And lastly, come chat with me about Phoebe Dace's latest work on performing saturation genome editing of BRCA1 across cell types at poster 9004T, Thursday 2:30-4:30pm. Or come by just to say hi!

On Friday, @chloeterwagne.bsky.social will present:

“A scalable framework to link rare human variants to disease phenotypes using pooled prime editing”

Friday Oct 17th at 1:40pm, Rm205ABC

You can also catch up with Chloé at her poster, 5002T, Thursday 2:30-4:30

Tomorrow, October 16 at 2:00 pm,
@magdaarmas.bsky.social presents a new method:

"Modulating gene expression in human cells via high-throughput prime editing of regulatory elements"
[Rm210AB]

This year the lab is also participating in the Crick's Future Leaders in Biomedical Sciences scholarship programme, which has opened for candidates of Black or mixed Black heritage.

www.crick.ac.uk/careers-and-...

Congrats, Mike!

Many thanks!

This story is the PhD work of Phoebe Dace, who has done remarkably well to bring this all together. Congrats, Phoebe! 👏
Thanks to the lab, Nicole, @lcubes.bsky.social @chloeterwagne.bsky.social and Megan), our great collaborators, and @crick.ac.uk & @cancerresearchuk.org for vital funding. 🙏 END/16

Rather than confounding clinical interpretation, having data from multiple models is clearly preferable. A path forward to more precisely calibrating the risk caused by individual variants is to integrate functional evidence from multiple experimental data sets generated at scale. 15/n

In summary, this work reveals the extent to which variant effects can be contingent upon the cell model used. As quality functional data from a single cell line often tips the balance of evidence in favour of pathogenicity or benignity, this is critical to recognise. 14/n

We’ve opted to release all function scores now (see Supplementary Tables). While this data hasn't yet been peer reviewed, we hope sharing now speeds up others' research and allows performance to be assessed across diverse cohorts. Please reach out with questions regarding specific variants. 13/n

Finally, we used gold-standard sets of variants to calibrate the strength of evidence provided by scores from each cell line individually and produced ACMG/AMP-style evidence codes, which we anticipate will improve BRCA1 variant classification. 12/n

Phoebe also took care to test p.R1699Q in both lines, a variant known to confer intermediate breast cancer risk (pubmed.ncbi.nlm.nih.gov/22889855/). Indeed, p.R1699Q scored discordantly between HAP1 and HMEC, as did all 7 other variants tested thought to cause intermediate cancer risk. 11/n