Two Omics, One Library:
TAPS+ on DNBSEQ Unlocks Methylation and Variant Data in a Single Run
Key Takeaways
Summary
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Dual-Omics in One Run: The TAPS+ workflow on MGI DNBSEQ platforms enables simultaneous methylation profiling and SNP variant calling from a single library.
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Ultra-Low Sample Input: Generates high-quality data from as little as 1 ng of DNA, making it ideal for low-yield or degraded FFPE and cfDNA samples.
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High Data Efficiency & Accuracy: Preserves near-native sequence diversity with ~40% GC content, eliminating the need for balancing control spike-ins and achieving >0.965 correlation with 935K methylation arrays.
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Scalable Throughput: Fully supported across MGI DNBSEQ-T1+ and DNBSEQ-T7+ platforms to accommodate pilot studies up to large-scale global cohorts.
Overcoming Bisulfite Bottlenecks: Enzymatic TAPS+ on MGI DNBSEQ
DNA methylation is a core epigenetic modification that plays a pivotal role in gene expression regulation, tumorigenesis, and embryonic development, making it a critical research direction for disease biomarker screening, cohort studies, and liquid biopsy. However, conventional bisulfite sequencing, the classic method for methylation detection, has inherent limitations:
- High sample input demand: The harsh chemical reaction causes severe DNA degradation, imposing strict requirements on starting sample quantity.
- Reduced sequence complexity: Full conversion of unmethylated cytosines produces a highly skewed base composition and markedly reduced nucleotide diversity genome-wide. This low-diversity library profile requires balanced control spike-ins to support stable base calling, and elevates the difficulty of sequencing and read alignment.
- Incompatible with co-detection of variants: Converted sequences lose native genomic base information, so genomic variant analysis requires separate library preparation, further consuming precious samples.
For clinical cohort research, low-yield, degraded FFPE and cfDNA samples frequently face library construction failure and fluctuating data quality. Parallel methylation and mutation analyses also raise costs and introduce batch effects — a widespread bottleneck for research progress. TAPS+ changes that. The enzyme-based TAPS+ technology selectively converts only methylated cytosines, preserves near-native genomic sequences, enables simultaneous methylation and variant detection in one run, and causes minimal DNA damage, making it highly compatible with low-input degraded samples.
Recently, MGI demonstrated compatibility of the TAPS+ workflow on DNBSEQ platforms. Backed by DNBSEQ’s high accuracy, low duplication, and low GC bias, the solution reliably generates high-quality data from as little as 1 ng input — delivering two omics (methylation + variants) from a single library, while reducing sample consumption, costs, and turnaround time.
Method
To systematically evaluate the performance and compatibility of the TAPS+ workflow on DNBSEQ platforms, we tested multiple sample types across a range of input amounts:
- Reference standard: NA12878 human genomic DNA, tested at 180 ng, 100 ng, 50 ng, and 1 ng input levels
- Challenging samples: FFPE tissue (50 ng, 1 ng) and plasma cfDNA (20 ng, 5 ng)
- Conversion controls: Methylated Lambda DNA and unmethylated pUC19 DNA for efficiency and specificity validation
All libraries were prepared using the TAPS+ methylation library prep kit and MGI adapters, processed into DNA nanoballs (DNBs) via a one-step DNB preparation protocol, then sequenced on the DNBSEQ-T1+ and T7+ platforms. Downstream analyses included sequencing quality control, methylation calling and conversion efficiency assessment, SNP variant detection performance evaluation, and concordance comparison against the 935K methylation microarray benchmark.
Sequencing Data QC — Reliable Data Quality Across All Input Levels
This robust, consistent performance is underpinned by the inherent strengths of MGI's DNBSEQ technology: high base accuracy, low duplication rates, and minimal sequencing bias. It ensures high data validity even from challenging samples, and delivers measurable cost efficiency for large-scale global cohort studies.
Reliable Performance with FFPE and cfDNA Samples
Figure 2 summarises the core quality control metrics — including mapping rate and ≥20× coverage — across NA12878, FFPE, and cfDNA samples.
All groups maintain uniformly high mapping rates. Even at the lowest tested input levels, both key metrics remain comparable to the NA12878 reference standard, with no marked performance attenuation. These results demonstrate strong adaptability of the TAPS+ DNBSEQ workflow to high-difficulty clinical samples, supporting reliable research use of precious, low-yield specimens.
Accurate Methylation Signals with Biological Relevance
High conversion specificity is the foundation of trustworthy methylation data. Measured by naturally rare CHG/CHH methylation levels:
Additional conversion efficiency validation:
These results confirm the assay accurately detects truly methylated sites while minimising false-positive calls.
Single Library, Dual Discovery: Simultaneous Methylation and Variant Calling
Unlike traditional BS-seq, TAPS+ encodes methylation information via base conversion while preserving native genomic sequence data. This allows researchers to get both methylation profiles and variant calls from one library preparation and one sequencing run.
High Concordance with 935K Methylation Array
The data shows high concordance with the established 935K methylation microarray benchmark, confirming robust, high-fidelity methylation calling across the ecosystem:
This high concordance remains stable across all four input levels (180 ng to 1 ng), confirming reliable, publication-quality methylation quantification.
Dual Platform Flexibility for Projects of All Scales
MGI’s DNBSEQ-T7+ and DNBSEQ-T1+ cover the full lifecycle of cohort research, with fully compatible data output for seamless scaling.
Both platforms deliver ~98% Raw Q30 and support direct double-stranded DNA input. Critically, TAPS+ libraries deliver data throughput equivalent to standard whole-genome sequencing (WGS) on both platforms — the methylation workflow does not compromise read output or sequencing capacity.
Solution Highlights
Powered by MGI DNBSEQ platforms, TAPS+ technology redefines what is possible in epigenetic research:
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Reliable detection from limited specimens: Delivers consistent performance with 50 ng input, and remains viable even at 5 ng or 1 ng ultra-low input.
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Efficient utilisation of precious samples: Generates biologically meaningful data from archived FFPE and cfDNA specimens.
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Dual-omics output: Simultaneous methylation and variant detection halves sample usage, sequencing cost, and turnaround time.
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Research-grade data reliability: >0.965 concordance with the 935K array, with genome-wide methylation coverage.
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Scalable platform options: T1+ for pilot studies and small cohorts, T7+ for high-throughput projects, with end-to-end workflow support.
For Research Use Only. Not for use in diagnostic procedures. TAPS+ products are provided by Watchmaker Genomics.
