The detection of genomic structural variation (SV) has advanced tremendously in recent years due to progress in high-throughput sequencing technologies. Novel sequence insertions, insertions without similarity to a human reference genome, have received less attention than other types of SVs due to the computational challenges in their detection from short read sequencing data, which inherently involves de novo assembly. Dexc2xa0novo assembly is not only computationally challenging, but also requires high-quality data. Although the reads from a single individual may not always meet this requirement, using reads from multiple individuals can increase power to detect novel insertions.