Watchmaker DNA Library Prep Kit with TAPS+
The power of positive.
Traditional methyl-seq converts every unmethylated cytosine to thymine, collapsing the genome's four-letter alphabet (A, T, C, G) to three — and bisulfite does it by chemically battering the DNA, leaving coverage gaps and ruling out fragile or low-mass samples. The Watchmaker DNA Library Prep Kit with TAPS+ inverts that logic. It is a positive-readout chemistry: it converts only the methylated cytosines (5mC and 5hmC) to a thymine signal and leaves unmethylated cytosines untouched, so the native four-base complexity is preserved.
One library, multimodal answers.
Because base diversity survives, a single TAPS+ library reports methylation and genetic variation — 5mC, SNVs/indels and copy-number changes — without the alignment penalties, mappability dropouts and phiX spike-ins that dog bisulfite and enzymatic methyl-seq. That makes it a natural fit for multi-cancer early detection, minimal residual disease, tumour profiling and population-scale epigenomics.
Gentle, fast and automatable.
The non-damaging chemistry preserves DNA integrity and library complexity from challenging, clinically relevant material — FFPE, fresh-frozen tissue, blood and cell-free DNA — across a 1–200 ng input range, including inputs as low as 1 ng. The streamlined, column-free workflow produces libraries in under six hours and translates cleanly to liquid handlers, while the preserved base diversity cuts downstream computational analysis time by 30% or more on a 30× genome.
- Direct 5mC readout: > 98% 5mC conversion with low (≤ 0.3%) false-positive rates.
- Multimodal from one library: methylation, SNV/indel and CNV calling without a separate run.
- Built on a proven base: an engineered TET enzyme, novel borane reagent and a DHU-tolerant amplification module refine the original TAPS chemistry for real-world samples.
For Research Use Only. Not for use in diagnostic procedures.
| Parameter | Specification |
| Input range | 1 – 200 ng of DNA (including cfDNA and FFPE) |
| Readout | Positive 5mC/5hmC → T conversion; unmethylated C preserved (four-base complexity retained) |
| 5mC conversion | > 98% (hypo- and hyper-methylated regions) |
| False-positive rate | ≤ 0.3% with commercially available controls |
| Multimodal output | Methylation (5mC) + SNV/Indel + CNV from a single library |
| Turnaround time | < 6 hours; column-free, automation-friendly |
| Key modules | DNA Library Prep (PCR-free) module + TAPS+ Methyl-seq module + Equinox® DHU-Tolerant amplification |
| Sample compatibility | cfDNA, blood, cell lines, fresh-frozen tissue, FFPE |
| Sequencing platforms | Illumina, Ultima, Element, Complete Genomics / MGI (T/A ligation, unmethylated adapters) |
| SPRI beads | AMPure XP required |
| phiX | Not required (base diversity preserved) |
| Shipping conditions | Ice packs or dry ice |
| Storage | −20 °C ± 5 °C |
| Shelf life | 24-rxn: ≥ 6 months · 96-rxn: ≥ 6 months |
| Quality system | Manufactured under ISO 13485:2016 |
| Article Number | Description | Reactions |
| 7BK0003-024 | Watchmaker DNA Library Prep Kit with TAPS+ — incl. reagents for DNA library prep, TAPS+ conversion and amplification | 24 rxn |
| 7BK0003-096 | Watchmaker DNA Library Prep Kit with TAPS+ — incl. reagents for DNA library prep, TAPS+ conversion and amplification | 96 rxn |
| No 384-rxn format listed. Custom configurations available on request. | ||
| Topic | Detail |
| Modifications detected | 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) in CpG context |
| Adapters | Unmethylated adapters required; T/A ligation; stubby or Full-Length UDI; UMI-compatible; "Y" adapters best preserve strand info |
| Controls | Contact Watchmaker for commercial conversion / false-positive controls |
| Analysis tools | TAPS+ Variant Caller; nf-core/methylseq TAPS branch (in review); DRAGEN Methylation pipeline with TAPS enabled (Illumina BaseSpace) |
| Safe stopping points | After ligation, oxidation and reduction clean-ups (see User Guide) |
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Tell us your sample type, input amounts and platform, and we'll help you select and validate the right DNA chemistry — with evaluation samples, automation scripts and local logistics.
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Multimodal genomic and epigenomic profiling, from discovery to the clinic-research bench
Multi-cancer early detection (MCED)
Sensitive methylation signatures plus variant calls from low-input cfDNA support MCED assay development.
Minimal residual disease (MRD)
High CpG coverage and preserved fragments enable sensitive monitoring from liquid biopsy.
Tumour profiling (incl. FFPE)
Methylation and genomic variation from the same archival sample — gentle enough for degraded FFPE.
Methyl-seq, WGBS & targeted
A bisulfite-free alternative for whole-genome or targeted methylation sequencing, including EPIC-array use cases.
Differential & allele-specific methylation
Reproducible profiles resolve DMRs and allele-specific methylation in tumour/normal comparisons.
Population & EWAS, fragmentomics, ageing
Scalable, automation-friendly chemistry for epigenome-wide association, fragmentomic and ageing studies.
A single-day, column-free workflow
Library, conversion and amplification — under six hours, automation-ready
1. Library prep
ER/AT and ligation build a standard, UMI-compatible library from 1–200 ng of DNA using unmethylated adapters.
2. Oxidise
An engineered TET enzyme oxidises 5mC/5hmC — the gentle, non-damaging first step of positive conversion.
3. Reduce
A novel borane reagent completes conversion to a T signal, with safe stopping points after each clean-up.
4. Amplify & sequence
Equinox® DHU-Tolerant master mix amplifies with low GC bias; sequence on Illumina, Ultima, Element or MGI — no phiX required.
- DIRECT 5mC SEQUENCING
- NO BISULFITE
- METHYLATION + SNV/INDEL + CNV FROM ONE LIBRARY
- >98% 5mC CONVERSION
- FFPE & cfDNA FROM 1 ng
- LIBRARIES IN UNDER 6 HOURS
- NO CONVERSION COLUMNS
- DIRECT 5mC SEQUENCING
- NO BISULFITE
- METHYLATION + SNV/INDEL + CNV FROM ONE LIBRARY
- >98% 5mC CONVERSION
- FFPE & cfDNA FROM 1 ng
- LIBRARIES IN UNDER 6 HOURS
- NO CONVERSION COLUMNS
The power of positive: a five-base genome
Preserve A, T, C, G — and read 5mC as the fifth base
Only ~1–2% of human cytosines sit in the CpG context where most methylation occurs. TAPS+ converts just those methylated CpG cytosines and leaves the rest untouched, so the library keeps its native four-base composition and reads more like the reference genome — while still delivering a direct 5mC signal. The payoff is practical: better alignment and QC, fewer low-complexity dropouts, no costly methylated adapters, reduced need for phiX spike-ins, and SNV/indel and CNV calling alongside methylation from the same library.
Accurate methylation, minimal false positives
> 98% conversion, ≤ 0.3% false positives
By preserving native four-base diversity, TAPS+ improves mapping and QC while delivering high-efficiency 5mC conversion (> 98%) across both hypo- and hyper-methylated regions, with minimal false positives. In head-to-head testing against enzymatic and bisulfite methyl-seq, it matched methylation accuracy while keeping false-positive rates low — the foundation for trustworthy differential-methylation calls.
Methylation and variants from a single library
SNV/indel and CNV calling on par with an unconverted control
Most methyl-seq forces a choice: profile methylation, or genotype — but not both from one library. Because TAPS+ preserves four-base complexity and native coverage, SNV and CNV calls hold up against an unconverted whole-genome control. One TAPS+ library therefore supports integrated methylation and variant analysis, halving the sample and sequencing burden for multimodal studies.
Positive readout vs enzymatic and bisulfite methyl-seq
How TAPS+ compares
vs Bisulfite
Bisulfite chemically damages DNA and collapses base diversity, causing coverage gaps and sample limitations. TAPS+ is non-damaging and preserves complexity.
vs EM-Seq (enzymatic)
Enzymatic methyl-seq also reduces base diversity and genomic-variant fidelity. TAPS+ retains both, with lower false positives — especially on FFPE.
TAPS+ advantage
High methylation accuracy, low false positives, native base diversity, genomic-variant detection, non-damaging chemistry, automatable workflow, and reduced compute.
Choose the right Watchmaker DNA chemistry
Three DNA chemistries — matched to your sample and question
DNA Library Prep with TAPS+
Direct 5mC methyl-seq plus SNV/Indel/CNV from one library; gentle, bisulfite-free chemistry for FFPE and cfDNA (1–200 ng).
DNA Library Prep Kit (Standard)
For pre-fragmented inputs — cfDNA, sonicated or enzymatically sheared DNA. Maximum conversion for liquid biopsy and low-frequency variants.
DNA Library Prep with Fragmentation
For intact genomic DNA. Tunable enzymatic shearing (<1 ng–500 ng), up to 90% fewer artefacts, PCR-free libraries in <90 min.
COMPLETE YOUR NGS PIPELINE
Tailored Solutions for Challenging Applications
A great result relies on more than just a single high-quality reagent. Visit our Solutions page to see how we integrate cutting-edge technologies, like Watchmaker Genomics, into end-to-end workflows designed to maximize your laboratory’s efficiency and sequencing yield.
Technical insights & kit selection
Practical guidance on TAPS+ chemistry, samples, sequencing and analysis.
Traditional methods convert unmethylated C→T, reducing base diversity and (for bisulfite) damaging DNA. TAPS+ is a positive readout: it directly converts methylated C (5mC) to a T signal and leaves unmethylated C intact, minimising damage and preserving library and sequence complexity.
Methylated CpG cytosines — 5mC and 5hmC — are read out as a T signal; unmethylated CpG cytosines remain C.
1–200 ng of DNA, including cfDNA and DNA from blood, cell lines, fresh-frozen tissue and FFPE.
Typically > 98% conversion of 5mC/5hmC with low (≤ 0.3%) false positives using commercially available controls; rates can vary by sample type. Contact us for recommended controls.
Yes. Because base diversity is preserved, a single TAPS+ library supports SNV/indel and CNV calling on par with an unconverted control, alongside methylation.
TAPS+ adds an optimised library-prep module for better conversion (especially low input), an engineered TET enzyme, a novel borane reagent and a DHU-tolerant amplification module — refined for real-world samples and automation.
A TAPS+ Variant Caller, a TAPS+ branch of nf-core/methylseq (in review), and the DRAGEN Methylation pipeline with TAPS enabled in Illumina BaseSpace. See the TAPS+ Data Analysis Guide.
Unmethylated adapters with a T/A ligation scheme — stubby or Full-Length UDI, UMI-compatible. Compatible with Illumina, Ultima, Element and Complete Genomics/MGI. PhiX is not required because base diversity is retained. AMPure XP beads are required.
Yes. Watchmaker's quality management system is certified to ISO 13485:2016.