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Publications of the Week

Differential Coexpression in Human Tissues and the Confounding Effect of Mean Expression Levels

By July 27, 2018No Comments

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 This week we profile a recent publication in Bioinformatics from the laboratory of
 Dr. Paul Pavlidis (pictured)
at the Michael Smith Laboratories.

Can you provide a brief overview of your lab’s current research focus?

My lab does computational biology and bioinformatics research. We’re primarily interested in studying the nervous system, using genomics and genetics data to help understand human conditions like schizophrenia and autism. But we’re also interested in more general questions about how to leverage available genomics data for biological discovery. The paper we just published is from the latter side of the lab, where we’re interested in inferring information about gene networks.

What is the significance of the findings in this publication?

In the analysis of gene expression (transcriptomics), a very popular approach is to look at relationships among genes, so-called co-expression. The idea is genes might be co-expressed for reasons related to their function, and in particular how they are regulated. A closely related idea is that genes which are co-expressed in one condition might not be in another (such as a disease) and that might reflect “re-wiring” of gene regulatory networks. It would be very cool if that worked, but previously reported examples of this kind of “differential co-expression” haven’t been very convincing.

The main thing that seemed to be going on is that genes are simply being up- or down-regulated overall, which is a much simpler and obvious kind of “re-wiring” and not what previous efforts have been claiming to have found. Put simply, if a gene isn’t expressed then it can’t be co-expressed. In the current paper we decided to see if we could find differential co-expression that wasn’t “polluted” with a general change in expression levels – in a sense we did a control experiment. While we did find some of what we called “pure” differential co-expression, it’s a small minority. The conclusion of our paper is that the idea of detecting regulatory re-wiring this way requires a rethink from the field.

What are the next steps for this research?

We tried pretty hard to figure what, if anything, the pure differential co-expression means biologically, but we didn’t turn up anything we felt was compelling. But we have some other ideas that we’re pursuing right now. It could turn out that there is some actual regulatory re-wiring that can be detected this way, but other explanations seem more likely so far.

This research was funded by:

The research in the paper was supported by grants from the US NIH and NSERC.

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