Watchmaker Genomics has introduced TAPS+, an advanced sequencing chemistry that enables simultaneous readout of genetic and epigenetic information from the same DNA molecule. The company describes the platform as a major step toward more comprehensive molecular profiling.
By merging traditionally separate workflows into a single assay, TAPS+ delivers a unified molecular view that could strengthen applications in translational oncology, early cancer detection, therapy monitoring, fragmentomics, and minimal residual disease assessment.
Current gold-standard methylation analysis methods rely on bisulfite conversion, a harsh chemical process that reduces the four-base diversity of DNA to three bases while frequently damaging the template. This degradation can limit sequencing accuracy and complicate variant calling.
TAPS+ introduces a gentler, positive-readout chemistry that specifically converts methylated cytosines (5mC) to thymines, leaving unmethylated cytosines intact. This approach preserves DNA integrity and retains the full four-base sequence complexity, improving base-calling accuracy and enabling direct methylation profiling without destructive conversion steps. According to Watchmaker, the method enhances CpG coverage, maintains sample quality, and reduces false positives.
Leveraging the company’s expertise in enzyme engineering and workflow optimization, the TAPS+ library preparation protocol can be completed in approximately six hours and is compatible with automated liquid-handling systems. This makes it suitable for high-throughput settings and multimodal sequencing pipelines.
Early-access users have reported strong results from pilot studies. Among them, Dr. Matija Snuderl, Director of Molecular Pathology at NYU Langone Health, has applied TAPS+ for combined genomic and epigenomic tumor profiling. Dr. Snuderl is scheduled to present his findings: Integrated Genomic–Epigenetic Profiling of CNS Tumors with TAPS+ for Direct 5mC Detection from ctDNA and FFPE at the Association for Molecular Pathology (AMP) 2025 Annual Meeting on Wednesday, November 12th, at 12 PM ET (Room 153C).
With TAPS+, we can directly detect 5mC alongside genetic drivers, even from difficult samples like FFPE or ctDNA from cerebrospinal fluid. The combination of a unified workflow and improved chemistry delivers the kind of multimodal insight we’ve been waiting for in precision oncology.
Dr. Matija Snuderl, Director of Molecular Pathology at NYU Langone Health
A central aspect of Watchmaker’s design philosophy for TAPS+ is broad platform compatibility. The chemistry has been tested across multiple sequencing systems, including feasibility data presented by Roche at the ASHG 2025 Annual Meeting on an unreleased instrument, and performance validation on Ultima Genomics’ UG 100™.
Unlike some methylation analysis technologies constrained by restrictive licensing, Watchmaker has emphasized an open-access, collaborative approach. The company aims to make TAPS+ widely deployable across research and clinical platforms, supporting applications spanning developmental biology, aging, neuroscience, and cancer genomics.