Ref H2
Computational Service
Confidence Reported
Scoped After Feasibility Review
Service Overview
Variant analysis turns sequencing reads into an interpretable list of genomic changes and, more importantly, into a judgement about which of them matter. We call SNVs, indels, copy number changes and structural variants using established best-practice workflows, annotate them functionally and clinically, and classify them by predicted consequence. Both germline and somatic settings are supported, including tumour–normal paired analysis, tumour mutational burden and mutational signature extraction.
Key Features & Advantages
Best-Practice Calling Workflows
Alignment, duplicate marking, recalibration and filtering follow established consortium recommendations, with parameters recorded so the calls can be defended and repeated.
All Variant Classes
SNVs, indels, copy number and structural variants are called together, because restricting analysis to point mutations misses a substantial share of driver events.
Interpretation, Not Only Annotation
Variants are prioritised by predicted functional impact, population frequency, clinical evidence and relevance to your biological question, rather than handed over as a raw annotated file.
Coverage Honestly Reported
Regions with insufficient depth are identified explicitly, so absence of a variant call in a poorly covered region is not mistaken for absence of a variant.
Where This Service Is Used
1Identifying candidate causal variants in rare disease or family studies
2Somatic mutation profiling of tumour samples with matched or unmatched normals
3Calculating tumour mutational burden and extracting mutational signatures
4Characterising resistance mutations arising in treated patients or cell models
5Verifying the genomic integrity of engineered cell lines or models
Methods and Techniques Applied
1Read quality control, alignment, duplicate marking and base quality score recalibration
2Germline calling with joint genotyping, and somatic calling with paired or panel-of-normals approaches
3Copy number and structural variant detection with purity and ploidy estimation for tumour samples
4Functional annotation covering consequence, population frequency, conservation and predicted pathogenicity
5Clinical and knowledge base annotation against curated variant resources
6Prioritisation and, where requested, mutational signature and tumour mutational burden analysis
What We Need From You
1FASTQ, BAM or VCF files with the capture kit or library preparation described
2Sample metadata including tumour–normal pairing, tissue type and any known variants
3The question: diagnostic candidate search, driver discovery, resistance profiling or quality verification
4Species and reference build preference, with any custom regions of interest
What You Receive
1Annotated variant files in VCF and tabular form, with all annotation fields documented
2Prioritised candidate list with the evidence supporting each variant
3Coverage and quality report including regions with insufficient depth
4Copy number and structural variant summaries with visualisation
5Signature, burden and comparative analyses where they were part of the scope
What We Compute and Report
1Variant calls with quality scores, allele fractions and genotype confidence
2Functional consequence, population frequency and pathogenicity predictions per variant
3Copy number profiles with tumour purity and ploidy estimates where applicable
4Coverage statistics with the regions too shallow to support a negative result identified
5Mutational signature contributions and tumour mutational burden where in scope
Questions We Are Asked Before Scoping
Can you provide clinical interpretation?
▸We provide research-use annotation and prioritisation, including evidence from clinical knowledge bases. Clinical diagnostic reporting requires an accredited laboratory and is outside our scope.
What if we have no matched normal?
▸Tumour-only calling is possible using panels of normals and population filtering, but germline contamination of the somatic call set is unavoidable. We quantify the limitation rather than ignore it.
Is exome or genome sequencing better?
▸Exome sequencing is cheaper per sample and sufficient for coding variants. Whole genome sequencing is needed for regulatory regions, structural variants and accurate copy number. We advise based on your question before sequencing where possible.
Interpretation and Limitations
Computational predictions prioritise hypotheses; they do not independently establish binding, biological activity, therapeutic efficacy, safety or clinical validity. Performance depends on input quality, target class, the structural evidence available and the applicability domain of the selected methods. Scores used for ranking are comparative devices and should not be read as measured quantities. All deliverables are for research use only and are not intended for diagnostic or therapeutic use.
Is This the Right Service for You?
Choose this when
Candidate causal variants must be identified in a rare disease or family study
Somatic profiling is needed with or without matched normals
Mutational burden or signatures are required for a translational question
Consider another service when
Expression rather than genotype is the question
Bulk & Single-Cell RNA-Seq Analysis A predictive model on clinical variables is the goal
Clinical Prediction Modeling What Goes Wrong, and How We Handle It
These are the failure modes that produce confident-looking results which do not survive the next experiment. Each one is designed against rather than discovered afterwards.
Absence of a variant call read as absence of a variant
Coverage is reported per region, and areas too shallow to support a negative conclusion are identified explicitly.
Germline variants contaminating a tumour-only somatic call set
Panels of normals and population filtering are applied, and the residual limitation is quantified rather than ignored.
Pathogenicity predictions treated as clinical interpretation
Annotation is research-use; clinical reporting requires an accredited laboratory and is outside our scope.
A Worked Example
Reprocessing an exome trio that had produced no candidate
The situation
A previous analysis reported no plausible causal variant, and the referring clinicians suspected the pipeline.
What the work involved
The data was reprocessed from raw reads with recalibration and joint genotyping, coverage was assessed across the candidate gene panel, and structural and copy number calling was added.
What came back
Three exons of the strongest candidate gene had fallen below callable coverage. Targeted re-analysis revealed a small deletion that the original variant-only pipeline could not have detected.
Illustrative of the shape this work takes. Details are generalised, no client or target is identified, and scope and outcome vary with the system in question.
Service Workflow
1
Scientific Consultation
We discuss the objective, the decision it supports and the data you hold. Nothing is quoted before we understand what the result has to answer.
2
Feasibility Review
We check that the data, target class and available structural evidence can support the proposed approach, and say plainly where they cannot.
3
Technical Proposal
Scope, methods, deliverables, timeline and price are confirmed in writing, together with the limitations we expect to report.
4
Computation and QC
The analysis runs on pinned tool versions in a containerised environment, with quality checkpoints and method comparison where that is informative.
5
Report and Follow-Up
You receive the ranked results, the documented methods, the limitations and a proposed validation plan, plus support in interpreting them.
Service Process
1
Online Consultation
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2
Solution Matching
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3
Service Contract
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4
Project Execution
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5
Data Delivery
Specifications & Turnaround
Note: ICDMO delivers computational (in silico) services. Results prioritise hypotheses for testing; they do not by themselves establish binding, biological activity, efficacy or safety. All deliverables are for research use only and are not intended for diagnostic or therapeutic use. Downstream experimental work is scoped separately and executed through qualified partners.
Get a Custom Quote
Our scientific team responds within 24 hours with a detailed technical proposal and pricing tailored to your project.
Contact Us Online ConsultationStandard Deliverables
✓Sequence-verified final product
✓Full QC documentation
✓Certificate of Analysis (CoA)
✓Electronic data files
✓Project completion report
Why ICDMO?
Computational CDMO Focus
Reproducible, Versioned Pipelines
Confidence & Limitations Reported
Experiment-Aware Recommendations
Response Within One Business Day