Host Cell DNA Depletion Prior to Diagnostic Metagenomic Analysis
Application Overview
Pathogen metagenomics enables detection of bacteria, viruses, and fungi directly from clinical or environmental samples—without the need for targeted assays. It can identify rare or unexpected pathogens and provide insights into antimicrobial resistance and virulence, supporting timely and informed treatment.
Recent advances in sequencing, including nanopore-based methods, allow results within hours. Studies show that metagenomics can outperform traditional diagnostics by detecting missed pathogens and offering genomic data that helps guide targeted therapy—especially valuable in time-critical infections.
Application Overview
Pathogen metagenomics enables detection of bacteria, viruses, and fungi directly from clinical or environmental samples—without the need for targeted assays. It can identify rare or unexpected pathogens and provide insights into antimicrobial resistance and virulence, supporting timely and informed treatment.
Recent advances in sequencing, including nanopore-based methods, allow results within hours. Studies show that metagenomics can outperform traditional diagnostics by detecting missed pathogens and offering genomic data that helps guide targeted therapy—especially valuable in time-critical infections.
THE PROBLEM These ENZYMEs SOLVE
To produce reliable and actionable results, metagenomic workflows must effectively enrich microbial nucleic acids from samples dominated by host DNA. Choosing the right tools for host DNA depletion is critical—especially in clinical applications where sensitivity, accuracy, and turnaround time directly impact decision-making.
The table below outlines the primary challenges that effective host DNA depletion strategies must overcome.
These challenges define the performance demands for modern host DNA depletion tools—efficiency, flexibility, specificity, and seamless workflow integration are all essential to unlock the full potential of metagenomic diagnostics.
THE PROBLEM These ENZYME SOLVES
To produce reliable and actionable results, metagenomic workflows must effectively enrich microbial nucleic acids from samples dominated by host DNA. Choosing the right tools for host DNA depletion is critical—especially in clinical applications where sensitivity, accuracy, and turnaround time directly impact decision-making.
The table below outlines the primary challenges that effective host DNA depletion strategies must overcome.
These challenges define the performance demands for modern host DNA depletion tools—efficiency, flexibility, specificity, and seamless workflow integration are all essential to unlock the full potential of metagenomic diagnostics.
THE PROBLEM These ENZYMes SOLVE
To produce reliable and actionable results, metagenomic workflows must effectively enrich microbial nucleic acids from samples dominated by host DNA. Choosing the right tools for host DNA depletion is critical—especially in clinical applications where sensitivity, accuracy, and turnaround time directly impact decision-making.
The table below outlines the primary challenges that effective host DNA depletion strategies must overcome.
These challenges define the performance demands for modern host DNA depletion tools—efficiency, flexibility, specificity, and seamless workflow integration are all essential to unlock the full potential of metagenomic diagnostics.
The Solution
One Toolbox. Many Workflows.
ArcticZymes nucleases offer precise and, efficient solutions for DNA depletion across a range of metagenomic strategies—from rapid, direct-from-sample diagnostics to carefully controlled RNA sequencing protocols.
Efficient removal of host DNA is crucial for unlocking the full potential of pathogen metagenomics—enhancing microbial detection, making the most of limited sequencing depth in rapid workflows, and keeping sample preparation simple. ArcticZymes offers a powerful portfolio of nucleases designed to meet the practical demands of clinical and research labs.
The versatility of this toolbox is demonstrated across a wide range of real-world metagenomic workflows. ArcticZymes’ enzymes have been successfully applied to remove host DNA from diverse sample types—including swabs, stool, blood, respiratory secretions, cerebrospinal fluid, urine, and various food matrices—enabling clear detection of microbial content. These applications highlight the value of a robust and adaptable nuclease portfolio for efficient host DNA depletion, nucleic acid preservation, and support of same-day diagnostic workflows.
The figure below shows enzyme performance across salt conditions typical of clinical samples—from RNA eluates to liquid biopsies and salt-enhanced buffers. Since salt levels directly influence nuclease efficiency, choosing an enzyme suited to your buffer conditions is critical. Mismatched salt compatibility can reduce DNA removal efficiency and compromise overall workflow performance—for example, by lowering assay sensitivity due to sequencing capacity being taken by host DNA.
Figure 1: Enzyme activity across salt concentrations
The reactions are run in a perchloric acid assay, where the transition of high molecular weight DNA to smaller DNA fragments is measured by an increase in light absorbance at A260.
Reactions were incubated for 20 min at 37°C with 0,2 mg/ml Calf Thymus DNA, 5 mM MgCl2, 25 mM Tris-HCl pH 8.0 and various NaCl concentrations.
The reactions were stopped by adding perchloric acid, incubated on ice for 20 min followed by centrifugation. A260 is measured on the sample supernatants and the values are corrected against blank samples (no enzyme control). Note that the HL-dsDNase was run at a different time than SAN HQ and M-SAN HQ.
M-SAN HQ
Peak performance under physiological conditions
Optimized for minimally processed samples like plasma, swabs, or urine, M-SAN HQ depletes host DNA under physiological salt conditions—preserving the integrity of fragile enveloped viruses by avoiding high salt environments that could expose their nucleic acids to unintended nuclease digestion. This enables unified detection of both RNA and DNA pathogens from a single sample without prior purification, supporting sensitive identification across a broad pathogen spectrum. Proven effective in both unified RNA/DNA workflows and DNA-only applications, M-SAN HQ is a highly versatile tool across diagnostic settings.
→ Ideal for: Workflows targeting both viral and bacterial pathogens, including unified DNA/RNA metagenomics and DNA-focused diagnostics
→ Peak activity: Physiological salt levels
→ Strengths: Broad pathogen detection, direct-from-sample use, no need for prior nucleic acid purification.
HL-SAN
Proven performance in salt-boosted protocols
HL-SAN is optimized for use in high-salt environments—where additional salt is added to improve chromatin disruption and accelerate host DNA degradation. This enzyme is especially effective in workflows targeting bacterial pathogens, where speed and robustness are prioritized over sequencing fragile enveloped viruses.
→ Ideal for: Salt-assisted workflows focused on more robust pathogens
→ Peak activity: High-salt conditions
→ Strengths: Optimal at chromatin-disrupting salt levels, direct-from-sample use, no need for prior nucleic acid purification.
HL-dsDNase
Precision DNA removal for RNA-focused applications
In RNA-targeted workflows, HL-dsDNase offers highly specific DNA degradation in low-salt buffers. It’s easily heat-inactivated and integrates smoothly into workflows that involve reverse transcription and downstream RNA virus sequencing.
→ Ideal for: Sample workflows specific for RNA virus detection
→ Peak activity: Low-salt conditions after RNA purification
→ Strengths: High specificity for DNA, RT-compatible inactivation, trusted in traditional metagenomic pipelines
Quality
ArcticZymes’ nucleases are engineered to meet the real-world demands of pathogen metagenomics where assay sensitivity, workflow speed, and sample complexity all play a role. Their performance is rooted in precise salt compatibility, ensuring each enzyme functions optimally in the sample conditions it was designed for. From enabling same-day diagnostics to supporting full-spectrum pathogen detection, our enzyme toolbox offers the reliability and flexibility needed to overcome the practical barriers of host DNA depletion.
All our enzymes are manufactured under ISO 13485 certification, giving you the assurance of consistent quality and clinical readiness.
Relevant Publications
Unified Metagenomic Method for Rapid Detection of Microorganisms
Published in Communications Medicine, this study validates HL-SAN in a same-day metagenomic workflow combining mechanical and enzymatic depletion to detect bacteria, fungi, and viruses from respiratory samples.
🔗 Read the article
Pan-Microbial Metagenomics Protocol v1.2
This protocol outlines a clinically applicable workflow using M-SAN HQ for pathogen detection in liquid samples under physiological conditions. It supports simultaneous identification of bacteria, viruses, and fungi while preserving both DNA and RNA. Presented as an improved workflow to the publication above.
🔗 Access the protocol
Nanopore Metagenomics Enables Rapid Clinical Diagnosis of Bacterial Lower Respiratory Infection
A landmark Nature Biotechnology publication highlighting HL-SAN in a metagenomic pipeline used for same-day pathogen identification from respiratory samples, paving the way for clinical adoption.
🔗 Read the article
Development of a Clinical Metagenomics Workflow for the Diagnosis of Wound Infections
Published in BMC Medical Genomics, this study demonstrates the use of HL-SAN for host DNA depletion from wound swab samples in a clinical metagenomics setting.
🔗 Read the article
Capturing Clinically Relevant Campylobacter Attributes Through Direct Whole Genome Sequencing of Stool
This study applies HL-SAN to stool samples for effective DNA enrichment and recovery of Campylobacter genomes.
🔗 Read the article
Deep Longitudinal Lower Respiratory Tract Microbiome Profiling Reveals Genome-Resolved Functional and Evolutionary Dynamics in Critical Illness
Published in Nature Communications, this paper uses HL-SAN in metagenomic profiling of lower respiratory tract samples from intubated patients.
🔗 Read the article
Development and Proof-of-Concept Demonstration of a Clinical Metagenomics Method for the Rapid Detection of Bloodstream Infection
This BMC Medical Genomics article describes the use of HL-SAN in blood-based metagenomic workflows to enhance microbial signal by removing host DNA.
🔗 Read the article
A New and Efficient Enrichment Method for Metagenomic Sequencing of Monkeypox Virus
This study highlights HL-SAN’s use in vesicular fluid samples, improving detection of monkeypox virus in clinical material.
🔗 Read the article
Determination and Quantification of Microbial Communities and Antimicrobial Resistance on Food Through Host DNA-Depleted Metagenomics
Published in Food Microbiology, this paper showcases HL-SAN for host depletion in food matrices including meat, seafood, and produce, enabling metagenomic detection of microbes and resistance markers.
🔗 Read the article
SARS-CoV-2 Genotyping and Sequencing Using Simple RNA Prep
This PLOS ONE study supports the use of HL-dsDNase in RNA virus workflows, showing that DNA removal prior to cDNA synthesis improves genome completeness and sequencing quality from low-input samples.
🔗 Read the full article
Application Background
A subsequent DNase (HL-SAN) treatment of previously lysed eukaryotic cells remarkably decreases the host DNA present in the samples.
BMC Genomics 2023 24:29