ON DISTINGUISHING UNIQUE COMBINATIONS IN BIOLOGICAL SEQUENCES

The problem of defining combinations of variants unique to a sequence is efficiently addressed as a set covering computation, The unique-com binations method is introduced, which identifies patterns in biologica l sequence data that distinguish a sequence from a group of other sequ ences, This method is further developed to describe features consisten tly present in one group of sequences but not in a second group, The a pproach is incorporated into a novel analytical tool, designed for use in studies of polymorphic sequence data, such as mitochondrial, human leukocyte antigen (HLA), or viral pathogen sequences, The unique comb inations method is well suited to applications in medical genetics and evolutionary genetics, An example implementation of the unique-combin ations method yields greatly improved risk assessment for insulin-depe ndent diabetes mellitus (IDDM) from amino acid patterns isolated in an analysis of HLA class II DQA1-DQB1 patient and control genotypes.