The normexp likelihood is difficult to compute with full numerical accuracy. In limma version 2.3.1, I made what I thought was a slight improvement in the likelihood calculation, which has instead had the effect of causing the normexp algorithm to sometimes (more often than before) converge to extreme parameter values, producing the effect that you see. I believe the problem is fixed in limma 2.4.5 and later. Try upgrading and see. Best wishes Gordon >Date: Thu, 26 Jan 2006 16:46:04 +0100 >From: Georg Otto <georg.otto at="" tuebingen.mpg.de=""> >Subject: [BioC] limma backgroundCorrect problem >To: bioconductor at stat.math.ethz.ch > >Hi, > >I am using limma for background correction and normalization of >two-color arrays. I have encountered a problem that I do not quite >understand: Using > > > RGb<-backgroundCorrect(RG, method="normexp", offset=50) > >I get the warning message: > >NaNs produced in: pnorm(q, mean, sd, lower.tail, log.p) > > >However > > > which(is.nan(RGb$R) == TRUE) > > which(is.nan(RGb$R) == TRUE) > >does not indicate NANs in the result. The numbers pruduced look >strange as well: > > > RGb$G[1:5,] > array1 array2 >[1,] 2.481014e+79 2.361013e+74 >[2,] 2.481014e+79 2.361013e+74 >[3,] 2.481014e+79 2.361013e+74 >[4,] 2.481014e+79 2.361013e+74 >[5,] 2.481014e+79 2.361013e+74 > array3 array4 >[1,] 2099.87545 1.577257e+79 >[2,] 53.75734 1.577257e+79 >[3,] 118.30759 1.577257e+79 >[4,] 63.07401 1.577257e+79 >[5,] 339.25502 1.577257e+79 > array5 array6 >[1,] 1.153553e+85 1644.20247 >[2,] 1.153553e+85 51.08563 >[3,] 1.153553e+85 138.33239 >[4,] 1.153553e+85 62.48045 >[5,] 1.153553e+85 612.04439 > > >My original foreground and background data however look decent (I >think) > > > > RG$G[1:5,] > array1 array2 >[1,] 1827.41975 1744.73457 >[2,] 55.50345 55.98621 >[3,] 110.92857 128.59155 >[4,] 60.77931 62.81119 >[5,] 81.86429 128.24161 > array3 array4 >[1,] 2102.72500 1573.95541 >[2,] 55.60690 53.40936 >[3,] 120.15714 96.55072 >[4,] 66.92357 60.33103 >[5,] 341.10458 262.14966 > array5 array6 >[1,] 2279.76687 1645.17073 >[2,] 54.75172 52.96226 >[3,] 130.19728 139.30065 >[4,] 70.24615 64.44872 >[5,] 709.73718 614.01266 > > > > RG$Gb[1:5,] > array1 array2 >[1,] 44 45 >[2,] 44 44 >[3,] 44 45 >[4,] 45 45 >[5,] 44 45 > array3 array4 >[1,] 48 46 >[2,] 47 47 >[3,] 47 46 >[4,] 49 46 >[5,] 47 46 > array5 array6 >[1,] 47 46 >[2,] 47 47 >[3,] 46 46 >[4,] 47 47 >[5,] 46 47 > > >Other subtraction methods (eg. "subtract") work well. > >I am running limma 2.4.4 on R 2.2.1 > >Any idea what is going wrong here? > >Best, > >Georg