In metagenomic read classification, spaced seeds (k-mers with wildcard positions) beat traditional contiguous k-mers — but with an explicit operating envelope: the advantage holds below ~0.9 sequence identity; for very high-quality alignments (identity ~0.95+) contiguous k-mers with hit-number scoring win. Jaccard-index scoring amplifies the spaced-seed advantage for small-weight seeds.

— In our words · Source: Spaced seeds improve k-mer-based metagenomic classification (Karel Brinda)