News, Analysis, Trends, Management Innovations for
Clinical Laboratories and Pathology Groups

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Clinical Laboratories and Pathology Groups

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Artificial Intelligence in the Operating Room: Dutch Scientists Develop AI Application That Informs Surgical Decision Making during Cancer Surgery

Speedy DNA sequencing and on-the-spot digital imaging may change the future of anatomic pathology procedures during surgery

Researchers at the Center for Molecular Medicine (CMM) at UMC Utrecht, a leading international university medical center in the Netherlands, have paired artificial intelligence (AI) and machine learning with DNA sequencing to develop a diagnostic tool cancer surgeons can use during surgeries to determine in minutes—while the patient is still on the operating table—whether they have fully removed all the cancerous tissue.

The method, “involves a computer scanning segments of a tumor’s DNA and alighting on certain chemical modifications that can yield a detailed diagnosis of the type and even subtype of the brain tumor,” according to The New York Times, which added, “That diagnosis, generated during the early stages of an hours-long surgery, can help surgeons decide how aggressively to operate, … In the future, the method may also help steer doctors toward treatments tailored for a specific subtype of tumor.”

This technology has the potential to reduce the need for frozen sections, should additional development and studies confirm that it accurately and reliably shows surgeons that all cancerous cells were fully removed. Many anatomic pathologists would welcome such a development because of the time pressure and stress associated with this procedure. Pathologists know that the patient is still in surgery and the surgeons are waiting for the results of the frozen section. Most pathologists would consider fewer frozen sections—with better patient outcomes—to be an improvement in patient care.

The UMC Utrecht scientist published their findings in the journal Nature titled, “Ultra-Fast Deep-Learned CNS Tumor Classification during Surgery.”

 “It’s imperative that the tumor subtype is known at the time of surgery,” Jeroen de Ridder, PhD (above), associate professor in the Center for Molecular Medicine at UMC Utrecht and one of the study leaders, told The New York Times. “What we have now uniquely enabled is to allow this very fine-grained, robust, detailed diagnosis to be performed already during the surgery. It can figure out itself what it’s looking at and make a robust classification,” he added. How this discovery affects the role of anatomic pathologists and pathology laboratories during cancer surgeries remains to be seen. (Photo copyright: UMC Utrecht.)

Rapid DNA Sequencing Impacts Brain Tumor Surgeries

The UMC Utrecht scientists employed Oxford Nanopore’s “real-time DNA sequencing technology to address the challenges posed by central nervous system (CNS) tumors, one of the most lethal type of tumor, especially among children,” according to an Oxford Nanopore news release.

The researchers called their new machine learning AI application the “Sturgeon.”

According to The New York Times, “The new method uses a faster genetic sequencing technique and applies it only to a small slice of the cellular genome, allowing it to return results before a surgeon has started operating on the edges of a tumor.”

Jeroen de Ridder, PhD, an associate professor in the Center for Molecular Medicine at UMC Utrecht, told The New York Times that Sturgeon is “powerful enough to deliver a diagnosis with sparse genetic data, akin to someone recognizing an image based on only 1% of its pixels, and from an unknown portion of the image.” Ridder is also a principal investigator at the Oncode Institute, an independent research center in the Netherlands.

The researchers tested Sturgeon during 25 live brain surgeries and compared the results to an anatomic pathologist’s standard method of microscope tissue examination. “The new approach delivered 18 correct diagnoses and failed to reach the needed confidence threshold in the other seven cases. It turned around its diagnoses in less than 90 minutes, the study reported—short enough for it to inform decisions during an operation,” The New York Times reported.

But there were issues. Where the minute samples contain healthy brain tissue, identifying an adequate number of tumor markers could become problematic. Under those conditions, surgeons can ask an anatomic pathologist to “flag the [tissue samples] with the most tumor for sequencing, said PhD candidate Marc Pagès-Gallego, a bioinformatician at UMC Utrecht and a co-author of the study,” The New York Times noted. 

“Implementation itself is less straightforward than often suggested,” Sebastian Brandner, MD, a professor of neuropathology at University College London, told The Times. “Sequencing and classifying tumor cells often still required significant expertise in bioinformatics as well as workers who are able to run, troubleshoot, and repair the technology,” he added. 

“Brain tumors are also the most well-suited to being classified by the chemical modifications that the new method analyzes; not all cancers can be diagnosed that way,” The Times pointed out.

Thus, the research continues. The new method is being applied to other surgical samples as well. The study authors said other facilities are utilizing the method on their own surgical tissue samples, “suggesting that it can work in other people’s hands.” But more work is needed, The Times reported.

UMC Utrecht Researchers Receive Hanarth Grant

To expand their research into the Sturgeon’s capabilities, the UMC Utrecht research team recently received funds from the Hanarth Fonds, which was founded in 2018 to “promote and enhance the use of artificial intelligence and machine learning to improve the diagnosis, treatment, and outcome of patients with cancer,” according to the organization’s website.

The researchers will investigate ways the Sturgeon AI algorithm can be used to identify tumors of the central nervous system during surgery, a UMC Utrecht news release states. These type of tumors, according to the researchers, are difficult to examine without surgery.

“This poses a challenge for neurosurgeons. They have to operate on a tumor without knowing what type of tumor it is. As a result, there is a chance that the patient will need another operation,” said de Ridder in the news release.

The Sturgeon application solves this problem. It identifies the “exact type of tumor during surgery. This allows the appropriate surgical strategy to be applied immediately,” the news release notes.

The Hanarth funds will enable Jeroen and his team to develop a variant of the Sturgeon that uses “cerebrospinal fluid instead of (part of) the tumor. This will allow the type of tumor to be determined already before surgery. The main challenge is that cerebrospinal fluid contains a mixture of tumor and normal DNA. AI models will be trained to take this into account.”

The UMC Utrecht scientists’ breakthrough is another example of how organizations and research groups are working to shorten time to answer, compared to standard anatomic pathology methods. They are combining developing technologies in ways that achieve these goals.

—Kristin Althea O’Connor

Related Information:

Ultra-fast Deep-Learned CNS Tumor Classification during Surgery

New AI Tool Diagnoses Brain Tumors on the Operating Table

Pediatric Brain Tumor Types Revealed Mid-Surgery with Nanopore Sequencing and AI

AI Speeds Up Identification Brain Tumor Type

Four New Cancer Research Projects at UMC Utrecht Receive Hanarth Grants

Rapid Nanopore Sequencing, Machine Learning Enable Tumor Classification during Surgery

Major Breakthrough in Human Genome Sequencing, as Full Y Chromosome Sequencing Completed after a More than 20 Year Journey

Clinical laboratories and pathology groups may soon have new assays for diagnosis, treatment identification, patient monitoring

It’s here at last! The human Y chromosome now has a full and complete sequence. This achievement by an international team of genetic researchers is expected to open the door to significant insights in how variants and mutations in the Y chromosome are involved in various diseases and health conditions. In turn, these insights could lead to new diagnostic assays for use by clinical laboratories and pathology groups.

After decades of attempts, genetic scientists led by the Telomere-to-Telomere Consortium—a team of researchers funded by the National Human Genome Research Institute (NHGRI), part of the National Institutes of Health (NIH)—have finally “generated the first truly complete sequence of a human Y chromosome,” which is “the final human chromosome to be fully sequenced,” of the 24 human chromosomes, SciTechDaily reported.

Pathologists and clinical laboratories involved in genetic research will understand the significance of this accomplishment. The full Y chromosome sequence “fills in gaps across more than 50% of the Y chromosome’s length, [and] uncovers important genomic features with implications for fertility, such as factors in sperm production,” SciTechDaily noted.

This breakthrough will make it possible for other research teams to gain further understanding of the functions of the Y chromosome and how specific gene variants and mutations contribute to specific health conditions and diseases. In turn, knowledge of those genetic sequences and mutations would give clinical laboratories the assays that help diagnosis, identify relevant therapies, and monitor a patient’s progress.

The researchers published their findings in the journal Nature titled, “The Complete Sequence of a Human Y Chromosome.”

“When you find variation that you haven’t seen before, the hope is always that those genomic variants will be important for understanding human health,” said Adam Phillippy, PhD, a senior investigator and head of the Genome Informatics Section at the National Human Genome Research Institute, in a press release. Clinical laboratories and anatomic pathology groups may soon have new assays based on the T2T study findings. (Photo copyright: National Human Genome Research Institute.)

Study Background and Recognition

Revolutionary thinking by the Telomere-to-Telomere (T2T) scientists led to the team’s breakthrough. The researchers “applied new DNA sequencing technologies and sequence assembly methods, as well as knowledge gained from generating the first gapless sequences for the other 23 human chromosomes,” SciTechDaily reported.

In 1977, the first complete genome of an organism was sequenced. Thus began the commencement of sequencing technology research. Twenty years ago the first human genome sequence was completed. The result was thanks to years of work through the preferred “chain termination” (aka, Sanger Sequencing) method developed by Fred Sanger and a $2.7 billion contribution from the Human Genome Project, according to a study published in the African Journal of Laboratory Medicine (AJLM).

By 2005, a new era in genomic sequencing emerged. Scientists now employed a technique called pyrosequencing and the change had great benefits. “Massively parallel or next-generation sequencing (NGS) technologies eliminated the need for multiple personnel working on a genome by automating DNA cleavage, amplification, and parallel short-read sequencing on a single instrument, thereby lowering costs and increasing throughput,” the AJLM paper noted.

The new technique brought great results. “Next-generation sequencing technologies have made sequencing much easier, faster and cheaper than Sanger sequencing,” the AJLM study authors noted.

The changes allowed more sequencing to be completed. Nevertheless, more than half of the Y chromosome sequence was still unknown until the new findings from the T2T study, SciTechDaily reported.

Why the TDT Breakthrough Is So Important

“The biggest surprise was how organized the repeats are,” said Adam Phillippy, PhD, a senior investigator and head of the NHGRI. “We didn’t know what exactly made up the missing sequence. It could have been very chaotic, but instead, nearly half of the chromosome is made of alternating blocks of two specific repeating sequences known as satellite DNA. It makes a beautiful, quilt-like pattern.”

Phillippy’s research was groundbreaking enough to earn him and his team finalist positions in the 2023 Science, Technology, and Environment segment of the Samuel J. Heyman Service to America Medals.

Much can be gained in knowing more about the Y chromosome. Along with the X chromosome, it is significant in sexual development. Additionally, current research is showing that genes on the Y chromosome are linked to the risk and severity of cancer.

Might What Comes Next Give Clinical Labs New Diagnostic Tools?

The variety of new regions of the Y chromosome that the T2T team discovered bring into focus several areas of new genetic research. For instance, the “azoospermia factor region, a stretch of DNA containing several genes known to be involved in sperm production” was uncovered, and “with the newly completed sequence, the researchers studied the structure of a set of inverted repeats or palindromes in the azoospermia factor region,” SciTechDaily reported.

“This structure is very important because occasionally these palindromes can create loops of DNA. Sometimes, these loops accidentally get cut off and create deletions in the genome,” said Arang Rhie, PhD, a staff scientist at NHGRI and first author of the Nature study.

Missing regions would challenge the production of sperm, impacting fertility, so being able to finally see a complete sequence will help research in this area.

Scientists are only just beginning to recognize the value of this breakthrough to future genetic research and development. As genetic sequencing costs continue to drop, the T2T research findings could mean new treatment options for pathologists and diagnostic assays for clinical laboratories are just around the corner.

—Kristin Althea O’Connor

Related Information:

Complete Human Y Chromosome Sequence Assembled for the First Time

The Complete Sequence of a Human Y Chromosome

Scientists Release the First Complete Sequence of a Human Y Chromosome

Will Long-Read Sequencing Technologies Replace Short-Read Sequencing Technologies in the Next 10 Years?

Researchers Assemble the First Complete Sequence of a Human Y Chromosome

Adam Phillippy Finalist in Samuel J. Heyman Service to America Medals for Science, Technology, and Environment

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