Abstract: The present invention relates to a set of oligonucleotides comprising index sequences and wherein the set comprises a plurality of subsets of oligonucleotides with different index sequences, wherein the index sequences of a subset of oligonucleotides differ at least by a non-zero number of sequence changes from each other; and wherein the set comprises at least 2 hierarchical tiers of subsets, wherein index sequences of a higher tier subset are members of a lower tier subset, and wherein the index sequences of a lower tier subset differ by a lower minimum number of sequence changes from each other than the index sequences of a higher tier subset; and wherein the oligonucleotides are assigned to one or more subsets. The invention further relates to methods of generating and using such sets.