These bubbles must be “clean”, or simply a divergence from the reference genome, but cannot be caused by deletions of DNA bases. This algorithm can have high false positive rates since there is a difficulty of separating repeat- and variant-induced bubbles; however, there is often a reference genome to help improve reliability. The reference genome also helps in the detection of variants and is essential to detect variant sites.[1] Recently, scientists have discovered a way to use the bubble calling algorithm with copy number variation detection to allow for an opportunity of unbiased detection of these variations in the future[5]