Hi, I am a complete beginner to Linear Models and using the LIMMA package. First I have a general question as to what are good intro texts explaining Linear Models in general. I also have the following specific question. I have 4 samples: wild type (WT), a sample were I turn on a pathway (ON) and two where I knock down the same pathway in two different ways (KO1, KO2). I want to find genes that are significantly changed with the following property: sign(log(ON/WT)) == -sign(log(KO1/WT)) and -sign(log(KO2/WT)) would the following design and contrast matrix be correct type = is a factor with levels WT, ON, KO1, KO2 design = model.matrix(~0 + type) cm = makeContrasts(eff = (ON - WT) - (KO1 - WT) - (KO2 - WT), levels=design) Any help or guidence would be greatly appreciated. Also pointers to suitable documentation explain such matters would be great. Thanks in advance