Comprehensive Genome-Wide Proteomic Analysis of Human Placental Tissue for the Chromosome-Centric Human Proteome Project

As a starting point of the Chromosome-Centric Human Proteome
Project
(C-HPP), we established strategies of genome-wide proteomic analysis,
including protein identification, quantitation of disease-specific
proteins, and assessment of post-translational modifications, using
paired human placental tissues from healthy and preeclampsia patients.
This analysis resulted in identification of 4239 unique proteins with
high confidence (two or more unique peptides with a false discovery
rate less than 1%), covering 21% of approximately 20 059 (Ensembl
v69, Oct 2012) human proteins, among which 28 proteins exhibited differentially
expressed preeclampsia-specific proteins. When these proteins are
assigned to all human chromosomes, the pattern of the newly identified
placental protein population is proportional to that of the gene count
distribution of each chromosome. We also identified 219 unique N-linked glycopeptides, 592 unique phosphopeptides, and
66 chromosome 13-specific proteins. In particular, protein evidence
of 14 genes previously known to be specifically up-regulated in human
placenta was verified by mass spectrometry. With respect to the functional
implication of these proteins, 38 proteins were found to be involved
in regulatory factor biosynthesis or the immune system in the placenta,
but the molecular mechanism of these proteins during pregnancy warrants
further investigation. As far as we know, this work produced the highest
number of proteins identified in the placenta and will be useful for
annotating and mapping all proteins encoded in the human genome.

作为染色体为中心的人类蛋白质组计划（Chromosome-Centric Human Proteome Project, C-HPP）的开篇研究，我们采用健康个体与子痫前期患者的配对胎盘组织，建立了全基因组蛋白质组分析策略，涵盖蛋白质鉴定、疾病特异性蛋白定量以及翻译后修饰评估三大方向。本次分析以高置信度鉴定出4239种独特蛋白质（满足至少2条独特肽段且错误发现率低于1%），覆盖了20059个人类蛋白（Ensembl v69，2012年10月）中的21%，其中28种为子痫前期特异性差异表达蛋白。当将这些蛋白定位至全部人类染色体时，新鉴定的胎盘蛋白群体的分布模式与各染色体的基因计数分布呈显著正相关。我们还鉴定出219种独特的N-连接糖肽、592种独特磷酸肽，以及66种13号染色体特异性蛋白。尤为值得一提的是，本研究通过质谱验证了此前已知的14种在人胎盘中特异性高表达的基因对应的蛋白质证据。针对这些蛋白的功能意义，研究发现38种蛋白参与胎盘内调节因子生物合成或免疫系统调控，但这些蛋白在妊娠过程中的分子机制仍有待进一步探究。据我们所知，本研究是目前胎盘组织中鉴定蛋白数量最多的相关工作，将为人类基因组编码的全部蛋白质的注释与图谱绘制提供重要支撑。