Integrated pathway clusters with coherent biological themes for target prioritisation.

Integrated pathway clusters with coherent biological themes for target prioritisation.
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DOI:
10.1371/journal.pone.0099030
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Mizuguchi K
Mizuguchi K
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Chen YA;Tripathi LP;Dessailly BH;Nyström-Persson J;Ahmad S;Mizuguchi K

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为进一步的实验表征确定候选基因的优先顺序是生物医学研究中一项重要但具有挑战性的任务。实现这一目标的一种方法是识别在感兴趣的基因组中富集的特定生物学主题,以获得对所研究的生物学现象的见解。生物学途径数据在鉴定基因和/或基因组的功能关联方面特别有用。然而,在不同的知识库中编译的生物途径信息在范围和内容上往往不同,这妨碍了对基因集进行更有效和全面的表征。在这里,我们描述了一种新的方法来构建生物连贯的基因集的途径数据在主要的公共知识库,并利用它们的功能分析的大基因集。我们首先揭示了不同途径之间的基因内容的显着重叠,然后定义了一个聚类方法的基础上共享的基因内容和基因重叠模式的相似性。我们使用独立的定量测量建立了构建的通路簇的生物相关性,并且我们最终证明了构建的通路簇在从文献中收集的与多种人类疾病相关的基因集的比较功能富集分析中的有效性。通路簇和基因映射已被集成到TargetMine数据仓库中,并可能提供一种简洁,可管理和生物相关的基因集功能分析方法,并促进候选基因的优先排序。
Prioritising candidate genes for further experimental characterisation is an essential, yet challenging task in biomedical research. One way of achieving this goal is to identify specific biological themes that are enriched within the gene set of interest to obtain insights into the biological phenomena under study. Biological pathway data have been particularly useful in identifying functional associations of genes and/or gene sets. However, biological pathway information as compiled in varied repositories often differs in scope and content, preventing a more effective and comprehensive characterisation of gene sets. Here we describe a new approach to constructing biologically coherent gene sets from pathway data in major public repositories and employing them for functional analysis of large gene sets. We first revealed significant overlaps in gene content between different pathways and then defined a clustering method based on the shared gene content and the similarity of gene overlap patterns. We established the biological relevance of the constructed pathway clusters using independent quantitative measures and we finally demonstrated the effectiveness of the constructed pathway clusters in comparative functional enrichment analysis of gene sets associated with diverse human diseases gathered from the literature. The pathway clusters and gene mappings have been integrated into the TargetMine data warehouse and are likely to provide a concise, manageable and biologically relevant means of functional analysis of gene sets and to facilitate candidate gene prioritisation.
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