Inferring causal phenotype networks from segregating populations

Inferring causal phenotype networks from segregating populations
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DOI:
10.1534/genetics.107.085167
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发表时间:
2008-06-01
期刊:
影响因子:
3.3
通讯作者:
Yandell, Brian S.
Yandell, Brian S.
中科院分区:
生物学2区
文献类型:
--
作者:
Neto, Elias Chaibub;Ferrara, Christine T.;Yandell, Brian S.

文献摘要

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复杂性状研究的一个主要目标是解读相关表型之间的因果相互关系。当前的方法大多产生无方向的网络,这些网络连接表型但没有因果方向。由于非因果的偏相关,其中一些连接可能是虚假的。我们展示了如何通过为每个表型纳入因果数量性状位点(QTL),在一个无方向的表型网络中构建因果方向。我们使用对数优势计分(LOD score)评估连接两个表型的每条边的因果方向。这种新方法可应用于许多不同的群体结构,包括近交和远交杂交以及自然群体,并且可以适应反馈回路。我们在模拟研究中评估其性能,并表明我们的方法能以较高的准确率恢复网络边并正确推断因果方向。最后,我们用一个涉及来自实验杂交的基因表达和代谢物性状的例子来说明我们的方法。
A major goal in the study of complex traits is to decipher the causal interrelationships among correlated phenotypes. Current methods mostly yield undirected networks that connect. phenotypes without causal orientation. Sonic of these connections may be spurious due to partial correlation that is not causal. We show how to build causal direction into an undirected network of phenotypes by including causal QTL for each phenotype. We evaluate causal direction for each edge connecting two phenotypes, using a LOD score. This new approach can be applied to man), different population structures, including inbred and outbred crosses as well as natural populations, and can accommodate feedback loops. We assess its performance in simulation studies and show that our method recovers network edges and infers causal direction correctly at a high rate. Finally, we illustrate our method with an example involving gene expression and metabolite traits from experimental crosses.