= Solution
Pooling can erase <between-replicate variation>. One unusually well-covered or highly modified sample can dominate the pooled estimate, hiding an inconsistent biological response. If individual reads are then treated as independent <biological replicates>, uncertainty can be understated through <pseudoreplication>.
A better analysis retains replicate identity and models sample-to-sample variation, while allowing information to be shared about suitable common component parameters. Pooled performance on a larger dataset can be useful, but should not substitute for evidence that the result reproduces across independent biological samples.
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