Reconstructing differentiation networks and their regulation from time series single-cell expression data.

Reconstructing differentiation networks and their regulation from time series single-cell expression data.
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DOI:
10.1101/gr.225979.117
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发表时间:
2018-03-01
期刊:
影响因子:
7
通讯作者:
Bar-Joseph Z
Bar-Joseph Z
中科院分区:
生物学1区
文献类型:
--
作者:
Ding J;Aronow BJ;Kaminski N;Kitzmiller J;Whitsett JA;Bar-Joseph Z

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使用单细胞RNA-seq数据生成详细和准确的器官发生模型仍然是一个主要挑战。目前的方法主要依赖于后代细胞在基因表达水平方面与其亲本相似的假设。这些假设并不总是适用于体内研究,体内研究通常包括不频繁采样、不同步和不同的细胞群。因此,可能需要额外的信息来确定祖细胞的正确顺序和分支以及在器官发生的早期阶段活跃的转录因子(tf)集。为了实现这样的建模,我们开发了一种方法,该方法学习了一个概率模型,该模型集成了表达相似性和调控信息,以重建动态发育的细胞轨迹。当应用于小鼠肺发育数据时,该方法可以准确区分不同的细胞类型和谱系。现有的和新的实验数据验证了该方法识别细胞命运关键调节因子的能力。
Generating detailed and accurate organogenesis models using single-cell RNA-seq data remains a major challenge. Current methods have relied primarily on the assumption that descendant cells are similar to their parents in terms of gene expression levels. These assumptions do not always hold for in vivo studies, which often include infrequently sampled, unsynchronized, and diverse cell populations. Thus, additional information may be needed to determine the correct ordering and branching of progenitor cells and the set of transcription factors (TFs) that are active during advancing stages of organogenesis. To enable such modeling, we have developed a method that learns a probabilistic model that integrates expression similarity with regulatory information to reconstruct the dynamic developmental cell trajectories. When applied to mouse lung developmental data, the method accurately distinguished different cell types and lineages. Existing and new experimental data validated the ability of the method to identify key regulators of cell fate.
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