Resonance Genomics

Structured Genomic Evidence Infrastructure

Structured aggregation of variant-level evidence for laboratory review and quality control.

Resonance Genomics develops structured genomic evidence systems for internal laboratory review and variant reanalysis workflows.

Available for research-use evaluation by qualified laboratories.

Scientific Background

Resonance Genomics workflows are developed by a clinical genomics scientist with over a decade of experience in diagnostic laboratory variant interpretation, genomic assay design, and clinical sequencing workflow development.

Contact for Laboratory Evaluation

WHAT WE BUILD

Modular genomic evidence infrastructure designed for laboratory evaluation workflows.

PCR Primer QC Pre-screening

Independent quality control of PCR primers with emphasis on detecting common population variants within primer binding sites (gnomAD) — a known potential source of allele dropout or amplification bias in sequencing assays [1].

The analysis also evaluates primer locations relative to segmental duplication regions, where highly homologous genomic sequences may increase the risk of non-specific amplification [2]. In such regions, laboratories sometimes consider alternative strategies such as long-range PCR or locus-specific assay design.

Intronic Variant Mapping for Panel Optimization and Variant Discovery

Pathogenic variants located deep within introns can disrupt normal RNA splicing by activating cryptic splice sites or pseudo-exons, representing an increasingly recognized mechanism of genetic disease [3]. By systematically compiling intronic variants reported in ClinVar and mapping their genomic positions relative to MANE transcripts, this analysis highlights loci where noncoding variation has already been observed. These regions can be useful for evaluating capture designs, identifying potential gaps in sequencing panels, and prioritizing intronic loci for further investigation in both clinical and research studies.

Target Capture Design for Panel and Exome-Based Sequencing

Resonance Genomics generates optimized BED files to support hybrid-capture targeted sequencing panel design and exome-slicing workflows. Target regions, derived from curated transcript models (MANE Select and MANE Plus Clinical), are expanded with configurable padding to ensure coverage of splice donor and acceptor sites and to improve capture performance across exon boundaries.

In addition to coding regions, the design framework allows incorporation of clinically relevant intronic loci identified from curated clinical variant databases. These regions are converted into capture intervals and merged with exon-based targets to produce unified BED files that can be used directly for probe design and hybridization-based enrichment. Probe sets are typically tiled across target regions to maximize hybridization efficiency and sequencing coverage of selected loci [4].

Risk Allele Variant Extraction

Clinical laboratories are increasingly expected to consider variants associated with disease susceptibility in addition to traditional Mendelian pathogenic variants [5]. The ClinGen Low-Penetrance/Risk Allele Working Group has highlighted the need for dedicated approaches to capture and evaluate this class of variants. Resonance Genomics provides workflows that extract variants reported in resources such as the GWAS Catalog and ClinVar within genes of interest and compile structured tables linking genomic coordinates, database identifiers, and supporting publications, enabling laboratories to efficiently review and assess variants that may meet risk-allele criteria.

REFERENCES

  1. Blais J, et al. Risk of Misdiagnosis Due to Allele Dropout and False-Positive Genotyping Results. Journal of Molecular Diagnostics. 2015.
  2. Ghani M, Sato C, Rogaeva E. Segmental duplications in genome-wide significant loci and housekeeping genes; warning for GAPDH and ACTB. Neurobiology of Aging. 2013.
  3. Vaz-Drago R, Custódio N, Carmo-Fonseca M. Deep intronic mutations and human disease. Human Genetics. 2017.
  4. Johnson MG, et al. A universal probe set for targeted sequencing of nuclear genes. Systematic Biology. 2019.
  5. Schmidt RJ, et. Recommendations for Risk Allele Evidence Curation, Classification, and Reporting from the ClinGen Low Penetrance/Risk Allele Working Group. 2024

DATA SOURCES & ATTRIBUTION

Resonance Genomics infrastructure operates exclusively on publicly available and licensed data sources, including but not limited to:

All structured outputs maintain clear source attribution and release-version transparency.

GUIDELINE & THRESHOLD REFERENCE

Resonance Genomics does not apply guideline thresholds, assign evidence strengths, or perform interpretation. Laboratories should consult original guideline publications to determine relevant threshold values.

For reference:
https://cspec.genome.network/

SCOPE & OPERATIONAL BOUNDARIES

Resonance Genomics provides evidence aggregation and documentation support only.

All services support internal laboratory research and review workflows.

PLATFORM PRINCIPLES

CONTROLLED INFRASTRUCTURE ACCESS

Services are available to research laboratories and clinical genomics groups upon request and institutional review.

Laboratory Evaluation

Resonance Genomics workflows are available for evaluation by research and clinical genomics laboratories interested in structured variant evidence aggregation and workflow optimization.

If your laboratory is interested in evaluating these tools or discussing potential collaboration, please contact us.

Contact for Laboratory Evaluation