CRISPR screens: from a selected hit to a defensible mechanism
A screen identifies candidates under particular experimental conditions; orthogonal evidence is needed before treating a hit as a disease mechanism or therapeutic target.
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20 articles
Functional variant assays: abnormal biology is not automatically pathogenicity
Assay validation, disease mechanism and clinical calibration determine whether a laboratory observation can strengthen variant classification.
DNA methylation episignatures: biomarkers with a defined scope
A reproducible methylation pattern can support a diagnosis, but classifier coverage and validation determine how much it can resolve.
Single-cell genomics: more cells do not replace more participants
Cell atlases reveal biological heterogeneity, but meaningful disease comparisons require sound sampling, batch handling and independent replication.
Long-read sequencing: match the technology to the unresolved mechanism
Longer molecules can clarify structural variation and difficult regions, but analytical validation and study design still determine diagnostic value.
Clinical RNA sequencing: connecting a DNA change to its consequences
Transcriptome analysis can reveal abnormal splicing or expression, but tissue choice and assay context determine what a negative result means.
Trio sequencing: what parental samples add to interpretation
Family sequencing can clarify inheritance and reduce the candidate list, while leaving important limits around mosaicism and clinical causality.
Tumour and germline testing: two questions that can intersect
A cancer sequencing result may guide treatment, raise an inherited-risk question, or both—but it cannot be interpreted without knowing the sample and test.
Polygenic scores in clinic: prediction requires calibration and context
A high percentile is not an absolute risk, and strong association does not establish that using a score improves care.
Penetrance and expressivity: why a genetic finding cannot tell the whole future
The same genetic condition can affect people differently. Penetrance and expressivity help explain what a genetic result can—and cannot—predict.
Rare-disease trial endpoints: measure a change that matters
Small populations make endpoint selection more demanding, not less; connect measurement quality, natural history and patient relevance.
Gene therapy evidence: distinguish early response from durable benefit
A one-time administration still requires long-term evidence about effectiveness, late adverse events and who remains represented in follow-up.