Jimmie Ye
@yimmieg.bsky.social
Genome scientist becoming engineer. Immunologist. Geneticist. Dabbles in statistics and statistical learning. Home @UCSF, affiliated with Arc and PICI.
8/n: Lymphoma Connections:
* P2RY8 is mutated frequently in GC-derived B cell lymphomas.
* Almost all such tumor variants reduce P2RY8 function, suggesting that escaping confinement leads to uncontrolled growth.
* Potential path toward novel therapeutic strategies targeting P2RY8 & related pathways.
* P2RY8 is mutated frequently in GC-derived B cell lymphomas.
* Almost all such tumor variants reduce P2RY8 function, suggesting that escaping confinement leads to uncontrolled growth.
* Potential path toward novel therapeutic strategies targeting P2RY8 & related pathways.
March 7, 2025 at 6:50 PM
8/n: Lymphoma Connections:
* P2RY8 is mutated frequently in GC-derived B cell lymphomas.
* Almost all such tumor variants reduce P2RY8 function, suggesting that escaping confinement leads to uncontrolled growth.
* Potential path toward novel therapeutic strategies targeting P2RY8 & related pathways.
* P2RY8 is mutated frequently in GC-derived B cell lymphomas.
* Almost all such tumor variants reduce P2RY8 function, suggesting that escaping confinement leads to uncontrolled growth.
* Potential path toward novel therapeutic strategies targeting P2RY8 & related pathways.
7/n: Computational Twist:
* We compared DMS results with zero shot variant effect predictions using protein language models (PLMs).
* Found decent correlation (~Spearman 0.6)—but much better after “fine-tuning” (~Spearman 0.8) with ~20% of real experimental data points. Thanks Vasilis Ntranos!
* We compared DMS results with zero shot variant effect predictions using protein language models (PLMs).
* Found decent correlation (~Spearman 0.6)—but much better after “fine-tuning” (~Spearman 0.8) with ~20% of real experimental data points. Thanks Vasilis Ntranos!
March 7, 2025 at 6:50 PM
7/n: Computational Twist:
* We compared DMS results with zero shot variant effect predictions using protein language models (PLMs).
* Found decent correlation (~Spearman 0.6)—but much better after “fine-tuning” (~Spearman 0.8) with ~20% of real experimental data points. Thanks Vasilis Ntranos!
* We compared DMS results with zero shot variant effect predictions using protein language models (PLMs).
* Found decent correlation (~Spearman 0.6)—but much better after “fine-tuning” (~Spearman 0.8) with ~20% of real experimental data points. Thanks Vasilis Ntranos!
5/n: Christian Billesboelle from the Manglik lab solved the structure by Cryo-EM:
* Captured P2RY8 in its active conformation bound to its ligand.
* Showed key contacts needed for ligand binding vs. G-protein interaction.
* Helped interpret which amino acids are especially critical for function.
* Captured P2RY8 in its active conformation bound to its ligand.
* Showed key contacts needed for ligand binding vs. G-protein interaction.
* Helped interpret which amino acids are especially critical for function.
March 7, 2025 at 6:50 PM
5/n: Christian Billesboelle from the Manglik lab solved the structure by Cryo-EM:
* Captured P2RY8 in its active conformation bound to its ligand.
* Showed key contacts needed for ligand binding vs. G-protein interaction.
* Helped interpret which amino acids are especially critical for function.
* Captured P2RY8 in its active conformation bound to its ligand.
* Showed key contacts needed for ligand binding vs. G-protein interaction.
* Helped interpret which amino acids are especially critical for function.
3/n: Taylor introduced nearly every possible missense substitution (7,045 variants) into B cells lacking endogenous P2RY8. Effects on 3 phenotypes were measured: expression, migration, & proliferation. We observed an inverse relationship between expression & migration across the allelic series.
March 7, 2025 at 6:50 PM
3/n: Taylor introduced nearly every possible missense substitution (7,045 variants) into B cells lacking endogenous P2RY8. Effects on 3 phenotypes were measured: expression, migration, & proliferation. We observed an inverse relationship between expression & migration across the allelic series.