Latest posts tagged with #VariantEffects on Bluesky
🧬 New VESS talk alert! "Understanding GPCRs with massive mutagenesis" with Taylor Mighell @crg.eu @sangerinstitute.bsky.social @embo.org @cam.ac.uk
Watch the Dec 2 seminar now on YouTube
#VariantEffects #GPCR #FunctionalGenomics
🎥 www.youtube.com/watch?v=lSFt...
🎥 My Variant Effects Seminar Series (VESS) talk is now on YouTube! I discuss how DropSynth-based gene synthesis reveals how bacterial DHFR variants evolve antibiotic resistance. Thanks to @varianteffect.bsky.social for the invite!
🔗 www.youtube.com/watch?v=KiA9...
#VESS #VariantEffects #DropSynth
A @brotmanbaty.bsky.social-led paper shows that #VariantEffects span a multi-dimensional continuum, rather than a pathogenic-benign binary, or 1-D spectrum.
Learn more about how Drs. Sriram Pendyala and Doug Fowler used VIS-seq to visualize molecular and cellular phenotypes: https://bit.ly/47yrhTI
Delighted for this to be published at AJHG @ajhgnews.bsky.social ! Updates vs the preprint include new comparisons to AlphaMissense and other predictors. We hope this map will help improve clinical variant interpretation in MUTYH! #VUS #VariantEffects #ColorectalCancer www.cell.com/ajhg/fulltex...
Fig. 1: MultiSTEP enables at-scale measurement of variant effects in secreted proteins. a, Secreted proteins make up approximately 10% of the human proteome. b, Cumulative number of missense variants in secreted proteins deposited in ClinVar from 2016 to 2023, colored by clinical interpretation. c, MultiSTEP retains secreted proteins on the cell surface, establishing a physical link between genotype and phenotype (left). Cells expressing a library of variants of the target protein are sorted into bins based upon intensity of fluorescent antibody binding, followed by deep sequencing to derive a functional score for each individual variant (middle). The result is a variant effect map (right). d, MultiSTEP design. Secreted protein-coding sequences (Sec Pro) are cloned into an attB-containing landing pad donor plasmid containing a unique degenerate barcode (BC). Secreted proteins are engineered to have C-terminally fused (GGGGS)2 flexible linkers (L1 and L2) attached to a single-pass transmembrane (TM) domain. In between the linkers is a Strep II epitope tag for surface detection (St). The construct contains an internal ribosomal entry site (IRES), driving co-transcription of an mCherry fluorophore that serves as a transcriptional control. e–g, Flow cytometry of known well-secreted (p.A37T, p.S220T, WT) and poorly secreted (p.C28Y) FIX variants displayed using MultiSTEP (n ~ 30,000 cells per variant). Unrecombined cells do not display FIX and serve as a negative control. Fluorescent signal was generated by staining the library with either an anti-FIX heavy chain antibody (e), an anti-FIX light chain antibody (f) or an anti-Strep II tag antibody (g).
Our paper on building multiplex assays of variant effect for secreted proteins, starting with FIX, is finally (finally!) out on @natsmb.nature.com 🎉
www.nature.com/articles/s41... @varianteffect.bsky.social #hemesky #varianteffects
Today! with Ben Li (University of Michigan Medical School) & Vahid Aslanzadeh (@edinburgh-uni.bsky.social)
ℹ️ www.varianteffect.org/seminar-seri...
#Insulin #FunctionalGenomics #VariantEffects #Seminar
🗓️Coming up on March 4th!
ℹ️ www.varianteffect.org/seminar-series #VariantEffectPredictor #VariantEffects
#FunctionalGenomics #Seminar
What a year! #VariantEffects #Seminar
ℹ️ www.varianteffect.org/previous-sem...
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