Peptide ancestry informative markers in uterine neoplasms from women of European, African, and Asian ancestry

Nicholas W Bateman; Christopher M Tarney; Tamara S Abulez; Brian L Hood; Kelly A Conrads; Ming Zhou; Anthony R Soltis; Pang-Ning Teng; Amanda Jackson; Chunqiao Tian; Clifton L Dalgard; Matthew D Wilkerson; Michael D Kessler; Zachary Goecker; Jeremy Loffredo; Craig D Shriver; Hai Hu; Michele Cote; Glendon J Parker; James Segars; Ayman Al-Hendy; John I Risinger; Neil T Phippen; Yovanni Casablanca; Kathleen M Darcy; G Larry Maxwell; Thomas P Conrads; Timothy D O'Connor

doi:10.1016/j.isci.2021.103665

Peptide ancestry informative markers in uterine neoplasms from women of European, African, and Asian ancestry

iScience. 2021 Dec 23;25(1):103665. doi: 10.1016/j.isci.2021.103665. eCollection 2022 Jan 21.

Authors

Nicholas W Bateman^{1

2

3}, Christopher M Tarney¹, Tamara S Abulez^{1

3}, Brian L Hood^{1

3}, Kelly A Conrads^{1

3}, Ming Zhou⁴, Anthony R Soltis^{3

5}, Pang-Ning Teng^{1

3}, Amanda Jackson¹, Chunqiao Tian^{1

3}, Clifton L Dalgard^{5

6}, Matthew D Wilkerson^{2

3

5

6}, Michael D Kessler⁷, Zachary Goecker⁸, Jeremy Loffredo¹, Craig D Shriver², Hai Hu^{2

9}, Michele Cote¹⁰, Glendon J Parker⁸, James Segars¹¹, Ayman Al-Hendy¹², John I Risinger¹³, Neil T Phippen^{1

2}, Yovanni Casablanca^{1

2}, Kathleen M Darcy^{1

2

3}, G Larry Maxwell^{1

2

4}, Thomas P Conrads^{1

2

4}, Timothy D O'Connor^{7

14

15}

Affiliations

¹ Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA.
² The John P. Murtha Cancer Center, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA.
³ Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., 6720A Rockledge Dr., Suite 100, Bethesda, MD 20817, USA.
⁴ Department of Obstetrics and Gynecology, Inova Fairfax Medical Campus, 3300 Gallows Road, Falls Church, VA 22042, USA.
⁵ The American Genome Center; Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
⁶ Department of Anatomy Physiology and Genetics, Uniformed Services University, 4301 Jones Bridge Road, Bethesda, MD 20814, USA.
⁷ Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
⁸ University of California, Davis, One Shields Avenue, Davis, CA 95616, USA.
⁹ Chan Soon-Shiong Institute of Molecular Medicine at Windber, Windber, PA 15963, USA.
¹⁰ Wayne State University, Detroit, MI 48202, USA.
¹¹ Johns Hopkins University Medical Center, Baltimore, MD 21218, USA.
¹² The University of Illinois College of Medicine, Chicago, IL 60612, USA.
¹³ Department of Obstetrics and Gynecology, Michigan State University, East Lansing, MI 48824, USA.
¹⁴ Program in Personalize and Genomic Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
¹⁵ Marlene and Stewart Greenebaum Comprehensive Cancer, University of Maryland School of Medicine, Baltimore, MD 21201, USA.

Abstract

Characterization of ancestry-linked peptide variants in disease-relevant patient tissues represents a foundational step to connect patient ancestry with disease pathogenesis. Nonsynonymous single-nucleotide polymorphisms encoding missense substitutions within tryptic peptides exhibiting high allele frequencies in European, African, and East Asian populations, termed peptide ancestry informative markers (pAIMs), were prioritized from 1000 genomes. In silico analysis identified that as few as 20 pAIMs can determine ancestry proportions similarly to >260K SNPs (R² = 0.99). Multiplexed proteomic analysis of >100 human endometrial cancer cell lines and uterine leiomyoma tissues combined resulted in the quantitation of 62 pAIMs that correlate with patient race and genotype-confirmed ancestry. Candidates include a D451E substitution in GC vitamin D-binding protein previously associated with altered vitamin D levels in African and European populations. pAIMs will support generalized proteoancestry assessment as well as efforts investigating the impact of ancestry on the human proteome and how this relates to the pathogenesis of uterine neoplasms.

Keywords: Genomics; Precision medicine; Proteogenomics; Proteomics.

Abstract

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