ArticleGenome biology2020
Removing reference bias and improving indel calling in ancient DNA data analysis by mapping to a sequence variation graph.
Article in Genome biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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60 citing papers in PubMed, 136 citations in OpenAlex.
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- Multispecies pangenomes reveal a pervasive influence of population size on structural variation.Science (New York, N.Y.) · 2025Article
- Lessons learned: Recommendations for reproducible paleogenomic data analyses.American journal of human genetics · 2025Review
- SAFARI: pangenome alignment of ancient DNA using purine/pyrimidine encodings.NAR genomics and bioinformatics · 2025Article
- Estimating allele frequencies, ancestry proportions and genotype likelihoods in the presence of mapping bias.G3 (Bethesda, Md.) · 2025Article
- A New Perspective on the Arrival of the Eastern Mediterranean Genetic Influx in Central Italy Before the Onset of the Roman Empire.Genome biology and evolution · 2025Article
- The genomic footprints of migration: how ancient DNA reveals our history of mobility.Genome biology · 2025Review
- Pangenome-aware DeepVariant.bioRxiv : the preprint server for biology · 2025Article
- A survey of sequence-to-graph mapping algorithms in the pangenome era.Genome biology · 2025Review
- A Pangenomic Approach to Improve Population Genetics Analysis and Reference Bias in Underrepresented Middle Eastern and Horn of Africa Populations.Biomolecules · 2025Article
- Comparative population pangenomes reveal unexpected complexity and fitness effects of structural variants.bioRxiv : the preprint server for biology · 2025Article
- Pre-processing of paleogenomes: mitigating reference bias and postmortem damage in ancient genome data.Genome biology · 2025Article
- Resolving the source of branch length variation in the Y chromosome phylogeny.Genome biology · 2025Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundDuring the last decade, the analysis of ancient DNA (aDNA) sequence has become a powerful tool for the study of past human populations. However, the degraded nature of aDNA means that aDNA molecules are short and frequently mutated by post-mortem chemical modifications. These features decrease read mapping accuracy and increase reference bias, in which reads containing non-reference alleles are less likely to be mapped than those containing reference alleles. Alternative approaches have been developed to replace the linear reference with a variation graph which includes known alternative variants at each genetic locus. Here, we evaluate the use of variation graph software vg to avoid reference bias for aDNA and compare with existing methods.
resultsWe use vg to align simulated and real aDNA samples to a variation graph containing 1000 Genome Project variants and compare with the same data aligned with bwa to the human linear reference genome. Using vg leads to a balanced allelic representation at polymorphic sites, effectively removing reference bias, and more sensitive variant detection in comparison with bwa, especially for insertions and deletions (indels). Alternative approaches that use relaxed bwa parameter settings or filter bwa alignments can also reduce bias but can have lower sensitivity than vg, particularly for indels.
conclusionsOur findings demonstrate that aligning aDNA sequences to variation graphs effectively mitigates the impact of reference bias when analyzing aDNA, while retaining mapping sensitivity and allowing detection of variation, in particular indel variation, that was previously missed.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.