Abstract: Described herein are systems, methods, and compositions for the precise editing of DNA sequence(s) at specific loci to alter expression of target gene products at the pre-transcriptional or post-transcriptional level in a durable fashion, termed Stable and Heritable Alteration by Precision Editing (SHAPE). The SHAPE platform utilizes genetic modifiers (e.g., nucleases, (CRISPR guided) transposases, recombinases, base editors, and prime editors) to install specific sequence motifs at target sequences through precision genome engineering.

Abstract: Systems and methods are provided for aligning a first sequence and a second sequence. A gap vector is populated with a plurality of gap penalty values representing a respective plurality of locations along the first sequence, such that a first gap penalty value associated with a first location of the plurality of locations is different than a second gap penalty value associated with a second location of the plurality of locations. For each of a set of possible alignments of the first sequence and the second sequence, a score is generated representing the fitness of each possible alignment. The score for each possible alignment is determined according to at least a match incentive, a mismatch penalty, and the gap vector. Z possible alignment of the set of possible alignments having a best score is selected as an alignment between the first sequence and the second sequence.