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Split-alignments provide base-pair-resolution evidence of genomic rearrangements. In practice, they are found by first computing high-scoring local alignments, parts of which are then combined into a split-alignment. This approach is challenging when aligning a short read to a large and repetitive reference, as it tends to produce many spurious local alignments leading to ambiguities in identifying the correct split-alignment. This problem is further exacerbated by the fact that rearrangements tend to occur in repeat-rich regions.

Combining probabilistic alignments with read pair information improves accuracy of split-alignments