4,904 research outputs found
Designing seeds for similarity search in genomic DNA
AbstractLarge-scale comparison of genomic DNA is of fundamental importance in annotating functional elements of genomes. To perform large comparisons efficiently, BLAST (Methods: Companion Methods Enzymol 266 (1996) 460, J. Mol. Biol. 215 (1990) 403, Nucleic Acids Res. 25(17) (1997) 3389) and other widely used tools use seeded alignment, which compares only sequences that can be shown to share a common pattern or “seed’’ of matching bases. The literature suggests that the choice of seed substantially affects the sensitivity of seeded alignment, but designing and evaluating seeds is computationally challenging.This work addresses the problem of designing a seed to optimize performance of seeded alignment. We give a fast, simple algorithm based on finite automata for evaluating the sensitivity of a seed in a Markov model of ungapped alignments, along with extensions to mixtures and inhomogeneous Markov models. We give intuition and theoretical results on which seeds are good choices. Finally, we describe Mandala, a software tool for seed design, and show that it can be used to improve the sensitivity of alignment in practice
Spaced seeds improve k-mer-based metagenomic classification
Metagenomics is a powerful approach to study genetic content of environmental
samples that has been strongly promoted by NGS technologies. To cope with
massive data involved in modern metagenomic projects, recent tools [4, 39] rely
on the analysis of k-mers shared between the read to be classified and sampled
reference genomes. Within this general framework, we show in this work that
spaced seeds provide a significant improvement of classification accuracy as
opposed to traditional contiguous k-mers. We support this thesis through a
series a different computational experiments, including simulations of
large-scale metagenomic projects. Scripts and programs used in this study, as
well as supplementary material, are available from
http://github.com/gregorykucherov/spaced-seeds-for-metagenomics.Comment: 23 page
Efficient seeding techniques for protein similarity search
We apply the concept of subset seeds proposed in [1] to similarity search in
protein sequences. The main question studied is the design of efficient seed
alphabets to construct seeds with optimal sensitivity/selectivity trade-offs.
We propose several different design methods and use them to construct several
alphabets.We then perform an analysis of seeds built over those alphabet and
compare them with the standard Blastp seeding method [2,3], as well as with the
family of vector seeds proposed in [4]. While the formalism of subset seed is
less expressive (but less costly to implement) than the accumulative principle
used in Blastp and vector seeds, our seeds show a similar or even better
performance than Blastp on Bernoulli models of proteins compatible with the
common BLOSUM62 matrix
Efficient seeding techniques for protein similarity search
We apply the concept of subset seeds proposed in [1] to similarity search in
protein sequences. The main question studied is the design of efficient seed
alphabets to construct seeds with optimal sensitivity/selectivity trade-offs.
We propose several different design methods and use them to construct several
alphabets.We then perform an analysis of seeds built over those alphabet and
compare them with the standard Blastp seeding method [2,3], as well as with the
family of vector seeds proposed in [4]. While the formalism of subset seed is
less expressive (but less costly to implement) than the accumulative principle
used in Blastp and vector seeds, our seeds show a similar or even better
performance than Blastp on Bernoulli models of proteins compatible with the
common BLOSUM62 matrix
A unifying framework for seed sensitivity and its application to subset seeds
We propose a general approach to compute the seed sensitivity, that can be
applied to different definitions of seeds. It treats separately three
components of the seed sensitivity problem -- a set of target alignments, an
associated probability distribution, and a seed model -- that are specified by
distinct finite automata. The approach is then applied to a new concept of
subset seeds for which we propose an efficient automaton construction.
Experimental results confirm that sensitive subset seeds can be efficiently
designed using our approach, and can then be used in similarity search
producing better results than ordinary spaced seeds
RasBhari: optimizing spaced seeds for database searching, read mapping and alignment-free sequence comparison
Many algorithms for sequence analysis rely on word matching or word
statistics. Often, these approaches can be improved if binary patterns
representing match and don't-care positions are used as a filter, such that
only those positions of words are considered that correspond to the match
positions of the patterns. The performance of these approaches, however,
depends on the underlying patterns. Herein, we show that the overlap complexity
of a pattern set that was introduced by Ilie and Ilie is closely related to the
variance of the number of matches between two evolutionarily related sequences
with respect to this pattern set. We propose a modified hill-climbing algorithm
to optimize pattern sets for database searching, read mapping and
alignment-free sequence comparison of nucleic-acid sequences; our
implementation of this algorithm is called rasbhari. Depending on the
application at hand, rasbhari can either minimize the overlap complexity of
pattern sets, maximize their sensitivity in database searching or minimize the
variance of the number of pattern-based matches in alignment-free sequence
comparison. We show that, for database searching, rasbhari generates pattern
sets with slightly higher sensitivity than existing approaches. In our Spaced
Words approach to alignment-free sequence comparison, pattern sets calculated
with rasbhari led to more accurate estimates of phylogenetic distances than the
randomly generated pattern sets that we previously used. Finally, we used
rasbhari to generate patterns for short read classification with CLARK-S. Here
too, the sensitivity of the results could be improved, compared to the default
patterns of the program. We integrated rasbhari into Spaced Words; the source
code of rasbhari is freely available at http://rasbhari.gobics.de
SEED: efficient clustering of next-generation sequences.
MotivationSimilarity clustering of next-generation sequences (NGS) is an important computational problem to study the population sizes of DNA/RNA molecules and to reduce the redundancies in NGS data. Currently, most sequence clustering algorithms are limited by their speed and scalability, and thus cannot handle data with tens of millions of reads.ResultsHere, we introduce SEED-an efficient algorithm for clustering very large NGS sets. It joins sequences into clusters that can differ by up to three mismatches and three overhanging residues from their virtual center. It is based on a modified spaced seed method, called block spaced seeds. Its clustering component operates on the hash tables by first identifying virtual center sequences and then finding all their neighboring sequences that meet the similarity parameters. SEED can cluster 100 million short read sequences in <4 h with a linear time and memory performance. When using SEED as a preprocessing tool on genome/transcriptome assembly data, it was able to reduce the time and memory requirements of the Velvet/Oasis assembler for the datasets used in this study by 60-85% and 21-41%, respectively. In addition, the assemblies contained longer contigs than non-preprocessed data as indicated by 12-27% larger N50 values. Compared with other clustering tools, SEED showed the best performance in generating clusters of NGS data similar to true cluster results with a 2- to 10-fold better time performance. While most of SEED's utilities fall into the preprocessing area of NGS data, our tests also demonstrate its efficiency as stand-alone tool for discovering clusters of small RNA sequences in NGS data from unsequenced organisms.AvailabilityThe SEED software can be downloaded for free from this site: http://manuals.bioinformatics.ucr.edu/home/[email protected] informationSupplementary data are available at Bioinformatics online
Estimating seed sensitivity on homogeneous alignments
We address the problem of estimating the sensitivity of seed-based similarity
search algorithms. In contrast to approaches based on Markov models [18, 6, 3,
4, 10], we study the estimation based on homogeneous alignments. We describe an
algorithm for counting and random generation of those alignments and an
algorithm for exact computation of the sensitivity for a broad class of seed
strategies. We provide experimental results demonstrating a bias introduced by
ignoring the homogeneousness condition
Choosing the best heuristic for seeded alignment of DNA sequences
BACKGROUND: Seeded alignment is an important component of algorithms for fast, large-scale DNA similarity search. A good seed matching heuristic can reduce the execution time of genomic-scale sequence comparison without degrading sensitivity. Recently, many types of seed have been proposed to improve on the performance of traditional contiguous seeds as used in, e.g., NCBI BLASTN. Choosing among these seed types, particularly those that use information besides the presence or absence of matching residue pairs, requires practical guidance based on a rigorous comparison, including assessment of sensitivity, specificity, and computational efficiency. This work performs such a comparison, focusing on alignments in DNA outside widely studied coding regions. RESULTS: We compare seeds of several types, including those allowing transition mutations rather than matches at fixed positions, those allowing transitions at arbitrary positions ("BLASTZ" seeds), and those using a more general scoring matrix. For each seed type, we use an extended version of our Mandala seed design software to choose seeds with optimized sensitivity for various levels of specificity. Our results show that, on a test set biased toward alignments of noncoding DNA, transition information significantly improves seed performance, while finer distinctions between different types of mismatches do not. BLASTZ seeds perform especially well. These results depend on properties of our test set that are not shared by EST-based test sets with a strong bias toward coding DNA. CONCLUSION: Practical seed design requires careful attention to the properties of the alignments being sought. For noncoding DNA sequences, seeds that use transition information, especially BLASTZ-style seeds, are particularly useful. The Mandala seed design software can be found at
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