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A Bayesian framework for combining heterogeneous data sources for genefunction prediction (in Saccharomyces cerevisiae)

机译:用于组合基因的异构数据源的贝叶斯框架功能预测(在酿酒酵母中)

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摘要

Genomic sequencing is no longer a novelty, but gene function annotation remains a key challenge in modern biology. A variety of functional genomics experimental techniques are available, from classic methods such as affinity precipitation to advanced high-throughput techniques such as gene expression microarrays. In the future, more disparate methods will be developed, further increasing the need for integrated computational analysis of data generated by these studies. We address this problem with magic (Multisource Association of Genes by Integration of Clusters), a general framework that uses formal Bayesian reasoning to integrate heterogeneous types of high-throughput biological data (such as large-scale two-hybrid screens and multiple microarray analyses) for accurate gene function prediction. The system formally incorporates expert knowledge about relative accuracies of data sources to combine them within a normative framework. magic provides a belief level with its output that allows the user to vary the stringency of predictions. We applied magic to Saccharomyces cerevisiae genetic and physical interactions, microarray, and transcription factor binding sites data and assessed the biological relevanceof gene groupings using Gene Ontology annotations produced by theSaccaromyces Genome Database. We found that by creating functionalgroupings based on heterogeneous data types, magic improvedaccuracy of the groupings compared with microarray analysis alone. We describeseveral of the biological gene groupings identified.
机译:基因组测序已不再是一个新事物,但基因功能注释仍是现代生物学中的关键挑战。从经典方法(例如亲和沉淀)到先进的高通量技术(例如基因表达微阵列),可以使用多种功能基因组学实验技术。将来,将开发出更多不同的方法,从而进一步增加了对这些研究生成的数据进行综合计算分析的需求。我们使用魔术(集群集成的基因多源协会)解决了这个问题,魔术是使用形式贝叶斯推理来整合异构类型的高通量生物数据(例如大规模两杂交筛和多微阵列分析)的通用框架。用于准确的基因功能预测。该系统正式结合了有关数据源相对准确度的专家知识,以将它们组合到一个规范框架中。 magic通过其输出提供了一个置信度,允许用户改变预测的严格性。我们将魔术应用于酿酒酵母的遗传和物理相互作用,微阵列和转录因子结合位点数据,并评估了生物学相关性利用由基因产生的基因本体注释来进行基因分组酿酒酵母基因组数据库。我们发现通过创建功能基于异构数据类型的分组,改进了魔术与单独的微阵列分析相比,分组的准确性。我们描述确定了几个生物学基因分组。

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