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首页> 外文期刊>Biomedical Engineering and Computational Biology >Application of a Bioinformatics-Based Approach to Identify Novel Putative in vivo BACE1 Substrates:
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Application of a Bioinformatics-Based Approach to Identify Novel Putative in vivo BACE1 Substrates:

机译：基于生物信息学的方法在鉴定新型假定的体内BACE1底物中的应用：

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BACE1, a membrane-bound aspartyl protease that is implicated in Alzheimer's disease, is the first protease to cut the amyloid precursor protein resulting in the generation of amyloid-β and its aggregation to form senile plaques, a hallmark feature of the disease. Few other native BACE1 substrates have been identified despite its relatively loose substrate specificity. We report a bioinformatics approach identifying several putative BACE1 substrates. Using our algorithm, we successfully predicted the cleavage sites for 70% of known BACE1 substrates and further validated our algorithm output against substrates identified in a recent BACE1 proteomics study that also showed a 70% success rate. Having validated our approach with known substrates, we report putative cleavage recognition sequences within 962 proteins, which can be explored using in vivo methods. Approximately 900 of these proteins have not been identified or implicated as BACE1 substrates. Gene ontology cluster analysis of the putative substrates identified enrichment in proteins involved in immune system processes and in cell surface protein-protein interactions.
机译：BACE1是与阿尔茨海默氏病有关的膜结合天冬氨酰蛋白酶，是第一种切割淀粉样前体蛋白的蛋白酶，可导致淀粉样β的生成及其聚集形成老年斑，这是该病的标志性特征。尽管底物特异性相对较弱，但几乎没有其他天然BACE1底物被鉴定出来。我们报告了一种生物信息学方法，确定了几种假定的BACE1底物。使用我们的算法，我们成功地预测了70％的已知BACE1底物的切割位点，并针对最近在BACE1蛋白质组学研究中鉴定出的底物进一步验证了我们的算法输出，该研究也显示出70％的成功率。用已知的底物验证了我们的方法后，我们报告了962种蛋白质中的假定切割识别序列，可以使用体内方法进行探索。这些蛋白质中大约有900种尚未被鉴定或与BACE1底物有关。假定的底物的基因本体簇分析确定了参与免疫系统过程和细胞表面蛋白质-蛋白质相互作用的蛋白质的富集。

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