Probabilities of spurious connections in gene networks: application to expression time series

Probabilities of spurious connections in gene networks: application to expression time series
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DOI:
10.1093/bioinformatics/bti140
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发表时间:
2005-04-01
期刊:
影响因子:
5.8
通讯作者:
Bickel, DR
Bickel, DR
中科院分区:
生物学3区
文献类型:
--
作者:
Bickel, DR

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动机:随着方法的改进和更多数据的出现,从基因表达微阵列重建基因网络越来越受欢迎。这种网络的可靠性可以通过基因之间的连接是虚假的概率来判断,这种连接是由机会波动而不是真正的生物学关系引起的。结果:与错误发现率和正错误发现率不同,决定性错误发现率(dFDR)完全等于条件概率,而不假设假设真值的独立性或随机性。该特性不仅可用于检测差异基因表达的常见应用,还可用于确定重建基因网络中虚假连接的概率。 dFDR 的估计者可以估计三个概率中的每一个:(1)似乎彼此相关的两个基因缺乏这种关联的概率。 (2) 观察到的两个相关基因的时间顺序有误导性的可能性。 (3) 观察到的两个基因的时间顺序有误导性的可能性,要么因为它们不相关,要么因为它们在没有时间滞后的情况下相关。第一个概率适用于静态和动态基因网络,另外两个概率仅适用于动态基因网络。
Motivation: The reconstruction of gene networks from gene-expression microarrays is gaining popularity as methods improve and as more data become available. The reliability of such networks could be judged by the probability that a connection between genes is spurious, resulting from chance fluctuations rather than from a true biological relationship.Results: Unlike the false discovery rate and positive false discovery rate, the decisive false discovery rate (dFDR) is exactly equal to a conditional probability without assuming independence or the randomness of hypothesis truth values. This property is useful not only in the common application to the detection of differential gene expression, but also in determining the probability of a spurious connection in a reconstructed gene network. Estimators of the dFDR can estimate each of three probabilities: (1) The probability that two genes that appear to be associated with each other lack such association. (2) The probability that a time ordering observed for two associated genes is misleading. (3) The probability that a time ordering observed for two genes is misleading, either because they are not associated or because they are associated without a lag in time. The first probability applies to both static and dynamic gene networks, and the other two only apply to dynamic gene networks.