Trenchevska Olgica, Phillips David A, Nelson Randall W, Nedelkov Dobrin
Molecular Biomarkers Laboratory at the Biodesign Institute, Arizona State University, Tempe, Arizona, United States of America; Intrinsic Bioprobes, Tempe, Arizona, United States of America.
Intrinsic Bioprobes, Tempe, Arizona, United States of America.
PLoS One. 2014 Jun 23;9(6):e100713. doi: 10.1371/journal.pone.0100713. eCollection 2014.
Human protein diversity arises as a result of alternative splicing, single nucleotide polymorphisms (SNPs) and posttranslational modifications. Because of these processes, each protein can exists as multiple variants in vivo. Tailored strategies are needed to study these protein variants and understand their role in health and disease. In this work we utilized quantitative mass spectrometric immunoassays to determine the protein variants concentration of beta-2-microglobulin, cystatin C, retinol binding protein, and transthyretin, in a population of 500 healthy individuals. Additionally, we determined the longitudinal concentration changes for the protein variants from four individuals over a 6 month period. Along with the native forms of the four proteins, 13 posttranslationally modified variants and 7 SNP-derived variants were detected and their concentration determined. Correlations of the variants concentration with geographical origin, gender, and age of the individuals were also examined. This work represents an important step toward building a catalog of protein variants concentrations and examining their longitudinal changes.
人类蛋白质多样性源于可变剪接、单核苷酸多态性（SNP）和翻译后修饰。由于这些过程，每种蛋白质在体内都可以以多种变体形式存在。需要定制策略来研究这些蛋白质变体，并了解它们在健康和疾病中的作用。在这项工作中，我们利用定量质谱免疫分析法测定了500名健康个体群体中β-2-微球蛋白、胱抑素C、视黄醇结合蛋白和转甲状腺素蛋白的蛋白质变体浓度。此外，我们还测定了4名个体在6个月期间蛋白质变体的纵向浓度变化。除了这四种蛋白质的天然形式外，还检测到了13种翻译后修饰变体和7种SNP衍生变体，并测定了它们的浓度。还研究了变体浓度与个体地理来源、性别和年龄的相关性。这项工作是朝着建立蛋白质变体浓度目录并研究其纵向变化迈出的重要一步。
