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Craig Kaplan
@triggerloop.bsky.social

Can’t wait to dig into this- and very much would like to look at the negative results for synonymous mutants (they rarely have effect in this assay, consistent with baseline expectation)

James Boocock@theboocock.bsky.social

Excited to share our preprint! “Genome-scale base editing reveals the functional effects of variants in yeast” Using high-throughput base editing, we measured the growth effects of 308,461 variants, identifying 18,009 with significant effects. #Genomics #CRISPR 1/8 www.biorxiv.org/content/10.6...

biorxiv.orgGenome-scale base editing reveals the functional effects of variants in yeastGenome sequencing has catalogued vast genetic diversity, but the functional consequences of most variants remain unknown. Here, we used genome-scale CRISPR base editing to measure the growth effects o...

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James Boocock
@theboocock.bsky.social

Thanks! We paid extra attention to this particular question in the manuscript. We compared both the rate and the median effect size for both classes, and added additional statistical controls for potential base editing effects. Everything we did supports the differece between these variant types.

Craig Kaplan
@triggerloop.bsky.social

Thank you- prob should cite their followup as well academic.oup.com/mbe/article/... even though I think their experiment is still flawed. Potentially it could be useful to do statistics on what the smallest fitness effect is that you think you can distinguish in the assay 1/

academic.oup.comFurther Evidence for Strong Nonneutrality of Yeast Synonymous MutationsAbstract. Although synonymous mutations are commonly assumed neutral or nearly so, recent years have seen reports of fitness effects of synonymous mutation
Craig Kaplan
@triggerloop.bsky.social

But having clear difference between synonymous and non synonymous already argues against their conclusion (they say they were the same). But the key idea really is that there are many of both that have no effect not that any mutation has a tiny effect