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Recovering High-Quality Host Genomes from Gut Metagenomic Data through Genotype Imputation.

Sofia Marcos1, Melanie Parejo1, Andone Estonba1

  • 1Applied Genomics and Bioinformatics University of the Basque Country (UPV/EHU) Leioa Bilbao 48940 Spain.

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PubMed
Summary

Discarded host DNA from metagenomic data can now be used for genetic analysis. A new imputation strategy successfully reconstructs host genotypes from low-depth sequencing data, enabling population genetics insights.

Keywords:
hostimputationmetagenomic datapopulation genetics

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Area of Science:

  • Genomics
  • Population Genetics
  • Microbiome Research

Background:

  • Metagenomic studies often discard host DNA due to low data yield.
  • Host genetic information is valuable for understanding host-microbe interactions and population structure.
  • Genotype imputation offers a potential solution for reconstructing host genotypes from limited data.

Purpose of the Study:

  • To evaluate a genotype imputation strategy for low-depth host DNA from metagenomic samples.
  • To assess the performance of different reference panels for host genotype imputation.
  • To determine the impact of imputation on population genetics analyses.

Main Methods:

  • A two-step genotype imputation strategy was applied to low-depth host genome data (≈2× coverage).
  • Four distinct reference panels were constructed and tested.
  • Imputation accuracy was assessed using samples with both low- and high-depth sequencing data.
  • Population genetics statistics were calculated for 100 chickens using imputed genotypes.

Main Results:

  • High imputation accuracies (>0.90) were achieved across all tested reference panels.
  • The choice of reference panel had minimal impact on population genetics statistics.
  • The imputation strategy successfully leveraged discarded host DNA for genetic insights.

Conclusions:

  • The developed imputation strategy is feasible for reconstructing host genotypes from low-depth metagenomic data.
  • This method allows for the utilization of previously discarded host DNA for population genetics studies.
  • The approach facilitates the implementation of hologenomic studies, integrating host and microbial genomic data.