Novel Bioinformatics-Based Approach for Proteomic Biomarkers Prediction of Calpain-2 &Caspase-3 Protease Fragmentation: Application to βII-Spectrin Protein.
Novel Bioinformatics-Based Approach for Proteomic Biomarkers Prediction of Calpain-2 &Caspase-3 Protease Fragmentation: Application to βII-Spectrin Protein.
复制标题
基于新型生物信息学的方法，用于蛋白质组学生物标志物预测Calpain-2和caspase-3蛋白酶碎片化：应用于βII-光谱蛋白。
DOI：
10.1038/srep41039
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发表时间：
2017-01-23
影响因子：
4.6
通讯作者：
Kobeissy F
中科院分区：
文献类型：
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作者：
El-Assaad A;Dawy Z;Nemer G;Kobeissy F
随着降解学学科的发展，蛋白酶的关键生物学作用已经显现出来，这些学科涉及到确定蛋白酶/底物，从而产生可用作与不同生物学-临床意义相关的假定生物标志物的分解产物(BDP)。在肿瘤生物学领域，基质金属蛋白酶(MMPs)产生的蛋白BDPs指示癌症的恶性生长，而在神经损伤领域，Calain-2和Caspase-3蛋白产生的BDPs片段指示不同损伤情况下不同的神经细胞死亡机制。先进的蛋白质组学技术在实验鉴定这些BDP方面取得了显着的进展。在这项工作中，我们提出了一种基于生物信息学的预测方法，能够高精度和高效率地识别与蛋白酶相关的BDP。该方法利用最先进的序列匹配和比对算法。它首先在任何一组蛋白质底物中定位一致的序列出现及其变体，产生所有由切割产生的片段。复杂性存在于O(Mn)空间和O(NMN)时间，其中N、m和n分别是蛋白质序列的数目、共有序列的长度和每个蛋白质序列的长度。最后，将所提出的方法与脑损伤确认的生物标志物βII-SPECTIN蛋白进行对比验证。
The crucial biological role of proteases has been visible with the development of degradomics discipline involved in the determination of the proteases/substrates resulting in breakdown-products (BDPs) that can be utilized as putative biomarkers associated with different biological-clinical significance. In the field of cancer biology, matrix metalloproteinases (MMPs) have shown to result in MMPs-generated protein BDPs that are indicative of malignant growth in cancer, while in the field of neural injury, calpain-2 and caspase-3 proteases generate BDPs fragments that are indicative of different neural cell death mechanisms in different injury scenarios. Advanced proteomic techniques have shown a remarkable progress in identifying these BDPs experimentally. In this work, we present a bioinformatics-based prediction method that identifies protease-associated BDPs with high precision and efficiency. The method utilizes state-of-the-art sequence matching and alignment algorithms. It starts by locating consensus sequence occurrences and their variants in any set of protein substrates, generating all fragments resulting from cleavage. The complexity exists in space O(mn) as well as in O(Nmn) time, where N, m, and n are the number of protein sequences, length of the consensus sequence, and length per protein sequence, respectively. Finally, the proposed methodology is validated against βII-spectrin protein, a brain injury validated biomarker.