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LiftOn

Definition
AI-generated

LiftOn is a method that combines DNA and protein alignments to transfer or refine gene annotation between assemblies, aiming to correct errors that arise when annotation is lifted by nucleotide alignment alone.

Topics

Why it matters in GWAS

When switching reference genomes or integrating T2T and GRCh38 coordinates, small indels in exons can shift reading frames; protein-aware lifting reduces mismatches between variant calls and exon annotations that affect loss-of-function and missense classification.

Example usage

"We used LiftOn to harmonize gene models after switching the eQTL pipeline to the complete CHM13-based reference."

References

  • Chao KH, et al. (2025). Combining DNA and protein alignments to improve genome annotation with LiftOn. Genome Res.
  • Ji HJ, Pertea M, Salzberg SL. (2026). Annotating genomes at increased scale and resolution. Nat Rev Genet. https://doi.org/10.1038/s41576-026-00937-3

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