A block is an ungapped local multiple alignment of amino acid sequences from a group of related proteins. Ideally, the contiguous stretch of residues represented by a block is conserved for biological function. Blocks have depth (the number of sequences) and width (the number of aligned positions). There are currently several useful programs for finding blocks in a group of related sequences that I do not discuss in detail here. Among these, Motif (Smith et al., 1990) and Asset (Neuwald and Green, 1994) both align blocks on occurrences of certain types of patterns found in the sequences; Gibbs (Lawrence et al., 1993; Neuwald et al., 1995) and MEME (Bailey and Elkan, 1994) both look for statistically optimal local alignments; and Macaw (Schuler et al., 1991) and Somap (Parry-Smith and Attwood, 1992) both give the user assistance in finding blocks interactively. After candidate blocks are identified by a block-finding method, they can be evaluated and assembled into a set representing the protein group, resulting in a multiple alignment consisting of ungapped regions separated by unaligned regions of variable length. The block assembly process is the subject of this chapter. Both the Blocks (Henikoff and Henikoff, 1996a) and Prints (Attwood and Beck, 1994) databases consist of such sets of blocks and between them currently represent 1,163 different protein groups. These collections of blocks are more sensitive and efficient for classifying new sequences into known protein groups than are collections of individual sequences, as demonstrated by comprehensive evaluations (Henikoff and Henikoff, 1994b, 1997), by genomic studies (Green et al., 1993), and by individual studies (Posfai et al., 1988; Henikoff, 1992, 1993; Attwood and Findlay, 1993; Pietrokovski, 1994; Brown, 1995). Issues that must be addressed during block assembly include the number of blocks provided to the assembly module by the block finders, block width, the number of times a block occurs in each sequence (zero to many), overlap of blocks, and the order of multiple blocks within each sequence. Once these issues are decided, it is necessary to score individual competing blocks and then competing sets of blocks.
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