WATCHMAKER DNA LIBRARY PREP KITS with TAPS+

The Power of Positive

Direct 5mC sequencing for multimodal insights

TAPS+ chemistry

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

TAPS+ vs EM-Seq vs Bisulfite

CriteriaTAPS+EM-SeqBisulfite
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
Webinar: Discover TAPS+ for Multimodal InsightsWatch Now

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
SPB
Lig
SPB
PCR
SPB
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)

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