TAP-Seq: Bisulfite-Free DNA Methylation, Variant, and Fragmentation Sequencing
Bisulfite-free methylation + variant calling + fragmentomics—built for clean signals and confident interpretation (RUO).
From sample QC and optimized library construction to bioinformatics and reporting, we help you capture DNA methylation while preserving sequence complexity for reliable mapping, variant detection, and fragmentation analysis.
Get a clear plan for inputs, depth, replicates, and expected outputs—so your study is designed right from day one.
Bisulfite-free chemistry to help preserve DNA integrity and library complexity
One library, multi-layer readouts: methylation calls, variants, and fragmentation metrics (RUO)
Interpretation-ready deliverables: tables, tracks, and publication-style plots you can use immediately
TAP-Seq (TET-Assisted Pyridine borane Sequencing Plus) is a next-generation sequencing methodology that enables the concurrent acquisition of high-resolution data on genetic variation, DNA methylation, and DNA fragmentation patterns from a single library. This integrated approach eliminates the need for separate library preparations and experiments, thereby reducing costs and experimental complexity. It delivers perfectly synchronized multi-omics data from a unified workflow, providing cohesive insights for mechanistic studies.
What is TAP-Seq
TAP-Seq is a bisulfite-free sequencing method that directly detects DNA methylation at single-base resolution while preserving the original genetic sequence. Unlike traditional bisulfite sequencing (WGBS), which destructively converts unmethylated cytosines (C) to uracil (U), TAP-Seq uses a "forward conversion" approach.
It employs a TET enzyme to oxidize methylated cytosines (5mC and 5hmC) to 5-carboxylcytosine (5caC), which is then specifically converted to dihydrouracil (DHU) using pyridine borane. During PCR, DNA polymerase reads DHU as thymine (T). This allows methylated sites to be read directly as C-to-T transitions in the sequencing data, while the rest of the genome remains intact for accurate variant calling.
The schematic diagram of the technical principle is as follows:
Why Choose TAP-Seq
Reduce Sample Use & Cost：TAP-Seq uses one library to capture whole-genome methylation and genetic variants simultaneously, cutting sample use—ideal for rare samples—and eliminating extra costs from separate preparations.
Integrated Multi-Omics in One Run：A single TAP-Seq run detects SNVs, Indels, CNVs, methylation, and fragmentomics. This unified approach removes batch effects, ensures data consistency, and enables layered biological insights.
Broad Sample Compatibility：TAP-Seq is compatible with challenging samples like FFPE tissues and cfDNA. Its gentle chemistry preserves DNA integrity, supporting degraded or low-input samples and retrospective studies.
Flexible Platform Support：The method works on both short- and long-read sequencers, leveraging the cost-efficiency of short reads and the structural-resolution power of long reads.
Streamlined Data Analysis：TAP-Seq data fits standard genomic pipelines. Compatible with standard aligners and integrates methylation calling with conventional variant pipilines.
TAP-Seq enables groundbreaking research across diverse fields by providing an integrated molecular view.
Complex Disease & Cancer Research:
Mechanism Discovery: Simultaneously identify driver mutations and epigenetic silencing events (e.g., promoter hypermethylation) to build complete oncogenic models.
Biomarker Discovery: Develop robust diagnostic and prognostic signatures by combining mutation profiles, methylation changes, and fragmentomics features from liquid biopsies.
Methylation Dynamics：Monitoring the temporal dynamics of methylation patterns (e.g., following exposure to demethylating agents) and their concomitant evolution with genetic variants linked to resistant phenotypes.
Population & Quantitative Epigenetics:
mQTL Mapping: Perfectly harmonized genotype and methylotype data from the same library provides the gold standard for discovering genetic variants that regulate DNA methylation levels across populations and tissues.
Developmental & Stem Cell Biology:
Study coordinated genetic and epigenetic reprogramming during differentiation and development from a single assay.
Agricultural & Animal Science:
Apply cost-effective multi-omics to non-human samples, including challenging FFPE specimens from veterinary pathology, to study traits, diseases, and development.
Service workflow
TAP-Seq Service: Step-by-Step Process
Bioinformatics
Bioinformatics Analysis
CD Genomics deliver a complete analysis package. Our standard pipeline includes:
Primary Data Processing：High-quality reads, alignment to reference genome (using standard aligners), and deduplication
DNA Methylation Calling：Base-resolution methylation ratios (beta-values) for all CpG sites. Identification of Differentially Methylated Regions (DMRs).
Genetic Variant Calling：High-confidence calls for Single Nucleotide Variants (SNVs), Insertions/Deletions (Indels), and Copy Number Variations (CNVs).
Fragmentomics Analysis：Genome-wide fragmentation profile analysis, including size distribution and nucleosome positioning patterns.
Integrated Multi-Omics Report: A consolidated report linking findings across genetic, epigenetic, and fragmentomics layers, with functional annotation.
Custom analyses, such as mQTL mapping, sophisticated biomarker model building, or integration with your existing RNA-seq data, are available upon request.
Sample Requirements
Sample Requirements
We optimize protocols for a wide range of sample types:
Sample Type
Minimum Amount
Key Quality Notes
Genomic DNA
≥ 100 ng
High purity (A260/280 ≈ 1.8) in TE or water
Fresh/Frozen Tissue
≥ 10 mg
Snap-frozen, avoid RNAlater
Cultured Cells
≥ 2 x 106cells
Pelleted washed with PBS
Whole Blood
≥ 0.5 mL
EDTA or citrate tubes preferred
FFPE Sections
≥ 15 slides (4-10 µm)
Tumor cell purity >30% recommended
Plasma/Serum cfDNA
≥ 15 ng cfDNA
Isolated using recommended kits
Note:We accept samples from human, mouse, rat, and other common model organisms. Please contact us for specific requirements for other species or unique sample types.
Advantage
Why Choose CD Genomics for TAP-Seq?
Proven Expertise in Advanced Sequencing: We are an early adopter and service provider for cutting-edge methods like TAP-Seq. Our team has deep experience in both library preparation and the complex bioinformatics required for multi-omics data.
End-to-End Project Support: From initial design to final data interpretation, you work with a dedicated project manager and analyst who understand the biological context of your research.
Commitment to Data Quality & Transparency: We provide detailed QC metrics at every step—from sample qualification and conversion efficiency to final data output—so you can trust your results.
Scalable and Cost-Effective Solutions: We offer flexible pricing models for projects of all scales, from pilot studies to large-scale population cohorts, maximizing the impact of your research budget.
