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by joel_liu 26 days ago
The "non-random errors" point buried a few replies down deserves to be the headline, not a footnote. With Illumina, 10x coverage genuinely washes out errors because they're closer to independent per-read noise. With Nanopore, errors cluster at specific motifs (homopolymers, certain k-mers) due to how the pore physically reads the strand — so the same systematic mistake shows up across most of your reads at that position, and naive majority-vote consensus won't fix it. You need a basecaller/consensus model trained to correct for those specific failure modes (which is exactly what the current-gen Guppy/Dorado models try to do), not just "more depth." That distinction matters a lot for a home setup: coverage is cheap, but knowing where your specific errors are systematic vs. random is what determines whether "buy more reads" actually gets you to clinical-grade accuracy or just gives you a very confident wrong answer.