We often speak of our trove of gene expression data: RNA measurements from different human tissues, which allow us to identify genes that are expressed abnormally in disease patients compared to healthy people. By the time it gets to us, that RNA has been converted first into cDNA, then into a microarray or RNA-seq readout, then into a publication, and finally into an entry in a neat public database. But like babies and sausage, we must eventually pause to consider where this RNA comes from. The answer, especially for brain diseases, is often cadavers (otherwise known as dead people).
Realizing that so much scientific knowledge comes from the dearly departed initially gave me the heebie jeebies. I knew there were no other options, as brain biopsies are incredibly unpopular among the living. But weren’t readouts from dead tissues vastly different from live ones? My naïve intuition was that biological readouts would be like the electronic displays that report system diagnostics on my motorcycle: once the machine’s been turned off, the measurements become significantly less accurate reflections of the bike’s functioning state.
However, apparently one cannot extrapolate this logic from hogs to humans. It turns out that RNA, particularly in brain tissue, is quite stable post-mortem, and a reliable snapshot of brain function in life. Post-mortem protein measurements can be very robust as well; a recent study of more than 3,600 human cadaver brains has shifted the paradigm on which protein is the primary driver of Alzheimer’s Disease.
In a way, twoXAR’s work corroborates this principle. Our gene expression-based models of Parkinson’s Disease, schizophrenia, and Alzheimer’s Disease yield excellent predictions of known treatments and exciting, sensible repurposing candidates. Thus, I have come to acknowledge that like zombies, “undead data” can be surprisingly powerful.