develop, and finally test the software — with a third year spent refining the algorithm enough to create results worth publishing, added Kovaka.
"UNCALLED allows for unprecedented flexibility in targeted sequencing," said Kovaka. "The fact that it's purely software-based means researchers can target any genomic region with no added cost compared to a normal sequencing run, and they can easily change targets just by running a different command."
Nanopore sequencers are like moody bouncers
The new process recognizes DNA molecules as they move through tiny electrified holes called "nanopores" — part of nanopore sequencers — which are smartphone-sized types of the bulky machines typically seen in labs. The software reads incoming data, and verifies it against a specific genome's reference sequence in no more than a fraction of a second.
The process lets specified molecules pass through the pore to undergo full mapping, but if unwanted molecules are identified, the software reverses the nanopore voltage — physically ejecting the molecule to make space for the next one.
"It's like a nightclub doorman allowing desired guests on a list to enter while rejecting the rest with a taser," said Schatz.
Future of gene sequencing in two demonstrations
Two demonstrations of UNCALLED were completed. The first one showed the enhanced sequencing of 148 genes known to exacerbate the risk of cancer via accurately and rapidly profiling all variants with only one run through a portable sequencer.
The second demonstration showed how the software can selectively sequence-specific species gathered in an environment — like microbes living on skin or in pond water. It successfully rejected molecules from verified microbes (like E. coli) to sequence those that remained — revealing a previously mysterious yeast genome.
Cutting down the time and cost needed for gene sequencing is a crucial part of an industry-wide effort to find new ways of healing damaged or dysfunctional cells on one hand, and finding new vulnerabilities in forms of life that cause illness on the other. From cancer to Parkinson's — the potential benefits of shortening DNA sequencing time and cost are as great as life itself.