WATCHMAKER DNA LIBRARY PREP KITS with TAPS+

The Power of Positive

Direct 5mC sequencing for multimodal insights

The Power of Positive

Direct 5mC sequencing
for multimodal insights

Traditional methyl-seq workflows convert unmethylated Cs to Ts, which effectively collapses sequence complexity from four bases (ATCG) to three (ATG), limiting utility to methylation analysis. Bisulfite treatment is also highly damaging to DNA, leading to sequence coverage gaps and sample type and mass compatibility limitations.

TAPS+ is a positive-readout chemistry that directly converts methylated Cs (5mCs) to Ts, and preserves unmethylated Cs. This maintains base complexity (ATCG) and delivers 5mC, SNV/indel, and CNV detection from a single library for multimodal analysis across discovery, translational, and population studies, as well as multi-cancer early detection and monitoring applications.

Comparison of Traditional methyl-seq vs TAPS+ sequencing showing base complexity

Key Features and Benefits

Direct 5mC readout enables simultaneous detection of genetic variants (SNV/Indels and CNVs) and epigenetic modifications from the same library
Greater than 98% 5mC conversion — including both hypo- and hyper-methylated regions — delivers high true positive and low false positive rates
Higher sequence diversity boosts mappability, reduces multi-mapping/low-complexity dropouts, and lifts CpG coverage at a given read depth
Nondamaging workflow delivers robust performance with degraded FFPE and low-input samples (down to 1 ng), including cfDNA
Streamlined, automation-friendly workflow generates libraries in 6 hours — no columns required
Reduce computational analysis time by 30% or more, saving hours and associated costs on a 30X genome

Table 1. Comparison of methyl-seq methods

	TAPS+	EM-Seq	Bisulfite
Methylation detection accuracy	●●●	●●●	●●●
Low false positives	●●●	●●	●●
Base diversity	●●●	●	●
Genomic variant detection	●●●	●●	●
Non-damaging to DNA with high molecular recovery	●●●	●●●	●
Workflow simplicity and automatability	●●●	●●	●●
Reduced computational time and costs	●●●	●	●

Applications

Methyl sequencing as an alternative to bisulfite conversion, including EPIC arrays
Whole-genome or targeted methylation sequencing
Simultaneous detection of methylation, SNV/Indels, and CNVs
Differential methylation analysis
Allele-specific methylation analysis

Multi-cancer early detection (MCED) assay development
Minimal residual disease (MRD) assay development
Tumor profiling, including FFPE
Liquid biopsy (cfDNA/ctDNA) studies
Fragmentomics
Aging studies

Population studies, including epigenome-wide association studies (EWAS)
Cancer research
Neurodegenerative research
Neuroscience and developmental biology
Biomarker discovery
Epigenotyping

Preserved base diversity for robust downstream analyses

Base diversity comparison: hg38 Reference Genome, TAPS+ Genome, and Traditional Methyl-Seq Genome

Figure 1. Sequence a five-base genome. Only ~1–2% of bases in the human genome are cytosines in CpG context, which is where most methylation occurs. TAPS+ converts just those methylated CpG cytosines, leaving the remaining ~20% of cytosines unchanged. The result is a library that preserves native four-base complexity, more closely matches the human genome, and also delivers 5mC detection (the fifth base). This improves alignment and QC metrics, reduces the need for phiX spike-ins, and omits the need for costly methylated adapters. It also enables SNV/indel and CNV calling alongside methylation profiling from a single library.

Highly automatable, single-day workflow

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Watchmaker DNA Library Prep Kit
with TAPS+

ER/AT

Lig

SPB

Oxidation

SPB

Reduction

SPB

PCR

SPB

Bisulfite Conversion +
ssENA Library Prep
(BS-Seq)

Conversion

DecuP

SPB

Adapters

SPB

Lig

SPB

PCR

SFB

NEBNext® Enzymatic
Methyl-seq v2 Kit
(EM-Seq v2)

ER/AT

Lig

Oxidation

Deam

Deamination & extension →

PCR

Time (hrs)

Figure 2. Reduce turnaround time with an automatable workflow. The Watchmaker DNA Library Prep Kit with TAPS+ delivers libraries in under 6 hours with a workflow that smoothly translates to automated liquid handlers for high-throughput processing. The method does not require specialty consumables (like conversion columns often used in bisulfite workflows).

*Bisulfite Conversion = EZ DNA Methylation-Gold Kit (Zymo Research) and ssENA Library Prep = xGen Methyl-Seq Library Prep Kits (IDT)

View the Data

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