Automated High-Throughput Biological Sex Identification from Archeological Human Dental Enamel Using Targeted Proteomics.

Publisher: American Chemical Society Country of Publication: United States NLM ID: 101128775 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1535-3907 (Electronic) Linking ISSN: 15353893 NLM ISO Abbreviation: J Proteome Res Subsets: MEDLINE

Original Publication: Washington, D.C. : American Chemical Society, c2002-

Proteomics*/methods ; Dental Enamel*/chemistry ; Sex Determination Analysis*/methods; Humans ; Male ; Female ; Chromatography, Liquid/methods ; Mass Spectrometry/methods ; Archaeology/methods

Biological sex is key information for archeological and forensic studies, which can be determined by proteomics. However, the lack of a standardized approach for fast and accurate sex identification currently limits the reach of proteomics applications. Here, we introduce a streamlined mass spectrometry (MS)-based workflow for the determination of biological sex using human dental enamel. Our approach builds on a minimally invasive sampling strategy by acid etching, a rapid online liquid chromatography (LC) gradient coupled to a high-resolution parallel reaction monitoring (PRM) assay allowing for a throughput of 200 samples per day (SPD) with high quantitative performance enabling confident identification of both males and females. Additionally, we developed a streamlined data analysis pipeline and integrated it into a Shiny interface for ease of use. The method was first developed and optimized using modern teeth and then validated in an independent set of deciduous teeth of known sex. Finally, the assay was successfully applied to archeological material, enabling the analysis of over 300 individuals. We demonstrate unprecedented performance and scalability, speeding up MS analysis by 10-fold compared to conventional proteomics-based sex identification methods. This work paves the way for large-scale archeological or forensic studies enabling the investigation of entire populations rather than focusing on individual high-profile specimens. Data are available via ProteomeXchange with the identifier PXD049326.

J Clin Endocrinol Metab. 2009 May;94(5):1638-43. (PMID: 19258406)
Nature. 2024 Jan;625(7996):735-742. (PMID: 38030727)
Proc Natl Acad Sci U S A. 2020 Sep 8;117(36):21847-21848. (PMID: 32817483)
Nat Methods. 2007 Sep;4(9):709-12. (PMID: 17721543)
Sci Rep. 2023 Jul 6;13(1):9594. (PMID: 37414858)
J Proteome Res. 2017 Feb 3;16(2):712-719. (PMID: 27997202)
Mol Cell Proteomics. 2015 Sep;14(9):2301-7. (PMID: 26217018)
Sci Rep. 2014 Nov 27;4:7104. (PMID: 25429530)
Sci Rep. 2020 Sep 2;10(1):14427. (PMID: 32879376)
Int J Mol Sci. 2015 Dec 02;16(12):28566-81. (PMID: 26633379)
Nat Commun. 2022 May 5;13(1):2458. (PMID: 35513387)
R Soc Open Sci. 2020 Jan 22;7(1):191172. (PMID: 32218948)
Proc Natl Acad Sci U S A. 2017 Dec 26;114(52):13649-13654. (PMID: 29229823)
Anal Chem. 1995 Apr 15;67(8):1426-36. (PMID: 7741214)
PLoS One. 2022 Jul 27;17(7):e0270040. (PMID: 35895633)
Int J Legal Med. 2021 Jul;135(4):1351-1358. (PMID: 33903958)
J Mol Diagn. 2004 Nov;6(4):401-5. (PMID: 15507681)
Mol Cell Proteomics. 2018 Nov;17(11):2284-2296. (PMID: 30104208)
Proc Biol Sci. 2021 Jul 14;288(1954):20210020. (PMID: 34229485)
Nat Commun. 2018 Oct 3;9(1):4064. (PMID: 30283003)
Mol Ecol Resour. 2021 Aug;21(6):1808-1819. (PMID: 33720532)
Mol Cell Proteomics. 2020 Jul;19(7):1088-1103. (PMID: 32312845)
Ann Hum Biol. 2006 Mar-Apr;33(2):227-40. (PMID: 16684695)
Nat Commun. 2017 Aug 21;8(1):291. (PMID: 28827567)
Mol Syst Biol. 2008;4:222. (PMID: 18854821)
Sci Adv. 2023 May 24;9(21):eade7686. (PMID: 37224244)
Proc Natl Acad Sci U S A. 2022 Oct 25;119(43):e2109326119. (PMID: 35609205)
J Proteome Res. 2011 Apr 1;10(4):1785-93. (PMID: 21309581)
Nature. 2019 Oct;574(7776):103-107. (PMID: 31511700)
Mol Cell Proteomics. 2012 Jun;11(6):O111.016717. (PMID: 22261725)
PLoS Genet. 2011 Mar;7(3):e1001342. (PMID: 21436896)
J Proteome Res. 2011 Apr 1;10(4):1794-805. (PMID: 21254760)
Mol Syst Biol. 2018 Aug 13;14(8):e8126. (PMID: 30104418)
Proteomics. 2016 Aug;16(15-16):2146-59. (PMID: 27145088)
Proc Natl Acad Sci U S A. 2003 Apr 1;100(7):4060-5. (PMID: 12646701)
Am J Phys Anthropol. 2021 Nov;176(3):528-535. (PMID: 34382686)
Proteomics. 2019 Mar;19(5):e1800341. (PMID: 30650255)
Am J Phys Anthropol. 2017 Dec;164(4):853-860. (PMID: 28884802)
Sci Rep. 2019 Sep 11;9(1):13130. (PMID: 31511583)
Elife. 2016 Sep 27;5:. (PMID: 27668515)
Nat Protoc. 2016 Dec;11(12):2301-2319. (PMID: 27809316)
Archaeol Anthropol Sci. 2020;12(11):265. (PMID: 33123298)
Nat Commun. 2018 Nov 20;9(1):4744. (PMID: 30459334)
Mol Cell Proteomics. 2012 Dec;11(12):1709-23. (PMID: 22962056)
Nature. 2019 Dec;576(7786):262-265. (PMID: 31723270)
J Proteomics. 2020 Jan 16;211:103548. (PMID: 31626997)
Gene. 1995 Dec 29;167(1-2):327-32. (PMID: 8566801)
Bioinformatics. 2010 Apr 1;26(7):966-8. (PMID: 20147306)
Hum Mol Genet. 2007 Feb 1;16(3):307-16. (PMID: 17189292)
Forensic Sci Int. 2016 Apr;261:165.e1-8. (PMID: 26926105)
Anal Bioanal Chem. 2022 Feb;414(4):1723-1737. (PMID: 34977977)
Nature. 2020 Apr;580(7802):235-238. (PMID: 32269345)
Mol Cell Proteomics. 2017 Dec;16(12):2296-2309. (PMID: 29070702)
Mass Spectrom Rev. 2020 May;39(3):229-244. (PMID: 28691345)
Mol Cell Proteomics. 2012 Nov;11(11):1475-88. (PMID: 22865924)
Nucleic Acids Res. 2022 Jan 7;50(D1):D543-D552. (PMID: 34723319)
Angew Chem Int Ed Engl. 2018 Jun 18;57(25):7369-7374. (PMID: 29603563)
Sci Adv. 2020 Nov 4;6(45):. (PMID: 33148651)
Nat Commun. 2018 Dec 3;9(1):5128. (PMID: 30510204)

Keywords: archeology; biological sex; dental enamel; forensics; high-throughput; palaeoproteomics; parallel reaction monitoring (PRM); proteomics

Date Created: 20240926 Date Completed: 20241101 Latest Revision: 20241107

20241107

PMC11536428

10.1021/acs.jproteome.4c00557

39324540