4 Strategies for Reducing mNGS Costs Per Sample
Reducing mNGS costs is the single largest barrier standing between metagenomic next-generation sequencing (mNGS) and its routine use in clinical diagnostics. Per-sample costs remain high enough to limit mNGS to reference laboratories and well-funded research programs, even though the technology offers unbiased pathogen detection, antimicrobial resistance (AMR) profiling, and identification of novel organisms. In a recent Micronbrane Medical micro-webinar, Hannah Lucio presented four concrete strategies that laboratories can implement to cut costs while simultaneously improving the proportion of microbial reads in their sequencing data.
Key Takeaways
- Host DNA interference is the primary cost driver in mNGS, inflating sequencing depth requirements and downstream analysis time
- Effective pre-sequencing host depletion can reduce human reads by approximately 99%, dramatically improving microbial read fraction
- Reagent contamination introduces false positives that trigger expensive retesting and validation cycles
- Optimized library preparation kits designed for ultra-low biomass inputs (as little as 10 picograms) prevent failed preps and wasted reagents
- Purpose-built bioinformatics pipelines reduce computational cost and eliminate database-contamination artifacts
Where mNGS Costs Accumulate
Every step in the mNGS workflow carries a cost component, but the financial impact is not evenly distributed. The webinar broke down how host interference, reagent quality, library construction failures, and bioinformatics complexity each contribute to the total per-sample cost.
Pre-Sequencing Host Depletion
Enzymatic digestion methods require costly reagents and sometimes specialized equipment. They are labor-intensive manual processes that increase hands-on time, labor costs, and contamination risk. Differential lysis selectively breaks open host cells while preserving microbial cells, but requires longer processing times and can lack consistency across microbial species with varying sensitivity to lysis conditions.
Post-Sequencing Host Removal
Without pre-sequencing depletion, laboratories must sequence deeper to capture enough microbial signal. This drives up reagent costs for sequencing, demands more data storage, and increases the computational intensity of bioinformatics analysis. The deeper you sequence to compensate for host reads, the more you pay at every downstream step.
Effective Host Depletion Drives Down Sequencing Spend
The webinar presented data comparing three host depletion methods head-to-head: the Devin filter, human methylated DNA removal, and differential lysis.
The Devin Host Depletion Filter uses Micronbrane Medical’s Zwitterionic membrane technology to remove nucleated cells from liquid biopsies in under five minutes. In published data, the Devin filter depleted approximately 99% of host DNA while maintaining high microbial passing efficiency. The filter is compatible with all liquid biopsy types and supports sample volumes from 50 microliters to 10 milliliters.
By contrast, human methylated DNA removal targets methylated patterns to deplete host DNA but can miss unmethylated regions, leaving residual host contamination that reduces the effective microbial read fraction. Differential lysis preserves microbial cells but requires longer processing times and can cause loss of certain microbial species that are sensitive to lysis conditions.
In qPCR validation, the Devin filter showed increased cycle threshold (CT) values for human DNA (indicating reduced host DNA), while CT values for microbial DNA remained unchanged, confirming that microbial recovery was not compromised during host removal.
Why mNGS-Grade Reagents Prevent Costly Retesting
Reagent contamination is an underappreciated cost multiplier. Contaminants in extraction reagents introduce background nucleic acids that lead to pathogen misidentification, particularly among closely related species. Each misidentification triggers retesting and validation cycles that increase turnaround time and cost.
The Devin Microbial Enrichment Kit addresses this with mNGS-grade reagents manufactured under strict quality control. The kit extracts DNA from both gram-negative and gram-positive bacteria, works with manual and automated workflows, and includes a certificate of analysis (COA) with each batch for traceability during analysis.
Specialized Library Prep for Low-Biomass Samples
Failed library constructions are among the most expensive events in an mNGS workflow. Each failure wastes reagents, requires extra sequencing runs, and increases labor and troubleshooting time.
The Unison Ultra Low Library Kit is optimized specifically for host-depleted samples, requiring only 10 picograms of DNA input. This is critical for sample types with limited DNA, such as cerebrospinal fluid (CSF). The kit has a hands-on time of 45 minutes and a total processing time of 150 minutes. For high-biomass samples, the Unison includes a normalizing function that saves additional time while optimizing throughput and data quality.
Combined with PaRTI-Seq analysis, this workflow can identify pathogens with as few as 5 million reads, enabling laboratories to process four times more samples per sequencing run compared to traditional methods. PaRTI-Seq produces 10 to 1,000 times more microbial reads, enhancing both resolution and accuracy of pathogen detection.
High-Fidelity Bioinformatics to Avoid Misidentification
Database contamination in mNGS can lead to trimming errors, poor-quality reads, and species misidentifications that require corrections and additional testing. Updating reference genomes demands significant computational resources, and data mismanagement due to contamination requires recovery and reanalysis.
PaRTI-Seq Analysis mitigates these challenges with a curated database of over 1,400 pathogens, purpose-built to reduce genome misclassification. The platform eliminates the need for bioinformatics expertise: users upload data, run the analysis, and download results. The software is free for research use only (RUO) groups.
How Micronbrane Medical Products Optimize the Full Workflow
The four strategies presented in the webinar map directly to Micronbrane Medical’s product line: host depletion with the Devin filter, contamination-free extraction with mNGS-grade reagents, reliable library construction with the Unison Ultra Low Library Kit, and accurate pathogen identification with PaRTI-Seq Analysis. Together, these products address cost at every stage of the mNGS workflow, from sample processing through final reporting.
For teams reducing per-sample sequencing spend, the most direct product path is to combine the Devin Host Depletion Filter, Devin Microbial DNA Enrichment Kit, Unison Ultralow Library Preparation Kit, and PaRTI-Seq Analysis into a single mNGS workflow.
About the Speaker
Hannah Lucio is the Global Commercial Lead at Micronbrane Medical. Prior to Micronbrane, she led partnerships and product development at Oxford Nanopore Technologies, served as Clinical Transplant Lead at Natera, and held commercial roles at Thermo Fisher Scientific, Agilent, and Life Technologies. She began her career as a microbiologist at the Texas Department of State Health Services and the Centers for Disease Control and Prevention.
