How do stagger sequences or heterogeneity spacers introduce diversity?

Stagger sequences or heterogeneity spacers are a series of nucleotides with varying lengths that introduce nucleotide diversity to sequencing reads. When stagger sequences are inserted before a low diversity region, the reads are offset by the stagger sequences, resulting in greater nucleotide diversity.

Illustration of a low diversity region with no stagger sequences:

Illustration of the same region with stagger sequences:

Introducing staggering can help to improve library base diversity, though depending on library design, the resulting library may still be low in base diversity and require phiX spike in to increase base diversity for optimal sequencing performance.

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