A Read-mapping confidence versus repeat-copy similarity. As the similarity between two copies of a repeat increases, the confidence in any read placement within the repeat decreases. At the top of the figure, we show three different tandem repeats with two copies each. Directly beneath these tandem repeats are reads that are sequenced from these regions. For each tandem repeat, we have highlighted and zoomed in on a single read. Starting with the leftmost read (red) from tandem repeat X, we have low confidence when mapping this read within the tandem repeat, because it aligns equally well to both X1 and X2. In the middle example (tandem repeat Y, green), we have a higher confidence in the mapping owing to a single nucleotide difference, making the alignment to Y1 slightly better than Y2. In the rightmost example, the blue read that is sequenced from tandem repeat Z aligns perfectly to Z1, whereas its alignment to Z2 contains three mismatches, giving us a high confidence when mapping the read to Z1. B | Ambiguity in read mapping. The 13 bp read shown along the bottom maps to two locations, a and b, where there is a mismatch at location a and a deletion at b. If mismatches are considered to be less costly, then the alignment program will put the read in location a. However, the source DNA might have a true deletion in location b, meaning that the true position of the read is b.