Massjouni Naveed, Rivera Corban G, Murali T M
660 McBryde Hall, Department of Computer Science, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA.
Nucleic Acids Res. 2006 Jul 1;34(Web Server issue):W340-4. doi: 10.1093/nar/gkl225.
Dramatic advances in sequencing technology and sophisticated experimental assays that interrogate the cell, combined with the public availability of the resulting data, herald the era of systems biology. However, the biological functions of more than 40% of the genes in sequenced genomes are unknown, posing a fundamental barrier to progress in systems biology. The large scale and diversity of available data requires the development of techniques that can automatically utilize these datasets to make quantified and robust predictions of gene function that can be experimentally verified. We present a service called the VIRtual Gene Ontology (VIRGO) that (i) constructs a functional linkage network (FLN) from gene expression and molecular interaction data, (ii) labels genes in the FLN with their functional annotations in the Gene Ontology and (iii) systematically propagates these labels across the FLN in order to precisely predict the functions of unlabelled genes. VIRGO assigns confidence estimates to predicted functions so that a biologist can prioritize predictions for further experimental study. For each prediction, VIRGO also provides an informative 'propagation diagram' that traces the flow of information in the FLN that led to the prediction. VIRGO is available at http://whipple.cs.vt.edu:8080/virgo.
测序技术的巨大进步以及用于深入研究细胞的复杂实验分析方法,再加上所得数据的公开可得性,预示着系统生物学时代的到来。然而,已测序基因组中超过40%的基因的生物学功能尚不清楚,这对系统生物学的进展构成了根本性障碍。现有数据的规模和多样性要求开发能够自动利用这些数据集来对基因功能进行量化且可靠的预测(并可通过实验验证)的技术。我们提出了一种名为虚拟基因本体(VIRGO)的服务,它(i)从基因表达和分子相互作用数据构建功能联系网络(FLN),(ii)用基因本体中的功能注释标记FLN中的基因,并且(iii)在FLN中系统地传播这些标签,以便精确预测未标记基因的功能。VIRGO为预测的功能赋予置信度估计值,从而使生物学家能够对预测进行优先级排序以用于进一步的实验研究。对于每个预测,VIRGO还提供一个信息丰富的“传播图”,该图追踪导致该预测的FLN中的信息流。可通过http://whipple.cs.vt.edu:8080/virgo访问VIRGO。