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False positives complicate ancient pathogen identifications using high-throughput shotgun sequencing


Campana, Michael G; Robles García, Nelly; Rühli, Frank J; Tuross, Noreen (2014). False positives complicate ancient pathogen identifications using high-throughput shotgun sequencing. BMC Research Notes, 7:111.

Abstract

BACKGROUND Identification of historic pathogens is challenging since false positives and negatives are a serious risk. Environmental non-pathogenic contaminants are ubiquitous. Furthermore, public genetic databases contain limited information regarding these species. High-throughput sequencing may help reliably detect and identify historic pathogens. RESULTS We shotgun-sequenced 8 16th-century Mixtec individuals from the site of Teposcolula Yucundaa (Oaxaca, Mexico) who are reported to have died from the huey cocoliztli ('Great Pestilence' in Nahautl), an unknown disease that decimated native Mexican populations during the Spanish colonial period, in order to identify the pathogen. Comparison of these sequences with those deriving from the surrounding soil and from 4 precontact individuals from the site found a wide variety of contaminant organisms that confounded analyses. Without the comparative sequence data from the precontact individuals and soil, false positives for Yersinia pestis and rickettsiosis could have been reported. CONCLUSIONS False positives and negatives remain problematic in ancient DNA analyses despite the application of high-throughput sequencing. Our results suggest that several studies claiming the discovery of ancient pathogens may need further verification. Additionally, true single molecule sequencing's short read lengths, inability to sequence through DNA lesions, and limited ancient-DNA-specific technical development hinder its application to palaeopathology.

Abstract

BACKGROUND Identification of historic pathogens is challenging since false positives and negatives are a serious risk. Environmental non-pathogenic contaminants are ubiquitous. Furthermore, public genetic databases contain limited information regarding these species. High-throughput sequencing may help reliably detect and identify historic pathogens. RESULTS We shotgun-sequenced 8 16th-century Mixtec individuals from the site of Teposcolula Yucundaa (Oaxaca, Mexico) who are reported to have died from the huey cocoliztli ('Great Pestilence' in Nahautl), an unknown disease that decimated native Mexican populations during the Spanish colonial period, in order to identify the pathogen. Comparison of these sequences with those deriving from the surrounding soil and from 4 precontact individuals from the site found a wide variety of contaminant organisms that confounded analyses. Without the comparative sequence data from the precontact individuals and soil, false positives for Yersinia pestis and rickettsiosis could have been reported. CONCLUSIONS False positives and negatives remain problematic in ancient DNA analyses despite the application of high-throughput sequencing. Our results suggest that several studies claiming the discovery of ancient pathogens may need further verification. Additionally, true single molecule sequencing's short read lengths, inability to sequence through DNA lesions, and limited ancient-DNA-specific technical development hinder its application to palaeopathology.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Evolutionary Medicine
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:25 February 2014
Deposited On:27 Aug 2014 14:58
Last Modified:09 Aug 2017 06:33
Publisher:BioMed Central
ISSN:1756-0500
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1186/1756-0500-7-111
PubMed ID:24568097

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Licence: Creative Commons: Attribution 4.0 International (CC BY 4.0)

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