Yesterday's issue of Cell contained not one, not two, but four studies in which cell lines (Vero, A549, and two Huh7.5s) were subjected to Crispr-based knockouts in order to determine host factors that enhance amenability to Covid-19 invasion. We've entered the datasets into our database. How do the four studies compare?
B) Identification of Required Host Factors for SARS-CoV-2... (A549)
C) Genetic Screens Identify Host Factors for SARS-CoV-2... (Huh7)
D) Genome-Scale Identification of SARS-CoV-2... (Huh7)
Colors indicate weak anticorrelation (blue), weak correlation (pink), and strong correlation (red).
Actually, only the two Huh7 studies show decent correlation (log(P) = -14). Three of the studies do show Ace2, the well-characterized Covid-19 entry receptor, at the top, or near the top, of the lists. Ace2 narrowly missed our cutoffs in the fourth study (study D). That's comforting.
However, if we're using cell lines to discern host factors that are commonly targeted by Covid-19, am I wrong in thinking these results are a bit underwhelming? Even in the case of the Huh7 studies, an intersection of 21 of 377 total transcripts* generated the aforementioned p-value. Given that the two studies were replicates, shouldn't we expect more extreme significance?
Of course, the two Huh studies weren't exact replicates. Without scanning the papers, different viral MOIs, media, infection periods, etc., were certainly used. Further, I can't say the lack of overlap between these studies is surprising...it happens again and again. But why? Cell does offer a "preview" article that makes mention of differences, but primarily breezes over this issue.
One possible resolution to the question of weak overlaps between studies is this: the virus hasn't evolved to interact with 500 host factors to do its job. It needs a handful. Why should we expect massive overlaps between gene sets from each study if most of the genes in these sets are mere "background?"
We're not finished with our Alzheimer's series...more to come shortly.
*these numbers, of course, depend on our own cutoffs. We won't bore you with a description of our procedure, but there's nothing exotic going on.
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