Beau J, Delaunay F, Lacoche S, Gréchez-Cassiau A, Lévi F
Chronothérapeutique des cancers, Inserm E 0354, hôpital Paul-Brousse, 12, avenue P. Vaillant-Couturier, 94800 Villejuif, France.
Pathol Biol (Paris). 2005 Jun;53(5):295-9. doi: 10.1016/j.patbio.2004.12.011. Epub 2005 Jan 20.
DNA microarrays allow to simultaneously determine the expression level of thousands of genes. A nycthemeral study must enable to conclude which ones show a circadian rhythm. Two aspects prove this to be quite difficult: firstly, what does "circadian" exactly mean and how to quantify this qualification, and secondly which genes pertain to this definition. Our method, derived from linear optimisation procedures, consists in determining a cost function, depending from magnitudes characterising the notion of circadian rhythm. Given number of genes present on the microarray are known to be expressed rhythmically; their time series are considered as reference series. We have further constructed random series having the same temporal structure as the circadian gene series. We then carried out an optimisation procedure to determine the weighting coefficients in order to obtain a cost function value which orders the time series as follows: the reference series are in the first rows and the random series have low scores. We have tested this method on over 6000 genes expressed in mouse liver. We obtained a circadian gene detection probability of 100% with a false positive rate inferior to 1%.
DNA微阵列技术能够同时测定数千个基因的表达水平。一项昼夜节律研究必须能够确定哪些基因呈现出昼夜节律。有两个方面证明这相当困难：首先，“昼夜节律”究竟是什么意思以及如何量化这种特性；其次，哪些基因符合这个定义。我们的方法源自线性优化程序，包括确定一个成本函数，该函数取决于表征昼夜节律概念的量值。已知微阵列上存在的特定数量的基因有节律地表达；它们的时间序列被视为参考序列。我们还构建了与昼夜节律基因序列具有相同时间结构的随机序列。然后我们进行了一个优化程序来确定加权系数，以便获得一个成本函数值，该值对时间序列进行如下排序：参考序列排在前几行，而随机序列得分较低。我们已经在小鼠肝脏中表达的6000多个基因上测试了这种方法。我们获得了100%的昼夜节律基因检测概率，假阳性率低于1%。
