--- title: ctDNA Methodology | Tumour-naive, SNV and SV description: Compare tumour-naive, SNV-based and SV-based ctDNA strategies and see which fits your samples, sensitivity needs and timelines. 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Design a trial assay →](https://simsendiagnostics.com/solutions-trials?hsLang=en) [For research and labs Translational oncology See signal in paediatric and early-stage samples your current platform misses. Send samples or run SiMSen-Seq in-house. See the signal →](https://simsendiagnostics.com/solutions-research?hsLang=en) [For clinics Premium oncology monitoring Detect minimal residual disease ahead of imaging. Logistics across the EU, UK and EEA. Detect relapse earlier →](https://simsendiagnostics.com/solutions-clinic?hsLang=en) [Home](https://simsendiagnostics.com?hsLang=en) / [Platform](https://simsendiagnostics.com/platform?hsLang=en) / Methodology Methodology compared # Three ways to monitor ctDNA. *They are not interchangeable*. Tumour-informed monitoring splits broadly into three approaches: tracking single nucleotide variants, tracking structural variants, or using fixed tumour-naive panels. Each has consequences for your samples. Most platforms hide this choice. We think it deserves daylight. At a glance ## The three approaches, in plain terms. Each is a real, valid methodology. Each is the right answer for a different set of samples and a different clinical question. Simsen approach ### SNV-based Personalised and ultra-sensitive, surfacing clinically actionable variants alongside tumour markers. **Best when:** small biopsies, low tumour burden, you want resistance signal. ### SV-based Personalised, sensitive in tumour types with high structural-variant burden, but no resistance information. **Best when:** SV-rich tumours, resistance tracking not required. ### Tumour-naive Fixed panel, no biopsy needed, lower sensitivity at very low allele frequencies. **Best when:** no tissue available, sensitivity is secondary. Side by side ## What each approach actually delivers, attribute by attribute. | Attribute | SNV-basedSimsen Approach | SV-based | Tumour-naive | | --- | --- | --- | --- | | Limit of detection (VAF) | ✓~0.001% (panel-level) per-variant ~0.01%; aggregate across the ~20–30 variant panel ~0.001% with consensus depth. | ✓~0.01% SV-breakpoints provide strong signal, where present. | ~0.1-1% Limited by fixed panel background error | | Tumour tissue required | ✓Yes FFPE block or fresh sample, once, for panel design. | ✓Yes For SV characterisation. | –No Fixed panel, no biopsy needed. | | Actionable resistance variants | ✓Yes Personalised panel surfaces clinically actionable and resistance variants. | –No SV breakpoints carry no resistance information. | –Limited Only variants on the fixed panel are returned. | | Performance in small biopsies / low input | ✓Strong 10-50 ng cfDNA input. Validated on paediatric and surgical samples. | ~Variable Depends on SV burden in the tumour type | ~Weaker Lower sensitivity makes low-input cases marginal. | | Longitudinal monitoring | ✓Yes Same personalised panel reused across plasma points. | ✓Yes Same SV panel reused. | ✓Yes Fixed panel reuse | | Panel design lead time | ~2-3 weeks From tumour sample receipt. One-off; subsequent plasma runs are standard turnaround. | ~2-3 weeks SV characterisation adds time. | ✓None Off-the-shelf, no design time | | Cost per sample | ~Low-high Personalised design cost amortised across longitudinal samples. Many timepoints decrease cost per sample to lesser than tumour-naive panels. | ~Mid-high Similar economics to SNV-based. | ✓Lower Off-the-shelf, lower per-sample cost. | | Raw data access | ✓Yes FASTQ + BAM. Open pipeline. Bring your own bioinformatics in. | ~Vendor-dependent Varies by provider. | ~Vendor-dependent Often summary only. | Choosing well ## When each approach is the right choice, including when ours is not. We are tumour-informed SNV specialists, and we will say so when another method is a better fit for your samples. The clinical question, the sample type and the tissue availability decide the methodology, in that order. Choose SNV-based when ### Sensitivity is the constraint and tissue is available. - Minimal residual disease monitoring after curative-intent treatment. - Paediatric tumours, low-burden cases, small biopsies. - You need actionable variants and resistance tracking, not just yes/no. - Co-publication, raw data and pipeline transparency matter to you. Choose SV-based when ### The tumour type carries strong SV signal and resistance is not the question. - SV-rich tumour types where breakpoints are well characterised. - You want personalised tracking but resistance variants are not the clinical question. - SV-specific bioinformatics expertise is available in your team or your provider. Choose tumour-naive when ### No tissue, broad surveillance, or sensitivity is secondary. - No tumour tissue available for personalised panel design. - Population-level screening or broad surveillance use cases. - Sensitivity at low VAF is not the deciding factor for your question. - You need a faster, lower-cost per-sample option and can accept the trade-off. Decision guide ### Four questions to your best-fit methodology. Answer four short questions about your samples, your tumour type and your clinical question. The guide returns the methodology that fits, with a transparent reason for the recommendation, even when it is not ours. 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