hapCon: estimating contamination of ancient genomes by copying from reference haplotypes

Area of Science:

• Genetics
• Bioinformatics
• Paleogenomics

Background:

• Ancient DNA (aDNA) studies are crucial for understanding human history.
• Poor DNA preservation leads to contamination, requiring accurate estimation.
• Existing methods struggle with ultra-low coverage aDNA (<0.1×).

Purpose of the Study:

• To develop a robust method for estimating male aDNA contamination at low coverages.
• To improve the reliability of contamination estimates in paleogenomic research.

Main Methods:

• Developed hapCon, a method using a Li&Stephens haplotype copying model for X chromosomes.
• Modeled mismatches as errors or contamination.
• Assessed hapCon on simulated and empirical low-coverage aDNA data.

Main Results:

• hapCon outperforms ANGSD in estimating male X chromosome contamination.
• Achieved reliable estimates at coverages as low as 0.1× (SNP capture) and 0.02× (whole genome).
• Demonstrated low bias for contamination up to 30% across diverse ancestries and ancient samples (~45,000 years).

Conclusions:

• hapCon significantly advances contamination estimation for low-coverage male aDNA.
• The method extends the reliable coverage limit for paleogenomic analyses.
• hapCon is available as an open-source Python package (hapROH).