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Homology-based taxonomic assignment is impeded by differences between the unassigned read and reference database, forcing a rank-specific classification to the closest (and possibly incorrect) reference lineage. This assignment may be correct only to a general rank (e.g. order) and incorrect below that rank (e.g. family and genus). Algorithms like LCA avoid this by varying the predicted taxonomic rank based on matches to a set of taxonomic references. LCA and related approaches can be conservative, especially if best matches are taxonomically widespread because of events such as lateral gene transfer (LGT).

SPANNER: taxonomic assignment of sequences using pyramid matching of similarity profiles