The human plasma proteome - A nonredundant list developed by combination of four separate sources
The human plasma proteome - A nonredundant list developed by combination of four separate sources
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DOI：
10.1074/mcp.m300127-mcp200
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发表时间：
2004-04-01
影响因子：
7
通讯作者：
Lobley, A
中科院分区：
文献类型：
--
作者：
Anderson, NL;Polanski, M;Lobley, A
我们已经合并了四个不同的观点的人血浆蛋白质组，基于不同的方法，到一个单一的非冗余列表的1175个不同的基因产物。所用方法为：1）文献检索报告的血浆或血清中出现的蛋白质; 2）蛋白质的多维色谱，然后是二维电泳和质谱（MS）鉴定解析的蛋白质; 3）肽的胰蛋白酶消化和多维色谱，然后是MS鉴定;和4）来自低分子量血浆组分的肽的胰蛋白酶消化和多维层析，随后进行MS鉴定。在1,175个非冗余基因产物中，有195个包含在四个输入数据集中的一个以上。只有46个出现在所有四个。预测信号序列和跨膜结构域的发生，以及基因组本体论注释分配，允许非冗余列表的表征和数据源的比较。“非蛋白质组学”文献（468种输入蛋白质）强烈偏向于含有信号序列的细胞外蛋白质，而三种蛋白质组学方法显示出更高的细胞蛋白质代表性，包括细胞核，细胞质和驱动蛋白复合物蛋白。细胞因子和蛋白质激素几乎完全不存在于蛋白质组学数据中（可能是由于丰度低），而DNA结合蛋白等类别几乎完全不存在于文献数据中（可能是出乎意料的，因此没有寻找）。人类蛋白质组中的大多数主要类别的蛋白质都存在于血浆中，在连续更深层的分布从大部分细胞外转移到更像整个（主要是细胞）蛋白质组的分布。由此产生的非冗余列表证实了血浆和血清中存在许多感兴趣的候选标记蛋白。
We have merged four different views of the human plasma proteome, based on different methodologies, into a single nonredundant list of 1175 distinct gene products. The methodologies used were 1) literature search for proteins reported to occur in plasma or serum; 2) multidimensional chromatography of proteins followed by two-dimensional electrophoresis and mass spectroscopy ( MS) identification of resolved proteins; 3) tryptic digestion and multidimensional chromatography of peptides followed by MS identification; and 4) tryptic digestion and multidimensional chromatography of peptides from low-molecular-mass plasma components followed by MS identification. Of 1,175 nonredundant gene products, 195 were included in more than one of the four input datasets. Only 46 appeared in all four. Predictions of signal sequence and transmembrane domain occurrence, as well as Genome Ontology annotation assignments, allowed characterization of the nonredundant list and comparison of the data sources. The "nonproteomic" literature ( 468 input proteins) is strongly biased toward signal sequence-containing extracellular proteins, while the three proteomics methods showed a much higher representation of cellular proteins, including nuclear, cytoplasmic, and kinesin complex proteins. Cytokines and protein hormones were almost completely absent from the proteomics data ( presumably due to low abundance), while categories like DNA-binding proteins were almost entirely absent from the literature data ( perhaps unexpected and therefore not sought). Most major categories of proteins in the human proteome are represented in plasma, with the distribution at successively deeper layers shifting from mostly extracellular to a distribution more like the whole ( primarily cellular) proteome. The resulting nonredundant list confirms the presence of a number of interesting candidate marker proteins in plasma and serum.