Applications | Future Development

Infectious Disease

Explore circulating microbial nucleic acids as an emerging molecular signal in infectious disease research.

STATUS Future Development
SAMPLE Plasma + Biofluids
SIGNAL Microbial Nucleic Acids
Applications cfDNA cfRNA | cfTNA Urine Preanalytical Urine CTC Exosomes Infectious Disease
INFECTIOUS DISEASE RESEARCH

Pathogen-derived molecular signals can circulate within a complex host background.

During infection, microbial nucleic acids can enter circulation alongside abundant host-derived DNA and other biological material. Plasma microbial cell-free DNA (mcfDNA) is being investigated as a source of pathogen-associated molecular information.1–3

Metagenomic sequencing approaches have demonstrated the ability to detect circulating DNA derived from multiple classes of microorganisms, including bacteria, DNA viruses, fungi, and eukaryotic parasites.1

Because microbial signal may represent only a small fraction of the nucleic-acid background in a biological sample, upstream sample preparation remains an important consideration when developing molecular infectious-disease research workflows.

01 Microbial cfDNA

Pathogen-derived cell-free DNA can circulate in plasma and provide molecular material for downstream research.

02 Complex Background

Microbial nucleic acids may coexist with a much larger background of host-derived molecular material.

03 Molecular Analysis

Recovered nucleic acids can be carried into sequencing and other downstream molecular research workflows.

MOLECULAR SIGNAL

A rare microbial signal within a much larger biological background.

In plasma, microbial cfDNA can represent only a fraction of the total circulating DNA available for analysis.

The analytical challenge is therefore not simply the presence of nucleic acid. It is preserving and recovering sufficient pathogen-associated material from a complex sample before downstream molecular analysis begins.

UPSTREAM MATTERS Molecular information that does not reach the downstream workflow cannot contribute to the analysis.
MIXED MOLECULAR BACKGROUND Host-derived material + microbial signal
LOW-ABUNDANCE SIGNAL Microbial cfDNA
Host Background
Microbial Signal
THE UPSTREAM CHALLENGE

Low-abundance molecular signals still have to be recovered.

Downstream molecular analysis begins with material that successfully survives sample collection, handling, extraction, and preparation. When microbial nucleic acids are present at low abundance, upstream losses can reduce the material available for characterization.

As infectious-disease molecular workflows evolve, preanalytical recovery may be an important variable in determining the molecular starting material presented to downstream technologies.

THE ASSAY BEFORE THE ASSAY What reaches the molecular workflow defines what is available to be measured.
01
BIOLOGICAL SAMPLE Collect
02
NUCLEIC ACIDS Recover
03
MICROBIAL SIGNAL Analyze
RESEARCH LANDSCAPE

Microbial cfDNA spans multiple pathogen classes.

Plasma microbial cell-free DNA sequencing has been investigated across diverse microorganism classes and clinical research settings.1–3

01
MICROBIAL DNA

Bacteria

Investigate circulating bacterial DNA within plasma and other molecular infectious-disease research workflows.

02
VIRAL DNA

DNA Viruses

Microbial cfDNA sequencing approaches can include circulating DNA derived from clinically relevant DNA viruses.

03
FUNGAL DNA

Fungi

Plasma pathogen cfDNA has been investigated in research involving invasive fungal infections.2

04
BROAD DETECTION

Other Pathogens

Metagenomic mcfDNA approaches have also been evaluated for eukaryotic parasites and other microbial organisms.1

MOLECULAR WORKFLOW

From biological sample to microbial investigation.

Sample preparation sits between the biological specimen and the molecular technology used to investigate the microbial signal.

01
START Sample

Plasma or another biological fluid

02
UPSTREAM Recover

Isolate circulating nucleic acids

03
DOWNSTREAM Analyze

Apply molecular analysis or sequencing

04
RESEARCH Investigate

Evaluate pathogen-associated signals

FUTURE DEVELOPMENT

Evaluating where recovery-focused sample preparation may support infectious disease research.

Infectious-disease molecular workflows can involve low-abundance microbial signals within complex biological backgrounds.

nRichDX continues to evaluate emerging molecular applications where sample preparation and nucleic-acid recovery may provide value. No infectious disease-specific nRichDX diagnostic product is currently available.

01 SAMPLE Complex Biofluids
02 RECOVERY Nucleic Acids
03 ANALYSIS Molecular Signal
Explore Established Solutions Discuss Research Workflows
SCIENTIFIC CONTEXT

Explore the broader nRichDX molecular sample-preparation resource library.

Review scientific posters, application data, and technical resources across established nRichDX liquid biopsy and molecular sample-preparation workflows.

Molecular Recovery Sample Preparation Posters & Publications
View Reference Materials Contact nRichDX
REFERENCES

Literature cited

  1. Blauwkamp TA, et al. “Analytical and Clinical Validation of a Microbial Cell-Free DNA Sequencing Test for Infectious Disease.” Nature Microbiology. 2019;4(4):663–674.
  2. Hong DK, et al. “Liquid Biopsy for Infectious Diseases: Sequencing of Cell-Free Plasma to Detect Pathogen DNA in Patients with Invasive Fungal Disease.” Diagnostic Microbiology and Infectious Disease. 2018;92(3):210–213.
  3. Jing C, et al. “Plasma Cell-Free Metagenomic Next-Generation Sequencing in the Clinical Setting for the Diagnosis of Infectious Diseases: A Systematic Review and Meta-Analysis.” Journal of Clinical Microbiology. 2023;61(1):e01105-22.