DISCOVERY OF THE MONTH: Same Day Genome Sequencing
- malihaybhat
- Oct 26
- 5 min read
Updated: Oct 26
Subject Articles:
Backstory
June 26, 2000. That was the day that revolutionist Craig Venter alongside Francis Collins of the publicly funded Human Genome Project (HGP) co-announced the first fully decoded working draft of the human genome; this groundbreaking news was announced at a White House ceremony, presided by President Bill Clinton. Ventor's company, Celera Geomics, started their project in September of 1999 and took 9 months to complete the initial draft. By contrast, the HGP had started their project in 1990 and took around 10 years to complete the same draft. Celera published its draft of the human genome in the journal Science, just a day after the HGP published theirs in Nature in 2001. At the time, their work was nothing short of miraculous, as they were able to do something that was unimaginable to most.
Fast forward to today, Wojcik et al published a paper in The New England Journal of Medicine illustrating the utility of same-day genomic sequencing in a critical care setting. The notion that something that took hundreds of people years to figure out can now be done in less than a day fascinated me, but also was confusing, so I chose to write this post to simplify their process and maybe help translate that same fascination to you! In this blog post, I'm going to first explain a little bit about the process of mapping a human's genome, and after I'm going to review the article explaining the new method being tested - I hope you enjoy!
How the Human Genome is Mapped
Image pulled from article describes/simplifies process of sequencing DNA
Whole Genome Sequencing (WGS) is a process scientists use to read the complete DNA code of an organism, which is made up of four letters (A, T, C, and G). It starts when scientists take cells from an organism and break them open to release the DNA, which is then purified. Because the DNA strand is too long to analyze all at once, it’s cut into smaller pieces using special enzymes. These pieces are then copied many times using a method called PCR (Polymerase Chain Reaction) to create what’s known as a DNA library. Next, the DNA library is placed into a sequencing machine, which reads the order of the DNA letters in each fragment. Finally, powerful computer programs take all those short reads and piece them together like a jigsaw puzzle, creating a complete map of the genome. This map helps scientists understand how genes work, identify mutations, and even track how diseases spread. While the process has improved drastically from the years it took to first map the human genome, it still takes around two to five days (realistically in real life setting a week or so), meaning it can’t yet be used in time-sensitive or critical care situations.
Same-Day Sequencing
Normally, genome sequencing works by splitting the DNA in half and using one of the real base pairs from the DNA (the A, T, C, and G found naturally in our cells). Scientists then fill in the matching base from another substance to form a complete double strand, which can be read by sequencing machines. While this process is accurate, it’s time-consuming and requires a lot of specialized equipment.
The new method, called sequencing by expansion, changes that completely. Instead of using natural DNA bases, it uses mechanically engineered base pairs that are enlarged. Because this replicated DNA is made from larger, easier-to-detect bases, scientists don’t need all the complex machinery or long wait times. This allows for key steps like “integrated base calling, formation of a consensus read, and genome alignment” to happen much faster, and almost at the same time as sequencing itself.
Even more impressive, since the sequencing data is so straightforward to read, computers can process it in real time. They can map the entire genome using binary numbers (a digital code of 0s and 1s) in about 30 minutes. That means scientists can get a fully sequenced and analyzed genome nearly simultaneously with the end of the sequencing run.
While rapid sequencing like this isn’t yet used in every hospital, its potential is huge. As the article notes, “rapid genetic diagnosis is increasingly used in critical care management, particularly in neonatal intensive care units (NICUs).” But since most critical care decisions need to happen within hours, same-day sequencing could soon make life-saving genetic information available when it’s needed most.
Their Clinical Trial
Image pulled from article shows process & time stamps from blood sample to full report
This article was specific to NICUs (intensive care unit for newborns), and these scientists "sequenced and analyzed 15 human genomes on the prototype of sequencing by expansion." Here are the lab statistics and their findings:
Out of 15: 3 human samples came from National Institute of Standards and Technology (control)
Out of 15: 5 patients whose genomes were previously sequenced and known (retrospective)
Out of 15: 7 patients in the NICU from a prospective set (with parent consent)
Mean time to generate variants from genomic DNA: 4 hours 4 minutes
Blood samples arrived at 7 a.m., reports fully interpreted from 2 p.m. to 4:30 p.m.
Quickest time from sample receipt to report: 6 hours 47 minutes.
Out of 7 NICU patients, there were two positive findings and 5 negative findings - all 7 produced actionable results if this clinical trial was first-line.
To expand, infant 3, who had several physical abnormalities, was found to have an unbalanced translocation between chromosomes 10 and 14, which explained the developmental issues doctors had observed. Infant 7, who was experiencing tonic seizures, had a mutation in the KCNQ2 gene, a known cause of genetic epilepsy that responds well to sodium-channel blocker medications. By identifying this mutation so quickly, doctors were able to link the seizures to a treatable condition and theoretically would be able to start treatment immediately.
My Closing Thoughts
To give context, same-day genomic sequencing has been achieved prior to this, but these findings are significant because they bridge the technology to real world use. That is why this advancement is meaningful, especially in neonatal intensive care units. Because DNA is permanent and unchanging, being able to identify a genetic anomaly within hours gives doctors information they can trust for a patient’s entire life. Same-day sequencing means that instead of waiting days for results, medical teams can make immediate, informed decisions that prevent harm and guide treatment based on the baby’s exact genetic makeup. To go from taking years to now, taking one day to extract life-changing findings represents a major step toward a future where precision medicine isn’t just fast - it’s fast enough to save lives when every minute matters.
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