Ratio of mitochondrial to nuclear DNA affects contamination estimates in ancient DNA analysis

Furtwängler, Anja; Reiter, Ella; Neumann, Gunnar U.; Siebke, Inga; Steuri, Noah; Hafner, Albert; Lösch, Sandra; Anthes, Nils; Schuenemann, Verena J.; Krause, Johannes

doi:10.1038/s41598-018-32083-0

Cited by 50 publications

(48 citation statements)

References 41 publications

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“…This approach reconstructs the endogenous mitochondrial genome sequence, even when the contamination exceeds 50%, distinguishing between the ancient mitochondrial DNA (amtDNA) and the modern DNA contaminant. These show: (a) a different deamination frequency (the aDNA, if compared to modern DNA, results highly deaminated) and (b) a diverse length of the fragments (the aDNA tends to be fragmented in shorter molecules, of ~60 bp, with respect to the modern DNA) . However, this approach is not always appropriate by studying the reliability of the nuclear contamination extrapolation from mitochondrial contamination estimates .…”

Section: Mitochondrial Contaminations Of the Ancient Dnamentioning

confidence: 99%

“…They found that the mitochondrial to nuclear DNA (mtDNA/ncDNA) ratio negatively correlates with the increase of the endogenous DNA content and strongly influences mitochondrial and nuclear contamination estimates. In detail, they showed that the contamination of ncDNA tends to be underestimated in samples of aDNA with a value of the mtDNA/ncDNA ratio > 200, while the results were more reliable for aDNA samples with a mtDNA/ncDNA ratio < 200 …”

Section: Mitochondrial Contaminations Of the Ancient Dnamentioning

confidence: 99%

“…15,62 However, this approach is not always appropriate by studying the reliability of the nuclear contamination extrapolation from mitochondrial contamination estimates. 62 The authors analyzed aDNA from 317 samples of different skeletal elements from multiple sites, spanning a temporal range from 7,000 before present to 386 anno domini, considering the mtDNA/ncDNA ratio. They found that the mitochondrial to nuclear DNA (mtDNA/ncDNA) ratio negatively correlates with the increase of the endogenous DNA content and strongly influences mitochondrial and nuclear contamination estimates.…”

Section: Mitochondrial Contaminations Of the Ancient Dnamentioning

confidence: 99%

“…In detail, they showed that the F I G U R E 1 Schematic representation of general protocols useful to identify bacterial contaminations, contaminations of human origin, and mitochondrial contamination of ancient DNA contamination of ncDNA tends to be underestimated in samples of aDNA with a value of the mtDNA/ncDNA ratio > 200, while the results were more reliable for aDNA samples with a mtDNA/ncDNA ratio < 200. 62 Summarizing, the mtDNA represents a good target locus to study the contaminant DNA in mixed aDNA samples. Schmutzi is an iterative approach that uses the mtDNA to identify the contaminant DNA, using data from present-day individuals, in aDNA sequences deposited in databases.…”

Section: Mitochondrial Contaminations Of the Ancient Dnamentioning

confidence: 99%

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Contaminations in (meta)genome data: An open issue for the scientific community

Pasquadibisceglie

Proietto

et al. 2019

IUBMB Life

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In recent years, the high throughput and the low cost of next‐generation sequencing (NGS) technologies have led to an increase of the amount of (meta)genomic data, revolutionizing genomic research studies. However, the quality of sequencing data could be affected by experimental errors derived from defective methods and protocols. This represents a serious problem for the scientific community with a negative impact on the correctness of studies that involve genomic sequence analysis. As a countermeasure, several alignment and taxonomic classification tools have been developed to uncover and correct errors. In this critical review some of these integrated software tools and pipelines used to detect contaminations in reference genome databases and sequenced samples are reported. In particular, case studies of bacterial contaminations, contaminations of human origin, mitochondrial contaminations of ancient DNA, and cross contaminations are examined.

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Section: Mitochondrial Contaminations Of the Ancient Dnamentioning

confidence: 99%

Section: Mitochondrial Contaminations Of the Ancient Dnamentioning

confidence: 99%

Section: Mitochondrial Contaminations Of the Ancient Dnamentioning

confidence: 99%

Section: Mitochondrial Contaminations Of the Ancient Dnamentioning

confidence: 99%

See 2 more Smart Citations

Contaminations in (meta)genome data: An open issue for the scientific community

Pasquadibisceglie

Proietto

et al. 2019

IUBMB Life

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“…Therefore, mtDNA-based contamination estimates have been used as a proxy for overall contamination (Allentoft et al, 2015). Yet, different mitochondrial-to-nuclear DNA ratios in the endogenous source and the human contaminant(s) may lead to inaccurate conclusions (Furtwängler et al, 2018). While the source of this difference has yet to be identified, accurate methods based on nuclear data are needed to estimate the level of human contamination which may have an impact on downstream analyses (Renaud et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

A likelihood method for estimating present-day human contamination in ancient DNA samples using low-depth haploid chromosome data

Moreno-Mayar

Korneliussen

Albrechtsen

et al. 2019

Preprint

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Motivation:The presence of present-day human contaminating DNA fragments is one of the chal-2 lenges defining ancient DNA (aDNA) research. This is especially relevant to the ancient human DNA 3 field where it is difficult to distinguish endogenous molecules from human contaminants due to their 4 genetic similarity. Recently, with the advent of high-throughput sequencing and new aDNA protocols, 5 hundreds of ancient human genomes have become available. Contamination in those genomes has 6 been measured with computational methods often developed specifically for these empirical studies. 7Consequently, some of these methods have not been implemented and tested while few are aimed at 8 low-depth data, a common feature in aDNA datasets. 9Results: We develop a new X-chromosome-based maximum likelihood method for estimating present-10 day human contamination in low-depth sequencing data. We implement our method for general use, 11 assess its performance under conditions typical of ancient human DNA research, and compare it to 12 previous nuclear data-based methods through extensive simulations. For low-depth data, we show that 13 existing methods can produce unusable estimates or substantially underestimate contamination. In 14 contrast, our method provides accurate estimates for a depth of coverage as low as 0.5× on the X-15 chromosome when contamination is below 25%. Moreover, our method still yields meaningful estimates 16 in very challenging situations, i.e., when the contaminant and the target come from closely related 17 populations or with increased error rates. With a running time below five minutes, our method is 18 applicable to large scale aDNA genomic studies. 22 65 contamination via the incorporation of the intrinsic characteristics of endogenous aDNA fragments 66 into the model (Renaud et al., 2015). 67 68Autosomes-based methods 69Sequencing high depth ancient nuclear genomes remains challenging. Therefore, mtDNA-based con-70 2 tamination estimates have been used as a proxy for overall contamination (Allentoft et al., 2015). Yet, 71 different mitochondrial-to-nuclear DNA ratios in the endogenous source and the human contaminant(s) 72 may lead to inaccurate conclusions (Furtwängler et al., 2018). While the source of this difference has 73 yet to be identified, accurate methods based on nuclear data are needed to estimate the level of human 74 contamination which may have an impact on downstream analyses (Renaud et al., 2016). Indeed, 75 most studies rely on nuclear data to answer key biological questions. A recent method (DICE) aims 76 at estimating present-day human contamination for nuclear data (Racimo et al., 2016). It does so 77 by co-estimating contamination, sequencing error, and demography based on autosomal data. This 78 method generally requires an intermediate depth of coverage (at least 3×) and produces more accurate 79 results when the sample and the contaminant are genetically distant (e.g. different species or highly 80 differentiated populations). 81 82 X-chromosome-based methods and a no...

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Present‐Day DNA Contamination in Ancient DNA Datasets

Peyrégne

Prüfer

2020

BioEssays

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Present‐day contamination can lead to false conclusions in ancient DNA studies. A number of methods are available to estimate contamination, which use a variety of signals and are appropriate for different types of data. Here an overview of currently available methods highlighting their strengths and weaknesses is provided, and a classification based on the signals used to estimate contamination is proposed. This overview aims at enabling researchers to choose the most appropriate methods for their dataset. Based on this classification, potential avenues for the further development of methods are discussed.

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Ratio of mitochondrial to nuclear DNA affects contamination estimates in ancient DNA analysis

Cited by 50 publications

References 41 publications

Contaminations in (meta)genome data: An open issue for the scientific community

Contaminations in (meta)genome data: An open issue for the scientific community

A likelihood method for estimating present-day human contamination in ancient DNA samples using low-depth haploid chromosome data

Present‐Day DNA Contamination in Ancient DNA Datasets

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