Thank the @johndoench.bsky.social and Root labs for depositing these deliciously named libraries, and check out our blog post for more:

Congratulations Ben!

with a great team of collaborators @traver.bsky.social @guilbourque.bsky.social

4️⃣ Why are we excited about this is because this expands our understanding of how chromosome arm deletions are buffered in triple negative breast cancer which should enable us to develop targeted therapies.

3️⃣ Functional assays revealed that chr4p loss is associated with disrupted mitochondrial respiratory function and reduced glycolytic capacity, suggesting metabolic rewiring. Increased reactive oxygen species and lipid peroxidation compromised antioxidant defense mechanisms.

2️⃣ We analyzed DepMap pooled genome-wide CRISPRCas9 screens and identified complex genetic interactions specific to chr4p deletion in basal breast cancer cell models.

1️⃣ We used differential gene expression analysis of patient derived xenografts and cancer cell models to show that chr4p loss is associated with changes in cellular energetics.

Thank you for highlight GSA!

8️⃣ Why are we excited about this is because this is the first systematic investigation of relocalization changes of paralogs and provides insight into their retention in evolution

7️⃣ Finally, our findings are consistent with non-canonical protein isoform abundance as a mechanism for paralog compensation

6️⃣ Redistributed proteins were encoded by functionally redundant paralogs and showed genetic and protein interactions in the subcellular compartments of their paralogs

6️⃣ Redistributed proteins were encoded by functionally redundant paralogs and showed genetic and protein interactions in the subcellular compartments of their paralogs

5️⃣ Redistribution also captured subcellular localization changes, reciprocal changes were rare consistent with asymmetric divergence of paralogs and cases of dependency were more common than compensation