Genomic Identification and Surveillance

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Sequencing: Genomic Surveillance & Bioinformatics

Over the recent years, the Delaware Public Health Laboratory (DPHL) has made significant strides in harnessing genomics to improve public health laboratory’s abilities to improve outbreak surveillance. Specifically with SARS-CoV-2 during the Covid-19 Pandemic, DPHL were able to greatly expand genomic capabilities to interpret the genetic makeup for the context of pandemic surveillance, variant evolution, and outbreak clustering within Delaware. The Sequencing Section, supported by a diverse array of funding has strategically invested in advanced technology, acquiring next-generation sequencing (NGS) instruments, including short-and long-read technology, and automated liquid handling/robotics for comprehensive laboratory testing, ushering in a new phase of genomic surveillance/detection.

Our methodology revolves around whole genome sequencing (WGS), a process that involves deciphering the individual letters of a pathogen’s entire genetic code, or genome, translating them into "raw" data files. These files necessitate sophisticated computational tools and software for translation into usable data, a field known as bioinformatics. The meticulously analyzed data is shared with state and national partners to enhance public health response, providing detection of known and unknown agents, epidemiological surveillance, monitoring of antimicrobial resistance (AMR), outbreak investigation, and more.

Initial implementation of technologies with the Centers for Disease Control and Prevention (CDC) involved testing and analysis through use of their foodborne outbreak databases, PulseNet and CaliciNet. This collaborative effort empowers DPHL and the Office of Infectious Disease Epidemiology (OIDE) to investigate and determine foodborne outbreaks in real time.

At present, DPHL extensively employs WGS and targeted sequencing for the surveillance of various foodborne pathogens, including but not limited to:

Salmonella species
Shigella species
Shiga toxin producing E. coli (STEC)
Listeria monocytogenes
Campylobacter species
Vibrio species
Norovirus

The Sequencing Section employs whole genome sequencing for identification of fastidious and atypical bacteria, particularly for pathogens that are similar in morphology, where identification with traditional methods has been difficult. This technique not only improves identification of these agents, but also linking them to potential outbreaks. Additionally, this contributes to emergency preparedness when ruling out any suspected biothreat agents. The Section has effectively utilized this technology to support the identification of novel pathogens, leading to a noteworthy publication in the CDC’s Emerging Infectious Disease (EID) Journal in October 2018. Emerging Infectious Diseases — (CDC)

Beyond its application in identifying atypical pathogens, DPHL utilizes the power of Whole Genome Sequencing (WGS) for proactive surveillance of SARS-CoV-2 outbreaks in Delaware. This advanced technology has not only enabled the identification of SARS-CoV-2 variants, such as the Delta and Omicron, but also continuous monitoring of emerging variants of concern. DPHL can interpret, based on their evolutionary changes with virulence factors, if potential threats are evolving at a local level.

The Sequencing section at DPHL is at the forefront of leveraging Next-Generation Sequencing (NGS) equipment and bioinformatics to enhance the identification of various infectious diseases, a crucial aspect of the Advanced Molecular Detection (AMD) and Response to Infectious Disease Outbreaks (CDC.gov), a CDC initiative to enhance these technologies at the national level. In addition to SARS-CoV-2 sequencing, we have methods to detect and monitor multiple public health pathogens. Specifically for viruses, DPHL has implemented test methods for Hepatitis C Virus (HCV) and Influenza Virus types A and B.

Influenza A and B sequencing is of particular significance, serving as a crucial tool in identifying subtypes and lineages, including those that may be deemed as biothreat (avian influenza). As we delve into the sequencing of various viruses, decoding the genotype of Hepatitis C (HCV), play a pivotal role. The replication rate of HCV underscores the importance of genetic sequencing as evolutionary changes to the virus make it a difficult task to construct phylogenetic relatedness. Further, genetic sequencing allows for the identification of antiviral resistance in both viruses, ensuring appropriate therapeutic intervention be initiated or use of alternative diagnostic treatments.

DPHL remains committed to expanding NGS activities, expanding our capabilities to support surveillance activities of multi-drug resistant organisms (MDRO) associated with hospital-acquired infections (HAI). HAI are a considerable drain on the healthcare system, and identifying novel solutions to prevent spread of nosocomial infections enables the ongoing commitment to use this technology in our mission to combat infectious diseases and safeguard public health. As a member of the (AR Lab Network | CDC), DPHL partners with state, regional, and national partners to identify potential clusters of MDRO, identify novel MDRO, and coordinate with DPH partners to initiate infection prevention strategies to limit the spread of MDRO.

In efforts to enhance DPHL’s sequencing capabilities, the Sequencing Section collaborates closely with DPHL’s Wastewater Section and Informatics Section. This collaboration aims to bolster the ability to provide predictive modeling for spread of infectious diseases. Currently DPHL focus with respiratory viruses (SARS-CoV-2, influenza virus A/B, and Respiratory Syncytial Virus (RSV)) through collaboration with the CDC’s National Wastewater Surveillance System (NWSS). The surveillance of respiratory viruses in wastewater serves as an early warning system, offering insights into the virus’s presence in our communities.

Below is a breakdown of the process and its significance:

Genetic Analysis Platforms: These platforms likely include various technologies and instruments designed to analyze genetic material. They could involve PCR (Polymerase Chain Reaction), microarray analysis, next-generation sequencing (NGS) instruments, and other advanced molecular biology tools.
Whole Genome Sequencing (WGS): This technique involves determining the complete DNA sequence of an organism's genome. In the context of identifying pathogens causing outbreaks, WGS allows for precise identification and comparison of genetic sequences, aiding in understanding the origin, spread, and evolution of these pathogens.
Surveillance and Outbreak Detection: By utilizing WGS, the Sequencing and Bioinformatics section can detect potential pathogens swiftly and accurately. This helps in early identification of outbreaks, allowing for timely response and intervention.
Epidemiological Investigation: The genomic data generated through WGS assists epidemiologists in conducting contact tracing on a national level. This involves tracking and identifying individuals who may have been exposed to the pathogen, helping to contain the spread.
Assessment of Community Spread: WGS data analysis also aids in understanding the dynamics of the spread within specific settings such as schools, colleges, and hospitals. This information is crucial for implementing targeted interventions to mitigate further transmission.
Public Health Implications: This approach is highly beneficial for public health as it enables a more precise and rapid response to outbreaks, thereby potentially reducing the impact on communities and preventing larger-scale public health crises.

Bioinformatics

At the DPHL, the team of bioinformaticists plays a pivotal role in advancing public health through their expertise in analyzing the vast amount of data generated through genomic sequencing. Leveraging various cutting-edge workflows and sophisticated pipelines, these experts meticulously sift through the genomic data obtained from diverse sources, including pathogens and disease samples, to report an accurate depiction of the pathogen’s genomic structure, including virulence and antimicrobial resistance markers, and the relationship to related pathogens, inferring and association through an outbreak setting.

One of the primary areas of focus for DPHL’s bioinformaticists is sharing the sequencing data with state epidemiologists to perform disease transmission analysis. By carefully studying the genomic sequences of pathogens, epidemiologists can trace the routes of transmission, helping to identify the sources of outbreaks and understand how diseases spread within communities. This information is vital for crafting effective containment strategies and implementing timely interventions to prevent further spread.

Additionally, the team utilizes cluster detection, a process that involves identifying clusters of closely related pathogens with genetic variations within a specific population. The CDC and other state and federal partners (NIH) provide resources to enable DPHL to predict potential outbreak clusters with platforms, through software or web-based, which can be shared with epidemiologists in real-time to, assist in preventing the spread of outbreaks.

Further, proficiency in identifying antimicrobial resistance genes is crucial in combating the growing concern of drug-resistant pathogens. By pinpointing the genetic markers responsible for resistance, bioinformaticists notify public health authorities to devise treatment protocols and strategies to mitigate the risk of widespread antimicrobial resistance.

Once the team of bioinformaticists process and analyze the genomic data, they collaborate closely with epidemiologists to translate their findings into actionable insights. These insights serve as a foundation for the epidemiologists to make critical decisions regarding public health measures, outbreak responses, and allocation of resources and medical interventions throughout the state of Delaware.

In the spirit of open science and knowledge sharing, DPHL follows federal strategies by sharing deidentified data to widely used national public databases, such as the National Center for Biotechnology Information (nih.gov) and the Home - SRS- NCBI (nih.gov). By doing so, they enhance collaboration with other research institutions and allow the global scientific community to access and build upon their findings, fostering a collective effort to combat public health challenges on a broader scale.

Overall, the collaborative efforts between the bioinformaticists, genomic sequencing scientists, and epidemiologists at DPHL showcase how cutting-edge data analysis and sharing practices are fundamental pillars in safeguarding public health in Delaware and beyond.

For additional information and a list of DPHL partners:

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This page was last update 4/24

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Genomic Identification and Surveillance

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