Pre-processing of paleogenomes: mitigating reference bias and postmortem damage in ancient genome data

Koptekin D., Yapar E., Vural K. B., Sağlıcan E., ALTINIŞIK N. E., Malaspinas A., ...More

Genome biology, vol.26, no.1, pp.6, 2025 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 26 Issue: 1
  • Publication Date: 2025
  • Doi Number: 10.1186/s13059-024-03462-w
  • Journal Name: Genome biology
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, CAB Abstracts, EMBASE, MEDLINE, Veterinary Science Database, Directory of Open Access Journals
  • Page Numbers: pp.6
  • Keywords: Ancient DNA, Graph-reference genome, Masking, Post-mortem damage, Reference bias
  • Middle East Technical University Affiliated: Yes

Abstract

We investigate alternative strategies against reference bias and postmortem damage in low coverage paleogenomes. Compared to alignment to the linear reference genome, we show that masking known polymorphic sites and graph alignment effectively remove reference bias, but only starting from raw read files. We next study approaches to overcome postmortem damage: trimming, rescaling, and our newly developed algorithm, bamRefine (github.com/etkayapar/bamRefine and zenodo.org/records/14234666), masking reads only at positions possibly affected by PMD. We propose graph alignment coupled with bamRefine as a simple strategy to minimize data loss and bias, and urge the community to publish FASTQ files.