Thrilled to share my lab’s new paper with @ZStorchova in @MolSystBiol on dosage compensation in aneuploid cancers.
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Chromosome copy number changes alter the abundance of hundreds of proteins. However, many of these proteins are "buffered" toward their abundances observed in diploid cells. Despite being widespread, the molecular mechanisms driving dosage compensation remain largely unknown.
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To study this, we established a "Buffering Ratio" to quantify dosage compensation at single-gene resolution. We then trained ML models on pan-cancer datasets, and we achieved high accuracy in predicting which proteins undergo buffering in both cell lines and tumor samples.
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Why does this matter? We found that high buffering levels with a tumor correlate with reduced protein stress. By effectively compensating for gene imbalances, these cells can alleviate the stresses introduced by aneuploidy, potentially providing them with a significant advantage.
Jan 23, 2026 · 4:32 PM UTC
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In contrast, cancers with weak buffering levels are especially sensitive to drugs targeting protein folding and the DNA damage response, potentially revealing a class of vulnerabilities in certain aneuploid cancers.
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Overall, we believe that dosage compensation is a crucial mechanism driving the resilience of aneuploid cancers. Moving forward, we want to determine whether we can interfere with this buffering machinery to selectively undermine protein homeostasis in aneuploid cells.
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Check out the paper here and let me know if you have any questions or feedback! link.springer.com/article/10….
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