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Rare Event Detection Using Error-corrected DNA and RNA Sequencing

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Consensify: A Method for Generating Pseudohaploid Genome Sequences from Palaeogenomic Datasets with Reduced Error

Axel Barlow, Stefanie Hartmann¹, Javier Gonzalez

¹Institute for Biochemistry and Biology, University of Potsdam, Karl-Liebknecht-Str. 24-25, 14476 Potsdam, Germany.

|January 8, 2020

Summary

Consensify improves ancient DNA analysis by creating pseudohaploid sequences that reduce errors from low-quality data. This method enhances phylogenetic and admixture analyses, offering more reliable ancient genome insights.

Keywords:

D statistics ancient DNA bioinformatics error reduction palaeogenomics sequencing error

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Area of Science:

Genomics
Bioinformatics
Computational Biology

Background:

Palaeogenome analysis commonly converts short read data to pseudohaploid sequences.
Current methods like random read sampling do not adequately control for sequencing errors common in ancient DNA.
These errors can distort phylogenetic, population clustering, and admixture analyses.

Purpose of the Study:

Introduce Consensify, a novel method for generating pseudohaploid sequences from palaeogenomic data.
Address limitations of existing methods by controlling for both coverage bias and sequencing error rates.
Improve the accuracy and reliability of downstream population genetic analyses.

Main Methods:

Consensify generates pseudohaploid sequences by correcting for differential sequencing coverage and reducing error rates.
Error correction is data-driven, requiring no external genomic resources or assumptions like contemporaneous sampling.
The method was evaluated against single read sampling techniques for phylogenetic and population clustering analyses, and for D statistics.

Main Results:

Consensify shows reduced susceptibility to artefacts in phylogenetic and population clustering analyses compared to single read sampling.
Consensify demonstrates greater resistance to false positives in D statistics.
The method is less affected by laboratory protocol biases than other commonly used techniques.

Conclusions:

Consensify offers a robust approach to generating pseudohaploid sequences for palaeogenomic studies.
The method effectively reduces errors and biases, leading to more accurate population genetic inferences.
Consensify is applicable to any low to medium coverage short read datasets, not just palaeogenomic data.