Including Whole Genome Sequencing Data in Patient Records?

Sept. 13, 2023

Earlier this year, the U.S. Centers for Disease Control and Prevention (CDC) began investigating a multistate outbreak of infections caused by the bacterial pathogen, Listeria monocytogenes, likely tied to the consumption of leafy greens. As an initial step in the investigation, isolates of the bacterium from sick patients were sequenced via whole genome sequencing (WGS); the results aided in the identification of cases caused by the L. monocytogenes outbreak strain to reveal the scope and span of the outbreak.

Though commonly used in epidemiological investigations like this, WGS data are not routinely included in the records of patients from which microbial isolates are, well, isolated—but should they be? Why is including these data important for informing patient diagnosis and treatment? What are the challenges and considerations associated with reporting WGS data as part of standard of care? As the clinical applications and potential of WGS (and next-generation sequencing in general) grow, scientists are debating these questions. 

What is Whole Genome Sequencing and How is it Used?

WGS is exactly what it sounds like: whole genomes, sequenced. It is a form of next-generation sequencing (NGS), in which millions of individual DNA fragments from a sample are processed at a time. WGS is usually conducted using pure, isolated microbial colonies cultured in a lab; the data provide detailed information about the genetic code of microbes, including evolutionary relationships among isolates, which has various clinical and epidemiological indications.   

Whole genome sequencing process from start to finish.
Whole genome sequencing process.
Source: U.S. Centers for Disease Control and Prevention

WGS is used for public health investigations, including the characterization and surveillance of disease outbreaks. It also enables fine-scale identification of bacterial strains (e.g., serotyping Salmonella), and may provide an enhanced ability to identify antimicrobial resistance (AMR) genes and genes associated with virulence and pathogenicity in bacterial isolates, including those from patients.

To that end, while WGS data are collected from patient isolates, traditionally in public health and epidemiological contexts, if and how those data should be included in patient records is an emerging question.  

Why Including WGS Data in Patient Records is Important  

For Esther Babady, Ph.D., D(ABMM), FIDSA, F(AAM), Director of the Clinical Microbiology Service and the CPEP Clinical Microbiology Fellowship program at Memorial Sloan-Kettering Cancer Center, the question of if WGS data should be reported is not much of a question at all. Her stance: “Show me the data.” In other words, if WGS data are available, they must be included in patient records. She offered several reasons why during a debate-style scientific session at ASM Microbe 2023. 

Better Treatment for Patients

3D render of long chains of circular Candida auris cells
Candida auris
Source: BlackJack3D/iStock
“If we get more information on the exact organisms, maybe we can treat and take care of our patients better,” Babady said. She pointed to a recent study examining the antifungal susceptibility of isolates of the fungal pathogen, Candida auris, belonging to 3 different clades circulating in the U.K. While all isolates were resistant to the antifungal drug, fluconazole, the degree of resistance differed depending on the clade to which an isolate belonged. Therefore, determining the clade of their patient’s C. auris isolate via WGS could help clinicians manage an individual patient’s infection more effectively, Babady explained. Indeed, another investigation showed that real-time WGS of SARS-CoV-2 in patient samples allowed scientists to detect persistent infections, evaluate mutations conferring resistance to treatments and, ultimately, guide patient treatment. “Being able to determine [a patient’s SARS-CoV-2] variant in real-time was really useful, especially as the therapeutic choices kept changing,” Babady noted.

It's Already Happening (to an Extent)

Many institutions already offer NGS-based tests (some of which involve WGS) that can be ordered by—and the results reported to—clinicians. Babady emphasized that such tests are performed by labs certified by the Clinical Laboratory Improvement Amendments program (CLIA, the authority on standards for certain laboratory testing), and are thus validated and approved for clinical use. She pointed to an example at the University of Washington, in which clinicians can order a 16S NGS-based test for bacterial detection and receive a curated report in return. Babady also provided additional examples crowdsourced from her clinical microbiology colleagues, including genotyping of bacterial pathogens, bacterial and fungal subspecies identification and more. Thus, reporting of NGS/WGS data, Babady argued, is really nothing new.

Also...The Law

In some ways, Babady stated, the question of “if” WGS data should be included in patient records is a moot one— “it’s kind of the law.” She cited information blocking, a practice specified in the 21st Century Cures Act that prohibits activities by a healthcare professional or provider that are “likely to interfere with access, exchange or use of electronic health information.” Most clinical records, including NGS data and results, are digitized. Therefore, Babady argued, not reporting WGS data from patients could be considered information blocking. “You cannot do anything to prevent the release of information that is relevant to care,” she stated.  

But what exactly is “relevant” to patient care? When it comes to WGS, that might not be clear up front, but having the data ready could be important down the line. If the WGS data are available, “there really isn’t a downside [to reporting them]” Babady said. “If [they’re] useful, great;  if not, [they’re] still there. More information in the right context is always good.”  

The Challenges of Using WGS for Clinical Care

Still, reporting WGS data to inform clinical decisions comes with challenges and considerations that must be taken into account, according to Jocelyn Hauser, Ph.D., D(ABMM), Lab Director in the Department of Forensic Sciences at the District of Columbia Public Health Laboratory. 

Genotype Does not Always Equal Phenotype

Graphic of bacterial cells amidst DNA
Genotype does not always equal phenotype.
Source: kirstypargeter/iStock
Scientists (and clinicians) can learn a lot about microbes from their genomes—but not everything. “We know there are other things besides DNA that influence the actual phenotype [of a microbe],” Hauser said, such as post-translational modifications. Because of this, “using strictly what the nucleotide sequence is can be a challenge and a pitfall [for making] clinical decisions.” For instance, traits like drug resistance and virulence are complex and context-dependent, relying on various physiological and environmental factors. Sequencing may not capture all the nuances needed to accurately infer AMR or virulence phenotypes. For this reason, WGS data may be used in conjunction with other phenotypic tests.

What to Report?

“Another question that needs to be answered is: What do we report?” Hauser said. “Are we reporting the entire genome [of an organism]? Or are we only reporting significant variants [of a pathogen]? What about the variants that are of uncertain significance—do you report those, or do you leave those out?” She emphasized that reports of WGS results necessitate oversimplifying complex data, especially if WGS data are collected from a microbial isolate but only variant data (which may depend on variation in single genetic sequence) are reported. There must be a balance between providing enough information while ensuring it is digestible for the intended audience (i.e., clinicians). 

What Do the Data Mean? 

Data interpretability is also a key consideration. “There’s a need for evidence-based information to be able to guide physicians in treatment and [on how to use] this information,” Hauser said. She asked whether WGS results should simply be presented to a physician, who then determines what the data mean to them? Or is there a need for specialists (e.g., clinical microbiologists working in collaboration with bioinformaticians) for interpretation of the report? Hauser referenced a 2016 study assessing the preparedness of primary care physicians and cardiologists for widespread use of WGS. In general, physicians had concerns about interpreting/responding to WGS data, due, in part, to a lack of guidance on WGS reports, time pressures and a lack of standards.

While this study was not specifically focused on WGS of microbial isolates, Hauser noted similar concerns may apply in a clinical and diagnostic microbiology context. However, scientists are developing strategies for designing alternative reports for WGS data that are more accessible to health practitioners, which may help mitigate some of these concerns. “The format [is something] we can figure out,” Babady stated.

The Bottom Line

WGS is not currently a routine part of clinical or diagnostic microbiology, but, as the applications for NGS expand, it could be. Though traditionally implemented in public health and epidemiological contexts, there is incentive for inclusion of WGS data in patient records. Hauser noted that there are kinks in WGS analyses and reporting that must be ironed out before such reporting becomes standard. For Babady, the time to report is now. “This is how we build the future that we want,” she said, indicating that NGS/WGS data could be integrated into models that advance precision healthcare. “We cannot be scared of the future that we want. [Ultimately], we need to have this information in the same place the rest of the clinical information and metadata is.”
Research in this article was presented at ASM Microbe, the annual meeting of the American Society for Microbiology, held June 15-19, 2023, in Houston. 

How can WGS be used as a surveillance tool in hospitals? Check out this next article to find out.

Author: Madeline Barron, Ph.D.

Madeline Barron, Ph.D.
Madeline Barron, Ph.D. is the Science Communications Specialist at ASM. She obtained her Ph.D. from the University of Michigan in the Department of Microbiology and Immunology.