The statistical geometry of transcriptome divergence in cell-type evolution and cancer
The statistical geometry of transcriptome divergence in cell-type evolution and cancer
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DOI：
10.1038/ncomms7066
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发表时间：
2015-01-01
影响因子：
16.6
通讯作者：
Wagner, Guenter P.
中科院分区：
文献类型：
--
作者：
Liang, Cong;Forrest, Alistair R. R.;Wagner, Guenter P.
在进化过程中，由于个体细胞类型数量的增加，身体计划的复杂性也随之增加。然而，人们对产生这种有机体复杂性的机制知之甚少。新细胞类型起源的一种模型是姐妹细胞类型模型。根据该模型，每种细胞类型都通过祖先细胞类型的特化与姐妹细胞类型一起产生。姐妹细胞类型模型的一个关键预测是细胞类型的基因表达谱呈现树结构。在这里，我们提出了一种统计模型，用于检测转录组数据中的树结构，并将其应用于来自 ENCODE 和 FANTOM5 的转录组。我们发现正常细胞的转录组具有大量的层次结构。相比之下，癌细胞系的树结构较少，这表明癌细胞的出现遵循与进化细胞类型起源不同的原则。
In evolution, body plan complexity increases due to an increase in the number of individualized cell types. Yet, there is very little understanding of the mechanisms that produce this form of organismal complexity. One model for the origin of novel cell types is the sister cell-type model. According to this model, each cell type arises together with a sister cell type through specialization from an ancestral cell type. A key prediction of the sister cell-type model is that gene expression profiles of cell types exhibit tree structure. Here we present a statistical model for detecting tree structure in transcriptomic data and apply it to transcriptomes from ENCODE and FANTOM5. We show that transcriptomes of normal cells harbour substantial amounts of hierarchical structure. In contrast, cancer cell lines have less tree structure, suggesting that the emergence of cancer cells follows different principles from that of evolutionary cell-type origination.