Schmutzi: estimation of contamination and endogenous mitochondrial consensus calling for ancient DNA

Abstract

Ancient DNA is typically highly degraded with appreciable cytosine deamination, and contamination with present-day DNA often complicates the identification of endogenous molecules. Together, these factors impede accurate assembly of the endogenous ancient mitochondrial genome. We present schmutzi, an iterative approach to jointly estimate present-day human contamination in ancient human DNA datasets and reconstruct the endogenous mitochondrial genome. By using sequence deamination patterns and fragment length distributions, schmutzi accurately reconstructs the endogenous mitochondrial genome sequence even when contamination exceeds 50 %. Given sufficient coverage, schmutzi also produces reliable estimates of contamination across a range of contamination rates. Availability: https://bioinf.eva.mpg.de/schmutzi/ license:GPLv3.Electronic supplementary materialThe online version of this article (doi:10.1186/s13059-015-0776-0) contains supplementary material, which is available to authorized users.

Ancient individuals from the North American Northwest Coast reveal 10,000 years of regional genetic continuity

“…The D statistic did not reveal a signal of gene flow between Arctic populations (Inuit and Yup'ik) and either the modern or ancient Northwest Coast populations compared with Shuká Káa (Table S2, tests [19][20][21][22][23][24][25][26][27][28]. However, comparing the more recent ancient individuals, the tree was rejected with 939, 302, and 443, indicating greater affinity toward the Northwest Coast populations than the Arctic (Fig.…”

“…Contamination Estimates. Contamination estimates using the mitochondrial genome were run on all three samples using the Scmutzi program described by Renaud et al (26). The method jointly estimates present day human contamination and reconstructs the endogenous mitochondrial genome by considering both deamination patterns and fragment length distributions.…”

Fast, Accurate and Automatic Ancient Nucleosome and Methylation Maps with epiPALEOMIX

“…That the expected out-of-phase signal between nucleosome occupancy patterns and methylation levels was detectable for Bichon, albeit this sample only showed 0.24 mis-incorporations per overhang, is not incompatible with the recommended threshold as the sequencing data were trimmed for the two starting and ending read positions, where cytosine deamination rates are maximal (Jones et al 2015). We should, however, caution that CTCF epigenetic patterns should not substitute the other authentication proxies currently used, for example, based on other features of nucleotide mis-incorporation and DNA fragmentation (Briggs et al 2007; Krause et al 2010) and/or direct estimates of contamination levels (Green et al 2010; Rasmussen et al 2010; Fu et al 2013; Renaud et al 2015: 20; Racimo et al 2016). In contrast to the latter, but similar to the former, CTCF methylation and nucleosome occupancy patterns can indeed be expected in the case of a mixture of modern DNA contaminants and aDNA templates, as long as a sufficient number of deamination-driven nucleotide mis-incorporations are found at overhangs.…”

Human evolution: a tale from ancient genomes

“…The proportion of alternative alleles found can thus be converted in a measure of contamination levels. For mtDNA, Bayesian statistical approaches have been developed to co-estimate contamination levels and call a sequence consensus deprived of mis-incorporations and other sequencing errors [52]. However, given that the number of mitochondria present in a cell varies across tissues, mtDNA-based contamination levels do not necessarily reflect the contamination levels present in the nuclear DNA [53], which should be gauged through the analysis of sexual [51,54] or autosomal [55] chromosomes.…”