CodeXome Blog
Notes on variant interpretation, primate genomics, and the edges of clinical science.
Why Evolution Is the Missing Dimension in Variant Interpretation
Human-derived data alone leaves most variation unresolved; evolutionary time is the missing axis of biological evidence.
Why Population Databases Can’t Fix the VUS Crisis
As testing scales to exomes and genomes, allele frequency alone cannot resolve the significance of most rare variants.
Why Human-to-Human Comparisons Miss 99.8% of Evolutionary History
Human-only comparisons capture only recent variation and miss the deep evolutionary constraints that actually define gene function.
Why Variant Interpretation Still Takes Months: The Hidden Cost of Manual Filtering
Why manual filtering remains a major bottleneck in variant interpretation, and how evolutionary evidence opens a scalable path forward.
The VUS Bottleneck Explained (And Why It Is Getting Worse Every Year)
Why the VUS problem persists despite more sequencing, and how evolutionary genomics introduces a biologically grounded new source of evidence.
Why Evolution Matters for Variant Interpretation
Population databases describe what exists in human cohorts, but only evolution can tell you what biology tolerated across 80 million years.
Unveiling the Complexity of Genes, Why the Details Matter
Every gene has its own evolutionary tempo and pressure points, and those patterns are essential to understanding which variants drive disease.
A Great Week at ASHG 2025
We had an incredible time at ASHG 2025 and left energized by the level of interest in new approaches to variant interpretation.
