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Importantly, we see that attenuated selection on CNAs and SNVs is generic to tumor evolution. This pattern persists across broad and specific tumor sub-type categories. (7/10)pic.twitter.com/bKJ8vSbQUV
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We see the same trend in somatic CNAs. Using a dN/dS-style statistic called dE/dI (fractional overlap of CNAs in [E]xonic versus [I]ntergenic/[I]ntronic regions) – we similarly see that selection on CNAs attenuates as the mutational burden increases. (6/10)pic.twitter.com/LUg6hlRJFk
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To test this idea, we calculated dN/dS in tumors stratified by their mutational burden and observe that negative and positive selection attenuates as more mutations accumulate in tumors. (5/10)pic.twitter.com/WF1WIJ02mV
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Since linkage effects get stronger as mutation rates increase, tumors with elevated mutational burdens should be particularly inefficient at removing deleterious passengers due to genetic hitchhiking and Muller’s Ratchet. (4/10)pic.twitter.com/vVW4z6C6q1
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