Overview of the indelMINER algorithm. Panel titled “Identification of candidate reads” shows three of the cases when a read is identified for realignment or paired-end analysis. (a) shows a case when mates align with the expected orientation but one of the mates is only partially aligned, (b) shows a case when one mate from a fragment aligns to a location mpos on the reference, while the other mate does not align, and (c) shows the case when both mates align with the expected relative orientation, but the outer distance constraint is violated. Panel titled “Identification of diagonal” shows the various alignments of the unaligned mate using k-mer comparisons, and the subsequent selection of one of the diagonals based on alignment score and distance from mpos. Panel “Split read alignment” shows the extension of the chosen diagonal, and the panel “Identification of indel” shows the alignment and extension of the remaining sequence from the unaligned mate, to a region around mpos selected based on a user-specified threshold.