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Old 05-07-2015, 09:56 AM   #8
mbblack
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Location: Research Triangle Park, NC

Join Date: Aug 2009
Posts: 245
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Yes, I've done some comparative studies of multiple tissues from the same animals (eg. rodent liver & lung from inhalation studies) and one can get near completely opposite differential expression of the same genes between tissues. Even many kinases can be up or down regulated under some chemical exposures, and may be differentially affected in different tissues. After 20 odd years of studying gene expression in invertebrates and mammals, I'm not at all surprized any more when any particular gene is highly differentially expressed (even when I admit I cannot make sense of some of them given the apparent biological context of the experimental condition I'm studying).

Expression is highly context dependent and there is a lot of literature on that. Species, sex, life stage, tissue, nutritional state, health state, environmental affects, inter-population differences, etc, etc - all of these things are known to impact measured gene expression. Given that, I'll play devils advocate and ask why you would even expect that there would be such a thing as an invariantly low expression gene in the first place?

And, keep in mind that RNA-seq is not an absolute quantification of expression to begin with. It is a relative estimate of expression and we know that not all available RNAs in a cell are sampled equally in any sequencing experiment (which also in turn then begs the question of how low is considered low expression - what's your cutoff there, and how variable is invariant?). Even were you to control for as many variables as possible, but did a sampling time course every 30-60 minutes for a day (or whatever), how much variation do you think you would see in many of your low count features just by sampling the same pool of cells/tissue across a diurnal cycle (or a feeding cycle, or a menstrual cycle or any other biologically cyclical process)?
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Michael Black, Ph.D.
ScitoVation LLC. RTP, N.C.

Last edited by mbblack; 05-07-2015 at 10:07 AM.
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