Inexact Local Alignment Search over Suffix Arrays

Department of Computer Science, University of Maryland, College Park, MD 20742, USA.
Proceedings. IEEE International Conference on Bioinformatics and Biomedicine 11/2009; 2009(1-4):83-97. DOI: 10.1109/BIBM.2009.25
Source: PubMed


We describe an algorithm for finding approximate seeds for DNA homology searches. In contrast to previous algorithms that use exact or spaced seeds, our approximate seeds may contain insertions and deletions. We present a generalized heuristic for finding such seeds efficiently and prove that the heuristic does not affect sensitivity. We show how to adapt this algorithm to work over the memory efficient suffix array with provably minimal overhead in running time.We demonstrate the effectiveness of our algorithm on two tasks: whole genome alignment of bacteria and alignment of the DNA sequences of 177 genes that are orthologous in human and mouse. We show our algorithm achieves better sensitivity and uses less memory than other commonly used local alignment tools.

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    • "Note that if we fail to align the first say α characters of sequence i (ith sequence in the sorted list), and the common prefix of sequence i and sequence i + 1 is longer than α, we do not need to try to align sequence i + 1 at all. The search algorithm is very similar to the algorithm in [17], except that the backtracking threshold is fixed as the given radius of the clusters. We use the ternary quick sort algorithm [18] once, in the beginning, to sort the sequences lexicographically. "
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    ABSTRACT: Clustering is a fundamental operation in the analysis of biological sequence data. New DNA sequencing technologies have dramatically increased the rate at which we can generate data, resulting in datasets that cannot be efficiently analyzed by traditional clustering methods.This is particularly true in the context of taxonomic profiling of microbial communities through direct sequencing of phylogenetic markers (e.g. 16S rRNA) - the domain that motivated the work described in this paper. Many analysis approaches rely on an initial clustering step aimed at identifying sequences that belong to the same operational taxonomic unit (OTU). When defining OTUs (which have no universally accepted definition), scientists must balance a trade-off between computational efficiency and biological accuracy, as accurately estimating an environment's phylogenetic composition requires computationally-intensive analyses. We propose that efficient and mathematically well defined clustering methods can benefit existing taxonomic profiling approaches in two ways: (i) the resulting clusters can be substituted for OTUs in certain applications; and (ii) the clustering effectively reduces the size of the data-sets that need to be analyzed by complex phylogenetic pipelines (e.g., only one sequence per cluster needs to be provided to downstream analyses). To address the challenges outlined above, we developed DNACLUST, a fast clustering tool specifically designed for clustering highly-similar DNA sequences.Given a set of sequences and a sequence similarity threshold, DNACLUST creates clusters whose radius is guaranteed not to exceed the specified threshold. Underlying DNACLUST is a greedy clustering strategy that owes its performance to novel sequence alignment and k-mer based filtering algorithms.DNACLUST can also produce multiple sequence alignments for every cluster, allowing users to manually inspect clustering results, and enabling more detailed analyses of the clustered data. We compare DNACLUST to two popular clustering tools: CD-HIT and UCLUST. We show that DNACLUST is about an order of magnitude faster than CD-HIT and UCLUST (exact mode) and comparable in speed to UCLUST (approximate mode). The performance of DNACLUST improves as the similarity threshold is increased (tight clusters) making it well suited for rapidly removing duplicates and near-duplicates from a dataset, thereby reducing the size of the data being analyzed through more elaborate approaches.
    BMC Bioinformatics 06/2011; 12(1):271. DOI:10.1186/1471-2105-12-271 · 2.58 Impact Factor
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    ABSTRACT: Sequential data is prevalent in many scientific and commercial applications such as bioinformatics, system security and networking. Similarity search has been widely studied for symbolic and time series data in which each data object is a symbol or numeric value. Textual event sequences are sequences of events, where each object is a message describing an event. For example, system logs are typical textual event sequences and each event is a textual message recording internal system operations, statuses, configuration modifications or execution errors. Similar segments of an event sequence reveals similar system behaviors in the past which are helpful for system administrators to diagnose system problems. Existing search indexing for textual data only focus on unordered data. Substring matching methods are able to efficiently find matched segments over a sequence, however, their sequences are single values rather than texts. In this paper, we propose a method, suffix matrix, for efficiently searching similar segments over textual event sequences. It provides an integration of two disparate techniques: locality-sensitive hashing and suffix arrays. This method also supports the k-dissimilar segment search. A k-dissimilar segment is a segment that has at most k dissimilar events to the query sequence. By using random sequence mask proposed in this paper, this method can have a high probability to reach all k-dissimilar segments without increasing much search cost. We conduct experiments on real system log data and the experimental results show that our proposed method outperforms alternative methods using existing techniques.
    Proceedings of the 22nd ACM international conference on Conference on information & knowledge management; 10/2013
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    ABSTRACT: DNA sequences are translated into protein coding sequences and then further assigned to protein families in metagenomic analyses, because of the need for sensitivity. However, huge amounts of sequence data create the problem that even general homology search analyses using BLASTX become difficult in terms of computational cost. We designed a new homology search algorithm that finds seed sequences based on the suffix arrays of a query and a database, and have implemented it as GHOSTX. GHOSTX achieved approximately 131-165 times acceleration over a BLASTX search at similar levels of sensitivity. GHOSTX is distributed under the BSD 2-clause license and is available for download at Currently, sequencing technology continues to improve, and sequencers are increasingly producing larger and larger quantities of data. This explosion of sequence data makes computational analysis with contemporary tools more difficult. We offer this tool as a potential solution to this problem.
    PLoS ONE 08/2014; 9(8):e103833. DOI:10.1371/journal.pone.0103833 · 3.23 Impact Factor


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