Genomic sequencing is taking on a growing role in how public health (PH) labs detect, monitor, and respond to infectious threats. Despite the advancements in next-generation sequencing (NGS) and metagenomics, there are still important challenges and opportunities for regional PH labs around sequencing. To learn more about how lab managers can make good decisions about introducing genomics technology into their labs, we talked with three experts in this technology: Genay Pilarowski, PhD, (GP) senior scientist on the rapid response team at the Chan Zuckerberg Biohub–San Francisco; Mark Pandori, PhD, (MP) chief of laboratory services for the Sacramento County Public Health Laboratory; and Jason Smith, (JS) business lead, strategic, infectious disease and microbiology at Illumina.
Q: What are the biggest challenges facing public health laboratory surveillance programs today, and how can advances in sequencing technology help address them?
MP: “PH laboratories have become adept at generating raw sequencing data in the “wet lab” capacity. What they lack are the tools and expertise to operationalize it for PH departments and infection control departments at customer hospitals. What often happens is that a third party has to be brought in to help the non-laboratory customers use the data to execute their work more effectively. When they did that, it was remarkable. We reduced the number and time of unnecessary investigations and found outbreaks faster than without sequencing.”
Q: How has genomics changed pathogen surveillance in the last five years and how can public health labs evolve to keep up?
MP: “PH laboratories have been relegated in recent decades to running “Boolean” lab tests, like PCR or TMA, to detect PH–relevant pathogens. But in doing so, they aren’t even major players in generating the amount of data needed to support surveillance programs. Moreover, what little data they contribute is non-descriptive; it says nothing about virulence or drug susceptibility. In this way, PH labs have lost their relevance and their claim to being “reference labs”.
PH labs need to recapture their role. That means embracing that they are, in fact, an intelligence agency. They need to be the labs that describe the threats and not merely detect them. The only technology that can singularly bring this reference lab status to PH labs is NGS. PH labs can and should evolve to make NGS the centerpiece of their platforms. California has excellent regulations that require isolates of PH relevance to go to PH labs. PH labs should take full advantage and sequence all of them, generate intelligence, and then use that capability to rebuild their reference lab status.”
GP: “We primarily use non-targeted metagenomic sequencing to kick off surveillance studies, and this first step allows programs to see the pathogen landscape in their communities and study areas, rather than guessing what pathogens should be prioritized. From there, data-driven community-targeted pathogen surveillance programs can be developed with the appropriate tools selected. It can enable something like “precision surveillance”. On the other hand, non-targeted metagenomic sequencing can be used to catch anything that might be there, which, when implemented strategically, can detect patterns before we know to look for them. I don’t think PH labs that onboard sequencing will have a hard time keeping up, as they will quickly see the doors that sequencing opens for questions they want and need to answer.”
Q: What operational challenges should public health laboratories anticipate when implementing sequencing-based surveillance programs?
CREDIT: Illumina
GP: “Implementing sequencing can be intimidating at first because it’s new, but once a lab gets started, I think they’ll see that it is very possible. Having a point person who will champion the onboarding and carry the technology in the lab will be critical, and finding resources in others who have experience doing what you are trying to build will also ease onboarding. For the analysis, there are lots of resources online, communities that support each other, and new AI tools that have lowered the barrier for laboratory scientists who want and need to analyze their own genomic data.”
MP: “Bioinformatics software does not equal automatic translation of the data to infection control and to PH disease controllers. There needs to be “buy-in” and training for non-laboratorians to learn how to use this kind of data. Labs are not good teachers of this.”
Q: How has genomic surveillance changed the way public health laboratories respond to outbreaks compared with traditional approaches?
GP: “Genomic surveillance can not only provide a positive/negative answer about the presence of a pathogen, but also detailed genetic information, which can provide insights into transmission patterns and help inform epidemiological investigations. This additional tool improves the speed, quality, and economics of investigations.”
MP: “In Alameda County, where we replaced all bacteriology with NGS-based identification, we found that NGS changed the process. Previously, the epidemiologists and disease control people at PH departments would make or be informed of an observation, like an outbreak. They would investigate. At some point, the lab would get isolates and send them to the CDC or a state lab. A few months later, the outbreak would have resolved and would have been defined by expert investigators. Then the lab gets the sequencing data and the analysis and says, “Hey, you guys were right!” Now, if the lab sequences routinely and quickly, it can generate data, see connections in cases, and identify problems.”
JS: “With the adoption of streamlined workflows of NGS toward genomic pathogen surveillance, more comprehensive and scalable approaches to PH action have been enabled.”
Q: What have you learned from deploying sequencing technologies in real-world public health settings that might surprise laboratory leaders?
MP: “That you will make discoveries in the field of microbiology. A field that is at least 200 years old. When we replaced general bacteriology, we found a new species of bacteria within three years. When we tracked an outbreak of C. auris for three years, we discovered novel mutations associated with drug resistance and biofilm formation. Sequencing means that every time you do a diagnosis, you unlock the ability to turn your lab into one with the firepower to do discovery.”
GP: “The most satisfying pattern I’ve seen is in labs who have successfully onboarded sequencing for one purpose, and then an unrelated urgent outbreak situation arises. Suddenly the lab sits at the forefront because leadership wants and needs information that can only be obtained through sequencing the pathogen. Some questions I’ve seen asked are: Was this case imported, or is this pathogen likely circulating in the community? What’s causing the increase in cases this season? In the COVID-19 pandemic, the labs that contributed sequencing data early were the labs that already had sequencing implemented for another purpose. We cannot wait until it’s too late to get things set up, and having routine implementation of sequencing means you will always be ready.”
Q: As public health labs look to expand surveillance genomics, what role can simpler, faster sequencing platforms like the MiSeq i100 play in overcoming adoption barriers?
CREDIT: Illumina
GP: “The MiSeq i100 is easier to adopt because loading it is very user-friendly and eliminates some of the hands-on steps required by earlier models. Additionally, it uses patterned flow cells which are more forgiving about loading concentration. It also has room-temperature reagents, which eliminate the need for large amounts of freezer space. Finally, and most importantly, its kits range from 5M to 100M reads, so it will grow with you as your lab expands sequencing capacity.”
JS: “For pathogen surveillance genomics in PH, speed and accuracy are paramount. By providing highly accurate genomic information in a rapid manner with right-sized run batches, the barriers to adoption have become lower through a reduction in overall costs and execution times.”
MP: “If anyone in the lab can do this quickly, then an interesting barrier disappears. When it is easy, labs don’t fear it because their staff don’t fear learning it.”
Q: What trends are you seeing in how public health laboratories are building sustainable genomics and surveillance programs?
GP: “Typically, I’ve seen labs onboard sequencing programs for one specific project, as that is the project with funding. However, when the results for this project are disseminated and as news travels that your lab has sequencing capabilities, stakeholders begin proposing other ways genomics could be used to answer their questions, and from there, it grows and becomes more sustainable.”
MP: “We can change the narrative of the lab by making sequencing routine for the customer base. In my jurisdiction, and in at least one other, I know that the non-PH labs are looking at their PH lab and saying, “we can’t do what they do.” The path to sustainability is being created. The fundamental rules of American business haven’t changed: you survive, you are sustained, only if you matter. NGS, wielded properly, can make PH labs matter.”
Scott D. Hanton, editorial director for Lab Manager, can be reached at shanton@labmanager.com
