Carina Biar #ASHG22: ML + genome editing to resolve variants of uncertain significance (VUS) in TSC2 gene.
Starts with the mTOR pathway and a reminder that we have a skyrocketing number of VUSes as we continue to do genomic testing.
Starts with the mTOR pathway and a reminder that we have a skyrocketing number of VUSes as we continue to do genomic testing.
Carina Biar #ASHG22: Wants to use machine learning to predict pathogenicity. Train on a per-gene basis and used ~40 features.
Gene-model does better (86%) than CADD (65%) when testing on known P/LP variants. Benign variants not as easily classified.
Gene-model does better (86%) than CADD (65%) when testing on known P/LP variants. Benign variants not as easily classified.
Carina Biar #ASHG22: CRISPR to knock variants of interest in TSC2 into haploid cell lines. FACS sort + sequence to look for mTOR activity (functional assay here since part of the same pathway).
[ Previous work is here: pubmed.ncbi.nlm.nih.gov/35773235/ ]
[ Previous work is here: pubmed.ncbi.nlm.nih.gov/35773235/ ]
Carina Biar #ASHG22: Now doing prime editing in lab -- have some preliminary data that correlates functional assay to pathogenicity score.
Hope to apply to other mTOR genes.
Hope to apply to other mTOR genes.
As a note: Carina is an undergrad and I'd like to give a shout out to this excellent work + great talk. Very well done!! #ASHG22 #ASHGtrainee
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