NEW YORK – A decade after its founding, Genomics England is evolving by integrating digital pathology data with its core set of whole-genome sequencing data, particularly to improve cancer care and diagnosis of rare diseases.
The UK government organization has been talking for more than a year about its plans to work with the National Pathology Imaging Cooperative (NPIC) to build a cancer research platform that will provide investigators with a trove of genomic, phenotypic, and imaging data to inform development of new diagnostics and therapeutics.
Now, the program is broadening to include rare hereditary diseases — not just hereditary cancers — and details are starting to emerge.
Notably, NPIC is creating a pathology data repository within Genomics England's "trusted research environment," according to NPIC Operations Director Daljeet Bansal, and Genomics England is stepping up its efforts to curate and structure pathology and genomic data alike.
Prabhu Arumugam, strategic partnerships director at Genomics England and genomics director for the Data-Can national data research hub for cancer, said that it is important to make sure that the information is structured so it is machine-readable when integrating imaging and genomics. "The best bet, in our eyes, is to not [deliver] raw data" such as BAM files, he said.
This allows bioinformatics researchers to write algorithms to cross-reference knowledge about mutations and cancer spread with treatment information such as expected post-chemotherapy survival time, for example.
"If we just went from raw genome, raw image, and a raw dataset and tried to do the analysis, I think we'd get lost very easily," Arumugam said. Annotating sequences and images, standardizing terminology, and adding metatags helps avoid this conundrum.
NPIC is involved because it has become a key clinical resource for frontline physicians across England's branch of the UK National Health Service. The program, based at Leeds Teaching Hospitals NHS Trust, started as the Northern Pathology Imaging Cooperative and has since become a national effort.
Leeds Teaching Hospitals NHS trust went fully digital with pathology in 2018 in partnership with Leica Biosystems and became the de facto hub of NPIC because even though a few other trusts bought Leica Aperio GT 450 scanners to digitize pathology images, they never bothered to turn on the machines, according to Bansal.
"There was a missed opportunity," she said. "We were fortunate that we built a lab, and we've got dedicated scanners that then could do the logistical tasks of scanning all those slides." With all the scanning done at one place, Leeds could provide consistent quality control.
NPIC has become "embedded" with Genomics England as part of the Genomic Medicine Service, Bansal said.
The COVID-19 pandemic accelerated adoption and centralization of digital pathology elsewhere because the technology allowed pathologists to work from home, according to Bansal.
However, the pandemic also put the brakes on parts of the planned aggressive rollout of NHS England's Genomic Medicine Service, which was to sequence 300,000 genomes from patients with cancer or rare diseases by 2025.
"We had to back up on going live on that because of other priorities in the world," Arumugam said. "Our digitization program basically came to a halt" because clinical staff were deployed for pandemic response.
He said that COVID-19 did allow Genomics England to take the time to streamline processes such as pathology retrieval. "Whilst COVID was going, we could do some pipeline developments … so it wasn't a lost opportunity," Arumugam said. The agency was also able to improve turnaround time and results reporting.
Genomics England has not yet quantified the effect of COVID-19 on the Genomic Medicine Service in terms of how many patients were not able to get whole-genome sequencing done, however.
Arumugam said that the Genomic Medicine Service right now is "very good for rare disease" but has not been able to reach its potential in cancer care because tissue-handling processes are different for pathology and for sequencing.
The pandemic also dampened public awareness of the Genomic Medicine Service and Genomics England as a whole. "We haven't gotten to that point where [whole-genome sequencing] is routine," Arumugam said.
"But people who are [getting] a diagnosis or going through therapy or treatment know that whole-genome sequencing is an option," he added. An NHS organization called Health Education England has been tasked with educating and informing patients and clinicians alike about the availability and value of whole-genome sequencing, but the outreach is far from universal.
Arumugam said Genomics England is envisioning multimodal research into how and why tumors change over time.
"Multimodality will allow us to go to a new way of classifying a tumor," Arumugam said, making grades more specific. For example, a tumor could be called grade 2 based on where it is invading blood vessels, so the patient's medical team would be able to apply both genomic and pathology knowledge to choose therapies and more accurately predict survival.
Arumugam said that Genomics England will be "looking ultimately" at tumor clonality. But outside users such as pharma and other private-sector researchers might have their own research goals.
"They want to know how you take this to stratify patient cohorts to select specific treatments to look at who's going to relapse, and then refashion and repurpose therapeutic targets [and] find new targets," he explained.