A human phenome-interactome network of protein complexes implicated in genetic disorders
A human phenome-interactome network of protein complexes implicated in genetic disorders
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DOI：
10.1038/nbt1295
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发表时间：
2007-03-01
影响因子：
46.9
通讯作者：
Brunak, Soren
中科院分区：
文献类型：
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作者：
Lage, Kasper;Karlberg, E. Olof;Brunak, Soren
我们对人类蛋白质复合物进行了系统的大规模分析，这些蛋白质复合物包含与许多不同类别的人类疾病有关的基因产物，以创建一个表型相互作用组网络。这是通过将人类蛋白质的质量控制相互作用与经验证的、计算得出的表型相似性评分相结合来完成的，从而允许鉴定可能与疾病相关的先前未知的复合物。使用与人类疾病相关的蛋白质复合物的表型排名，我们开发了贝叶斯预测器，在669个连锁区间中的298个中，正确地将已知的致病蛋白质列为首选候选物，并且在870个没有确定致病基因的区间中，提供了与色素性视网膜炎，上皮性卵巢癌，炎症性肠病，肌萎缩性侧索硬化症，阿尔茨海默病、2型糖尿病和冠心病。我们公开的与病理学相关的蛋白质复合物草案包括506个复合物，这些复合物揭示了疾病促进基因之间的功能关系，这将为未来的实验提供信息。
We performed a systematic, large-scale analysis of human protein complexes comprising gene products implicated in many different categories of human disease to create a phenome-interactome network. This was done by integrating quality-controlled interactions of human proteins with a validated, computationally derived phenotype similarity score, permitting identification of previously unknown complexes likely to be associated with disease. Using a phenomic ranking of protein complexes linked to human disease, we developed a Bayesian predictor that in 298 of 669 linkage intervals correctly ranks the known disease-causing protein as the top candidate, and in 870 intervals with no identified disease-causing gene, provides novel candidates implicated in disorders such as retinitis pigmentosa, epithelial ovarian cancer, inflammatory bowel disease, amyotrophic lateral sclerosis, Alzheimer disease, type 2 diabetes and coronary heart disease. Our publicly available draft of protein complexes associated with pathology comprises 506 complexes, which reveal functional relationships between disease-promoting genes that will inform future experimentation.