The BLAST programs are widely used tools for searching protein and DNA databases for sequence similarities. For protein comparisons, a variety of definitional, algorithmic and statistical refinements described here permits the execution time of the BLAST programs to be decreased substantially while enhancing their sensitivity to weak similarities. A new criterion for triggering the extension of word hits, combined with a new heuristic for generating gapped alignments, yields a gapped BLAST program that runs at approximately three times the speed of the original. In addition, a method is introduced for automatically combining statistically significant alignments produced by BLAST into a position-specific score matrix, and searching the database using this matrix. The resulting Position-Specific Iterated BLAST (PSIBLAST) program runs at approximately the same speed per iteration as gapped BLAST, but in many cases is much more sensitive to weak but biologically relevant sequence similarities. PSI-BLAST is used to uncover several new and interesting members of the BRCT superfamily.

Computer codes for computation and comparison of RNA secondary structures, the Vienna RNA package, are presented, that are based on dynamic programming algorithms and aim at predictions of structures with minimum free energies as well as at computations of the equilibrium partition functions and base pairing probabilities. An efficient heuristic for the inverse folding problem of RNA is introduced. In addition we present compact and efficient programs for the comparison of RNA secondary structures based on tree editing and alignment. All computer codes are written in ANSI C. They include implementations of modified algorithms on parallel computers with distributed memory. Performance analysis carried out on an Intel Hypercube shows that parallel computing becomes gradually more and more efficient the longer the sequences are.

We survey the current techniques to cope with the problem of string matching allowing errors. This is becoming a more and more relevant issue for many fast growing areas such as information retrieval and computational biology. We focus on online searching and mostly on edit distance, explaining the problem and its relevance, its statistical behavior, its history and current developments, and the central ideas of the algorithms and their complexities. We present a number of experiments to compare the performance of the different algorithms and show which are the best choices according to each case. We conclude with some future work directions and open problems. 1

The problem of searching the elements of a set which are close to a given query element under some similarity criterion has a vast number of applications in many branches of computer science, from pattern recognition to textual and multimedia information retrieval. We are interested in the rather general case where the similarity criterion defines a metric space, instead of the more restricted case of a vector space. A large number of solutions have been proposed in different areas, in many cases without cross-knowledge. Because of this, the same ideas have been reinvented several times, and very different presentations have been given for the same approaches. We

We introduce a new method of constructing kernels on sets whose elements are discrete structures like strings, trees and graphs. The method can be applied iteratively to build a kernel on an infinite set from kernels involving generators of the set. The family of kernels generated generalizes the family of radial basis kernels. It can also be used to define kernels in the form of joint Gibbs probability distributions. Kernels can be built from hidden Markov random elds, generalized regular expressions, pair-HMMs, or ANOVA decompositions. Uses of the method lead to open problems involving the theory of infinitely divisible positive definite functions. Fundamentals of this theory and the theory of reproducing kernel Hilbert spaces are reviewed and applied in establishing the validity of the method.

In this article we show how Optimality Theory yields a highly general Constraint Demotion principle for grammar learning. The resulting learning procedure specifically exploits the grammatical structure of Optimality Theory, independent of the content of substantive constraints defining any given grammatical module. We decompose the learning problem and present formal results for a central subproblem, deducing the constraint ranking particular to a target language, given structural descriptions of positive examples. The structure imposed on the space of possible grammars by Optimality Theory allows efficient convergence to a correct grammar. We discuss implications for learning from overt data only, as well as other learning issues. We argue that Optimality Theory promotes confluence of the demands of more effective learnability and deeper linguistic explanation.

Fast similarity searching in large time-sequence databases has attracted a lot of research interest [1, 5, 2, 6, 3, 10]. All of them use the Euclidean distance (L 2 ), or some variation of L p metrics. L p metrics lead to efficient indexing, thanks to feature extraction (e.g., by keeping the first few DFT coefficients) and subsequent use of fast spatial access methods for the points in feature space. In this work we examine a popular, field-tested dissimilarity function, the "time warping" distance function which permits local accelerations and decelerations in the rate of the signals or sequences. This function is natural and suitable for several applications, like matching of voice, audio and medical signals (e.g., electrocardiograms) However, from the indexing viewpoint it presents two major challenges: (a) it does not lead to any natural "features", precluding the use of spatial access methods (b) it is quadratic (O(len 1 len 2 )) on the length of the sequences involved. Here we ...

The problems of finding a longest common subsequence of two sequences A and B and a shortest edit script for transforming A into B have long been known to be dual problems. In this paper, they are shown to be equivalent to finding a shortest/longest path in an edit graph. Using this perspective, a simple O(ND) time and space algorithm is developed where N is the sum of the lengths of A and B and D is the size of the minimum edit script for A and B. The algorithm performs well when differences are small (sequences are similar) and is consequently fast in typical applications. The algorithm is shown to have O(N +D expected-time performance under a basic stochastic model. A refinement of the algorithm requires only O(N) space, and the use of suffix trees leads to an O(NlgN +D ) time variation.

This paper is a survey of approaches and algorithms used for the automatic discovery of patterns in biosequences. Patterns with the expressive power in the class of regular languages are considered, and a classification of pattern languages in this class is developed, covering those patterns which are the most frequently used in molecular bioinformatics. A formulation is given of the problem of the automatic discovery of such patterns from a set of sequences, and an analysis presented of the ways in which an assessment can be made of the significance and usefulness of the discovered patterns. It is shown that this problem is related to problems studied in the field of machine learning. The largest part of this paper comprises a review of a number of existing methods developed to solve this problem and how these relate to each other, focusing on the algorithms underlying the approaches. A comparison is given of the algorithms, and examples are given of patterns that have been discovered...

The recognition of human gestures and facial expressions in image sequences is an important and challenging problem that enables a host of human-computer interaction applications. This paper describes a framework for incremental recognition of human motion that extends the "Condensation" algorithm proposed by Isard and Blake (ECCV'96). Humnan motions are