Researchers Developed New Plasmid Sequencing Protocol
The PICARD-seq method improves DNA accuracy by resolving repeated parts that often elude short-read sequencing approaches.
Updated on Sept. 24, 2026 in Life Sciences
Researchers have developed PICARD-seq, a new sequencing protocol designed to identify errors in laboratory-made plasmids. Approximately one-third of these synthetic genetic constructs currently contain sequence errors, a challenge that conventional Sanger and short-read methods struggle to resolve.
Why it matters
The PICARD-seq protocol addresses limitations in scaling and resolution for synthetic DNA assembly. By enabling precise identification of backbone concatemers and misincorporated parts, this method improves quality control in biological research.
PICARD-seq utilizes Tn5 rapid barcoding reagents and MinION sequencing to process plasmids between 3.0 and 20.6 kbp. Processing times for the ONT EPI2ME workflow ranged from 13 to 18 minutes, while the Autocycler assembler required 81 to 111 minutes.
The players
Oxford Nanopore Technologies
A developer of nanopore-based DNA and RNA sequencing systems, including the MinION and the EPI2ME workflow used for clone validation.
The details
The protocol uses off-the-shelf Tn5 rapid barcoding reagents—enzymes that fragment and tag DNA for sequencing—to handle pools of whole plasmids. Researchers then perform read mapping with minimap2, an alignment tool, to distinguish sequence differences from assembly artefacts. Reducing minimum coverage requirements from 60x to 20x was found to improve the assembly of large, repetitive DNA sequences.
Timeline
September 24, 2026: The research results were published.
The Tech Race
PICARD-seq marks a shift away from the labor-intensive Sanger sequencing method, which struggles with the resolution of repetitive DNA parts. This development positions nanopore-based pipelines as the primary path for rapid, high-throughput genetic validation.
Researchers can adopt this protocol to reduce the time spent on plasmid verification using existing MinION hardware. The method enables faster screening of genetic samples by optimizing coverage parameters to resolve complex, repetitive sequence assemblies.
The takeaway
PICARD-seq provides a faster alternative for validating laboratory-made plasmids by reducing coverage requirements while maintaining assembly precision. Researchers should monitor future benchmarking results to see if the 20x coverage optimization maintains similar reliability across more complex, synthetic genome architectures.
Further reading
For more developments in genomic research, visit the Life Sciences section.
Source note: This article includes information reported by Biorxiv.
