autosome a clustering method for identifying gene expression modules without prior knowledge of cluster number常染色体基因表达聚类方法确定模块没有先验知识集群数量.pdfVIP

Newman and Cooper BMC Bioinformatics 2010, 11:117 /1471-2105/11/117 METHODOLOGY ARTICLE Open Access AutoSOME: a clustering method for identifying gene expression modules without prior knowledge of cluster number 1 1,2* Aaron M Newman , James B Cooper Abstract Background: Clustering the information content of large high-dimensional gene expression datasets has widespread application in “omics” biology. Unfortunately, the underlying structure of these natural datasets is often fuzzy, and the computational identification of data clusters generally requires knowledge about cluster number and geometry. Results: We integrated strategies from machine learning, cartography, and graph theory into a new informatics method for automatically clustering self-organizing map ensembles of high-dimensional data. Our new method, called AutoSOME, readily identifies discrete and fuzzy data clusters without prior knowledge of cluster number or structure in diverse datasets including whole genome microarray data. Visualization of AutoSOME output using network diagrams and differential heat maps reveals unexpected variation among well-characterized cancer cell lines. Co-expression analysis of data from human embryonic and induced pluripotent stem cells using AutoSOME identifies 3400 up-regulated genes associated with pluripotency, and indicates that a recently identified protein- protein interaction network characterizing pluripotency was underestimated by a factor of four. Conclusions: By effectively extracting important information from high-dimensional microarray data without prior knowledge or the need for data filtration, AutoSOME can yield systems-level insights from whole genome microarray expression studies. Due to its generality, this new method should also have practical utility for a