Serrano-Solano Beatriz, Díaz Ramos Antonio, Hériché Jean-Karim, Ranea Juan A G
Department of Molecular Biology and Biochemistry, University of Málaga, Boulevard Louis Pasteur, Málaga, 29071, Spain.
Department of Algebra, Geometry and Topology, University of Málaga, Boulevard Louis Pasteur, Málaga, 29071, Spain.
BMC Bioinformatics. 2017 Feb 10;18(1):96. doi: 10.1186/s12859-017-1503-5.
Loss-of-function phenotypes are widely used to infer gene function using the principle that similar phenotypes are indicative of similar functions. However, converting phenotypic to functional annotations requires careful interpretation of phenotypic descriptions and assessment of phenotypic similarity. Understanding how functions and phenotypes are linked will be crucial for the development of methods for the automatic conversion of gene loss-of-function phenotypes to gene functional annotations.
We explored the relation between cellular phenotypes from RNAi-based screens in human cells and gene annotations of cellular functions as provided by the Gene Ontology (GO). Comparing different similarity measures, we found that information content-based measures of phenotypic similarity were the best at capturing gene functional similarity. However, phenotypic similarities did not map to the Gene Ontology organization of gene function but to functions defined as groups of GO terms with shared gene annotations.
Our observations have implications for the use and interpretation of phenotypic similarities as a proxy for gene functions both in RNAi screen data analysis and curation and in the prediction of disease genes.
功能丧失型表型被广泛用于依据相似表型指示相似功能的原理来推断基因功能。然而，将表型转化为功能注释需要对表型描述进行仔细解读并评估表型相似性。理解功能与表型之间的联系对于开发将基因功能丧失型表型自动转化为基因功能注释的方法至关重要。
我们探究了基于RNA干扰的人类细胞筛选中的细胞表型与基因本体论（GO）提供的细胞功能基因注释之间的关系。比较不同的相似性度量方法，我们发现基于信息内容的表型相似性度量方法在捕捉基因功能相似性方面表现最佳。然而，表型相似性并非映射到基因功能的基因本体论组织，而是映射到定义为具有共享基因注释的GO术语组的功能。
我们的观察结果对于在RNA干扰筛选数据分析与管理以及疾病基因预测中使用和解释表型相似性作为基因功能的替代指标具有启示意义。
