@article{6d82f1566ac44c03a4d8bafa8dad5bff,
title = "Peptide ancestry informative markers in uterine neoplasms from women of European, African, and Asian ancestry",
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",
author = "Bateman, {Nicholas W.} and Tarney, {Christopher M.} and Abulez, {Tamara S.} and Hood, {Brian L.} and Conrads, {Kelly A.} and Ming Zhou and Soltis, {Anthony R.} and Teng, {Pang Ning} and Amanda Jackson and Chunqiao Tian and Dalgard, {Clifton L.} and Wilkerson, {Matthew D.} and Kessler, {Michael D.} and Zachary Goecker and Jeremy Loffredo and Shriver, {Craig D.} and Hai Hu and Michele Cote and Parker, {Glendon J.} and James Segars and Ayman Al-Hendy and Risinger, {John I.} and Phippen, {Neil T.} and Yovanni Casablanca and Darcy, {Kathleen M.} and Maxwell, {G. Larry} and Conrads, {Thomas P.} and O'Connor, {Timothy D.}",
note = "Funding Information: This study was supported in part by the U.S. Department of Defense - Uniformed Services University of the Health Sciences (HU0001-16-2-0006 and HU0001-16-2-0014). The authors would like to thank Tracy Litzi, BS; Glenn Gist, BS; Julie Oliver, MS; Dave Mitchell, MS; Domenic Tommarello, MS; and Wei Ao, BS for their technical contributions as well as Albert Dobi, PhD; Gyorgi Petrovics, PhD; and Sara Scannell, BS for critical review of this manuscript. Contributed to conception: N.W.B. T.D.O. T.P.C. G.L.M. Contributed to experimental design: N.W.B. T.D.O. T.P.C. Contributed to data acquisition, analysis, and/or interpretation of data: N.W.B. T.D.O. C.M.T. T.S.A. B.L.H. K.A.C. M.Z. P.T. A.R.S. A.J. Z.G. J.L. C.T. C.L.D. M.D.W. Drafted and/or revised the article: N.W.B. T.D.O. A.R.S. M.D.K. C.D.S. H.H. M.C. G.J.P. J.S. A.A.-H. J.R.R. N.T.P. Y.C. K.M.D. T.P.C. G.L.M. Acquired funding for the research: Y.C. G.L.M. All authors read and approved the final manuscript. G.L.M. is a consultant for Kiyatec, GSK, and Merck. T.P.C. is a ThermoFisher Scientific, Inc SAB member and receives research funding from AbbVie. G.J.P. has received a patent based on concepts presented in this study (US 8,877,455 B2, Australian Patent 2011229918, Canadian Patent CA 2794248, and European Patent EP11759843.3). Funding Information: This study was supported in part by the U.S. Department of Defense - Uniformed Services University of the Health Sciences ( HU0001-16-2-0006 and HU0001-16-2-0014 ). The authors would like to thank Tracy Litzi, BS; Glenn Gist, BS; Julie Oliver, MS; Dave Mitchell, MS; Domenic Tommarello, MS; and Wei Ao, BS for their technical contributions as well as Albert Dobi, PhD; Gyorgi Petrovics, PhD; and Sara Scannell, BS for critical review of this manuscript. Funding Information: G.L.M. is a consultant for Kiyatec, GSK, and Merck. T.P.C. is a ThermoFisher Scientific, Inc SAB member and receives research funding from AbbVie. G.J.P. has received a patent based on concepts presented in this study (US 8,877,455 B2, Australian Patent 2011229918, Canadian Patent CA 2794248, and European Patent EP11759843.3). Publisher Copyright: {\textcopyright} 2021 The Author(s)",
year = "2022",
month = jan,
day = "21",
doi = "10.1016/j.isci.2021.103665",
language = "English",
volume = "25",
journal = "iScience",
issn = "2589-0042",
number = "1",
}