在这里，研究人员提出了约30,000个独特的蛋白质变体（Proteoform：由于单个基因的蛋白质产物有不同化学结构，可能包含遗传变异、RNA转录变异以及蛋白质修饰等导致的不同蛋白形式，故目前学术界开始用proteoform描述蛋白形态数量的总和，又可称为蛋白质变体。）的主要结构，比以前的研究多了近10倍，这些蛋白质变体由1690个人类基因表达，涉及21种细胞类型和人类血液和骨髓的血浆。
汇编在血液蛋白质变体图谱（BPA）中的结果表明，与在细胞类型中更广泛表达的相应蛋白质相比，蛋白质变体能更好的描述蛋白质水平生物学，并且是更具体的分化指标。该课题组研究人员将BPA应用在肝移植中，通过识别细胞和蛋白质变体特征来区分正常移植功能、急性排斥反应和其他移植功能障碍，从而证明了其临床应用的潜力。
据悉，人类生物学与蛋白质密切相关，但大多数测量方法并不能精确地确定选择性剪接序列或翻译后修饰。
附：英文原文
Title: The Blood Proteoform Atlas: A reference map of proteoforms in human hematopoietic cells
Author: Rafael D. Melani, Vincent R. Gerbasi, Lissa C. Anderson, Jacek W. Sikora, Timothy K. Toby, Josiah E. Hutton, David S. Butcher, Fernanda Negro, Henrique S. Seckler, Kristina Srzenti, Luca Fornelli, Jeannie M. Camarillo, Richard D. LeDuc, Anthony J. Cesnik, Emma Lundberg, Joseph B. Greer, Ryan T. Fellers, Matthew T. Robey, Caroline J. DeHart, Eleonora Forte, Christopher L. Hendrickson, Susan E. Abbatiello, Paul M. Thomas, Andy I. Kokaji, Josh Levitsky, Neil L. Kelleher
Issue&Volume: 2022-01-28
Abstract: Human biology is tightly linked to proteins, yet most measurements do not precisely determine alternatively spliced sequences or posttranslational modifications. Here, we present the primary structures of ~30,000 unique proteoforms, nearly 10 times more than in previous studies, expressed from 1690 human genes across 21 cell types and plasma from human blood and bone marrow. The results, compiled in the Blood Proteoform Atlas (BPA), indicate that proteoforms better describe protein-level biology and are more specific indicators of differentiation than their corresponding proteins, which are more broadly expressed across cell types. We demonstrate the potential for clinical application, by interrogating the BPA in the context of liver transplantation and identifying cell and proteoform signatures that distinguish normal graft function from acute rejection and other causes of graft dysfunction.
DOI: aaz5284
Source: https://www.science.org/doi/10.1126/science.aaz5284