This paper presents a novel approach to prole-prole comparison. The method compares two input proles (like those that are generated by PSI-BLAST) and assigns a similarity score to assess their statistical similarity. Our prole-prole comparison tool, which allows for gaps, can be used to detect weak similarities between protein families. It has also been optimized to produce alignments that are in very good agreement with structural alignments. Tests show that the prole-prole alignments are indeed highly correlated with similarities between secondary structure elements and tertiary structure. Exhaustive evaluations show that our method is signicantly more sensitive in detecting distant homologies than the popular prole-based search programs PSI-BLAST and IMPALA. The relative improvement is the same order of magnitude as the improvement of PSI-BLAST relative to BLAST. Our new tool often detects similarities that fall within the twilight zone of sequence similarity

Sequence similarity searches today are the most effective method for exploiting the information in the rapidly growing DNA and protein sequence databases. One of the most dramatic improvements

Over 3:6 million bases of DNA sequence from chromosome III of the C. elegans have been determined. The availability of this extended region of contiguous sequence has allowed us to analyze the nature and prevalence of repetitive sequences in the genome of a eukaryotic organism with a high gene density. We have assembled a Repeat Pattern Toolkit (RPT) to analyze the patterns of repeats occurring in DNA. The tools include identifying signi øcant local alignments (utilizing both two-way and three-way alignments), dividing the set of alignments into connected components (signifying repeat families), computing evolutionary distance between repeat family members, constructing minimum spanning trees from the connected components, and visualizing the evolution of the repeat families. Over 7000 families of repetitive sequences were identiøed. The size of the families ranged from isolated pairs to over 1600 segments of similar sequence. Approximately 12:3% of the analyzed sequence participates i...

functional sequence elements by multiple

Measuring in a quantitative, statistical sense the degree to which structural and functional information can be ``transferred' ' between pairs of related protein sequences at various levels of similarity is an essential prerequisite for robust genome annotation. To this end, we performed pairwise sequence, structure and function comparisons on 30,000 pairs of protein domains with known structure and function. Our domain pairs, which are constructed according to the SCOP fold classi®cation, range in similarity from just sharing a fold, to being nearly identical. Our results show that traditional scores for sequence and structure similarity have the same basic exponential relationship as observed previously, with structural divergence, measured in RMS, being exponentially related to sequence divergence, measured in percent identity. However, as the scale of our survey is much larger than any previous investigations, our results have greater statistical weight and precision. We have been able to express the relationship of sequence and structure similarity using