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285
Near-optimal hashing algorithms for approximate nearest neighbor in high dimensions
, 2008
"... In this article, we give an overview of efficient algorithms for the approximate and exact nearest neighbor problem. The goal is to preprocess a dataset of objects (e.g., images) so that later, given a new query object, one can quickly return the dataset object that is most similar to the query. The ..."
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Cited by 457 (7 self)
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In this article, we give an overview of efficient algorithms for the approximate and exact nearest neighbor problem. The goal is to preprocess a dataset of objects (e.g., images) so that later, given a new query object, one can quickly return the dataset object that is most similar to the query. The problem is of significant interest in a wide variety of areas.
Probabilistic discovery of time series motifs
, 2003
"... Several important time series data mining problems reduce to the core task of finding approximately repeated subsequences in a longer time series. In an earlier work, we formalized the idea of approximately repeated subsequences by introducing the notion of time series motifs. Two limitations of thi ..."
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Cited by 185 (26 self)
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Several important time series data mining problems reduce to the core task of finding approximately repeated subsequences in a longer time series. In an earlier work, we formalized the idea of approximately repeated subsequences by introducing the notion of time series motifs. Two limitations of this work were the poor scalability of the motif discovery algorithm, and the inability to discover motifs in the presence of noise. Here we address these limitations by introducing a novel algorithm inspired by recent advances in the problem of pattern discovery in biosequences. Our algorithm is probabilistic in nature, but as we show empirically and theoretically, it can find time series motifs with very high probability even in the presence of noise or “don’t care ” symbols. Not only is the algorithm fast, but it is an anytime algorithm, producing likely candidate motifs almost immediately, and gradually improving the quality of results over time.
Additivity in protein–DNA interactions: how good an approximation is it
- Nucleic Acids Res
, 2002
"... Man and Stormo and Bulyk et al. recently presented their results on the study of the DNA binding af®nity of proteins. In both of these studies the main conclusion is that the additivity assumption, usually applied in methods to search for binding sites, is not true. In the ®rst study, the analysis o ..."
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Cited by 162 (24 self)
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Man and Stormo and Bulyk et al. recently presented their results on the study of the DNA binding af®nity of proteins. In both of these studies the main conclusion is that the additivity assumption, usually applied in methods to search for binding sites, is not true. In the ®rst study, the analysis of binding af®nity data from the Mnt repressor protein bound to all possible DNA (sub)targets at positions 16 and 17 of the binding site, showed that those positions are not independent. In the second study, the authors analysed DNA binding af®nity data of the wild-type mouse EGR1 protein and four variants differing on the middle ®nger. The binding af®nity of these proteins was measured to all 64 possible trinucleotide (sub)targets of the middle ®nger using microarray technology. The analysis of the measurements also showed interdependence among the positions in the DNA target. In the present report, we review the data of both studies and we reanalyse them using various statistical methods, including a comparison with a multiple regression approach. We conclude that despite the fact that the additivity assumption does not ®t the data perfectly, in most cases it provides a very good approximation of the true nature of the speci®c protein±DNA interactions. Therefore, additive models can be very useful for the discovery and prediction of binding sites in genomic DNA.
Comining phylogenetic data with co-regulated genes to identify regulatory motif
- BIOINFORMATICS
, 2003
"... Motivation: Discovery of regulatory motifs in unaligned DNA sequences remains a fundamental problem in computational biology. Two categories of algorithms have been developed to identify common motifs from a set of DNA sequences. The first can be called a ‘multiple genes, single species’approach. It ..."
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Cited by 136 (11 self)
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Motivation: Discovery of regulatory motifs in unaligned DNA sequences remains a fundamental problem in computational biology. Two categories of algorithms have been developed to identify common motifs from a set of DNA sequences. The first can be called a ‘multiple genes, single species’approach. It proposes that a degenerate motif is embedded in some or all of the otherwise unrelated input sequences and tries to describe a consensus motif and identify its occurrences. It is often used for co-regulated genes identified through experimental approaches. The second approach can be called ‘single gene, multiple species’. It requires orthologous input sequences and tries to identify unusually well conserved regions by phylogen-etic footprinting. Both approaches perform well, but each has some limitations. It is tempting to combine the knowledge of co-regulation among different genes and conservation among orthologous genes to improve our ability to identify motifs. Results: Based on the Consensus algorithm previously established by our group, we introduce a new algorithm called PhyloCon (Phylogenetic Consensus) that takes into account both conservation among orthologous genes and co-regulation of genes within a species. This algorithm first aligns conserved regions of orthologous sequences into multiple sequence alignments, or profiles, then compares profiles representing non-orthologous sequences. Motifs emerge as common regions in these profiles. Here we present a novel statistic to compare profiles of DNA sequences and a greedy approach to search for common subprofiles. We demonstrate that PhyloCon performs well on both synthetic and biological data. Availability: Software available upon request from the authors.
Modeling Dependencies in Protein-DNA Binding Sites
, 2003
"... The availability of whole genome sequences and high-throughput genomic assays opens the door for in silico analysis of transcription regulation. This includes methods for discovering and characterizing the binding sites of DNA-binding proteins, such as transcription factors. A common representation ..."
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Cited by 117 (2 self)
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The availability of whole genome sequences and high-throughput genomic assays opens the door for in silico analysis of transcription regulation. This includes methods for discovering and characterizing the binding sites of DNA-binding proteins, such as transcription factors. A common representation of transcription factor binding sites is aposition specific score matrix (PSSM). This representation makes the strong assumption that binding site positions are independent of each other. In this work, we explore Bayesian network representations of binding sites that provide different tradeoffs between complexity (number of parameters) and the richness of dependencies between positions. We develop the formal machinery for learning such models from data and for estimating the statistical significance of putative binding sites. We then evaluate the ramifications of these richer representations in characterizing binding site motifs and predicting their genomic locations. We show that these richer representations improve over the PSSM model in both tasks.
Finding Motifs in Time Series
, 2002
"... The problem of efficiently locating previously known patterns in a time series database (i.e., query by content) has received much attention and may now largely be regarded as a solved problem. However, from a knowledge discovery viewpoint, a more interesting problem is the enumeration of previously ..."
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Cited by 111 (20 self)
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The problem of efficiently locating previously known patterns in a time series database (i.e., query by content) has received much attention and may now largely be regarded as a solved problem. However, from a knowledge discovery viewpoint, a more interesting problem is the enumeration of previously unknown, frequently occurring patterns. We call such patterns "motifs," because of their close analogy to their discrete counterparts in computation biology. An efficient motif discovery algorithm for time series would be useful as a tool for summarizing and visualizing massive time series databases. In addition, it could be used as a subroutine in various other data mining tasks, including the discovery of association rules, clustering and classification. In this work we carefully motivate, then introduce, a non-trivial definition of time series motifs. We propose an efficient algorithm to discover them, and we demonstrate the utility and efficiency of our approach on several real world datasets.
Finding composite regulatory patterns in DNA sequences
- Bioinformatics
, 2002
"... Pattern discovery in unaligned DNA sequences is a fundamental problem in computational biology with important applications in finding regulatory signals. Current approaches to pattern discovery focus on monad patterns that correspond to relatively short contiguous strings. However, many of the actua ..."
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Cited by 108 (4 self)
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Pattern discovery in unaligned DNA sequences is a fundamental problem in computational biology with important applications in finding regulatory signals. Current approaches to pattern discovery focus on monad patterns that correspond to relatively short contiguous strings. However, many of the actual regulatory signals are composite patterns that are groups of monad patterns that occur near each other. A difficulty in discovering composite patterns is that one or both of the component monad patterns in the group may be “too weak”. Since the traditional monad-based motif finding algorithms usually output one (or a few) high scoring patterns, they often fail to find composite regulatory signals consisting of weak monad parts. In this paper, we present a MITRA (MIsmatch TRee Algorithm) approach for discovering composite signals. We demonstrate that MITRA performs well for both monad and composite patterns by presenting experiments over biological and synthetic data. Availability: MITRA is available at
Nearest Neighbors In High-Dimensional Spaces
, 2004
"... In this chapter we consider the following problem: given a set P of points in a high-dimensional space, construct a data structure which given any query point q nds the point in P closest to q. This problem, called nearest neighbor search is of significant importance to several areas of computer sci ..."
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Cited by 93 (2 self)
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In this chapter we consider the following problem: given a set P of points in a high-dimensional space, construct a data structure which given any query point q nds the point in P closest to q. This problem, called nearest neighbor search is of significant importance to several areas of computer science, including pattern recognition, searching in multimedial data, vector compression [GG91], computational statistics [DW82], and data mining. Many of these applications involve data sets which are very large (e.g., a database containing Web documents could contain over one billion documents). Moreover, the dimensionality of the points is usually large as well (e.g., in the order of a few hundred). Therefore, it is crucial to design algorithms which scale well with the database size as well as with the dimension. The nearest-neighbor problem is an example of a large class of proximity problems, which, roughly speaking, are problems whose definitions involve the notion of...
Efficient Large-Scale Sequence Comparison by Locality-Sensitive Hashing
- Bioinformatics
, 2001
"... Motivation: Comparison of multimegabase genomic DNA sequences is a popular technique for finding and annotating conserved genome features. Performing such comparisons entails finding many short local alignments between sequences up to tens of megabases in length. To process such long sequences e#cie ..."
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Cited by 91 (6 self)
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Motivation: Comparison of multimegabase genomic DNA sequences is a popular technique for finding and annotating conserved genome features. Performing such comparisons entails finding many short local alignments between sequences up to tens of megabases in length. To process such long sequences e#ciently, existing algorithms find alignments by expanding around short runs of matching bases with no substitutions or other di#erences. Unfortunately, exact matches that are short enough to occur often in significant alignments also occur frequently by chance in the background sequence. Thus, these algorithms must trade o# between e#ciency and sensitivity to features without long exact matches. Results: We introduce a new algorithm, lsh-all-pairs, to find ungapped local alignments in genomic sequence with up to a specified fraction of substitutions. The length and substitution rate of these alignments can be chosen so that they appear frequently in significant similarities yet still remain rare in the background sequence. The algorithm finds ungapped alignments e#ciently using a randomized search technique, locality-sensitive hashing. We have found lsh-all-pairs to be both e#cient and sensitive for finding local similarities with as little as 63% identity in mammalian genomic sequences up to tens of megabases in length. Availability: Contact the author at the address below. Contact: jbuhler@cs.washington.edu Supplementary Information: the sequences and local alignment data described in this work are available at http://bio.cs.washington.edu/jbuhler-bioinformatics-2001/. Keywords: local alignment, genome annotation, locality-sensitive hashing Sequence Comparison by Locality-Sensitive Hashing 1
Limitations and potentials of current motif discovery algorithms.
- Nucleic Acids Res
, 2005
"... ABSTRACT Computational methods for de novo identification of gene regulation elements, such as transcription factor binding sites, have proved to be useful for deciphering genetic regulatory networks. However, despite the availability of a large number of algorithms, their strengths and weaknesses ..."
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Cited by 88 (0 self)
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ABSTRACT Computational methods for de novo identification of gene regulation elements, such as transcription factor binding sites, have proved to be useful for deciphering genetic regulatory networks. However, despite the availability of a large number of algorithms, their strengths and weaknesses are not sufficiently understood. Here, we designed a comprehensive set of performance measures and benchmarked five modern sequence-based motif discovery algorithms using large datasets generated from Escherichia coli RegulonDB. Factors that affect the prediction accuracy, scalability and reliability are characterized. It is revealed that the nucleotide and the binding site level accuracy are very low, while the motif level accuracy is relatively high, which indicates that the algorithms can usually capture at least one correct motif in an input sequence. To exploit diverse predictions from multiple runs of one or more algorithms, a consensus ensemble algorithm has been developed, which achieved 6-45% improvement over the base algorithms by increasing both the sensitivity and specificity. Our study illustrates limitations and potentials of existing sequence-based motif discovery algorithms. Taking advantage of the revealed potentials, several promising directions for further improvements are discussed. Since the sequence-based algorithms are the baseline of most of the modern motif discovery algorithms, this paper suggests substantial improvements would be possible for them.
