A data-mining approach to rank candidate protein-binding partners-The case of biogenesis of lysosome-related organelles complex-1 (BLOC-1).
A data-mining approach to rank candidate protein-binding partners-The case of biogenesis of lysosome-related organelles complex-1 (BLOC-1).
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DOI：
10.1007/s10545-008-1014-7
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发表时间：
2009-04
影响因子：
4.2
通讯作者：
Dell'Angelica, E. C.
中科院分区：
文献类型：
--
作者：
Rodriguez-Fernandez, I. A.;Dell'Angelica, E. C.
蛋白质-蛋白质相互作用的研究是揭示与人类疾病相关的基因产物分子功能的有力方法。由于相互作用组学项目，蛋白质-蛋白质相互作用数据正在以前所未有的速度积累，尽管已经认识到这些数据中的很大一部分可能代表假阳性。在我们对溶酶体相关细胞器复合物-1（BLOC-1）的生物发生的研究中，我们面临着有太多候选结合伴侣的问题，无法进行实验。BLOC-1是一种参与蛋白质运输并含有Hermansky-Pudlak综合征中突变基因产物的蛋白质复合物。在这项工作中，我们已经探索了有效地收集高质量的候选结合伙伴的信息，并以视觉友好的方式呈现信息的方法。我们应用该方法对70个候选人BLOC-1结合伴侣和102个候选人果蝇BLOC-1结合伴侣进行了排序。人BLOC-1的最佳候选者是由RAB 11 A基因编码的小GTdR，其是哺乳动物中Rab 38和Rab 32蛋白以及苍蝇中lightoid基因产物的paramentary。有趣的是，D. melanogaster发现了Rab 11和lightoid之间的合成致病/致死相互作用。可以定制本文所述的数据挖掘方法，以研究其他蛋白质的候选结合配偶体或来源于其他类型的“组学”数据的可能候选物。
The study of protein-protein interactions is a powerful approach to uncover the molecular function of gene products associated with human disease. Protein-protein interaction data are accumulating at an unprecedented pace owing to interactomics projects, although it has been recognized that a significant fraction of these data likely represents false positives. During our studies of Biogenesis of Lysosome-related Organelles Complex-1 (BLOC-1), a protein complex involved in protein trafficking and containing the products of genes mutated in Hermansky-Pudlak syndrome, we faced the problem of having too many candidate binding partners to pursue experimentally. In this work, we have explored ways of efficiently gathering high-quality information about candidate binding partners and presenting the information in a visually friendly manner. We applied the approach to rank 70 candidate binding partners of human BLOC-1 and 102 candidates of its counterpart from Drosophila melanogaster. The top candidate for human BLOC-1 was the small GTPase encoded by the RAB11A gene, which is a paralog of the Rab38 and Rab32 proteins in mammals and the lightoid gene product in flies. Interestingly, genetic analyses in D. melanogaster uncovered a synthetic sick/lethal interaction between Rab11 and lightoid. The data-mining approach described herein can be customized to study candidate binding partners for other proteins or possibly candidates derived from other types of “omics” data.
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