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TREEGL: reverse engineering tree-evolving gene networks underlying developing biological lineages

机译:TREEGL:逆向工程发展中的生物谱系的树木进化基因网络

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摘要

>Motivation: Estimating gene regulatory networks over biological lineages is central to a deeper understanding of how cells evolve during development and differentiation. However, one challenge in estimating such evolving networks is that their host cells not only contiguously evolve, but also branch over time. For example, a stem cell evolves into two more specialized daughter cells at each division, forming a tree of networks. Another example is in a laboratory setting: a biologist may apply several different drugs individually to malignant cancer cells to analyze the effects of each drug on the cells; the cells treated by one drug may not be intrinsically similar to those treated by another, but rather to the malignant cancer cells they were derived from.>Results: We propose a novel algorithm, Treegl, an ℓ1 plus total variation penalized linear regression method, to effectively estimate multiple gene networks corresponding to cell types related by a tree-genealogy, based on only a few samples from each cell type. Treegl takes advantage of the similarity between related networks along the biological lineage, while at the same time exposing sharp differences between the networks. We demonstrate that our algorithm performs significantly better than existing methods via simulation. Furthermore we explore an application to a breast cancer dataset, and show that our algorithm is able to produce biologically valid results that provide insight into the progression and reversion of breast cancer cells.>Availability: Software will be available at .>Contact:
机译:>动机:估算生物谱系上的基因调控网络对于深入了解细胞在发育和分化过程中的进化至关重要。然而,在估计这种不断发展的网络中的一个挑战是它们的宿主细胞不仅连续地进化,而且随着时间的流逝而分支。例如,干细胞在每个分裂处演变成两个更多的专门子细胞,形成网络树。另一个例子是在实验室中:生物学家可以将几种不同的药物分别应用于恶性癌细胞,以分析每种药物对细胞的作用; >结果:我们提出了一种新颖的算法Treegl,其总和为ℓ1加变异惩罚线性回归方法,可以基于每种细胞类型的少量样本,有效地估计与通过树谱学相关的细胞类型相对应的多个基因网络。 Treegl利用了沿生物谱系的相关网络之间的相似性,同时暴露了网络之间的明显差异。通过仿真,我们证明了该算法的性能明显优于现有方法。此外,我们探索了对乳腺癌数据集的应用,并表明我们的算法能够产生生物学上有效的结果,从而洞悉乳腺癌细胞的进展和逆转。>可用性: 。>联系方式:

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