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

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

A Coverage Criterion for Spaced Seeds and its Applications to Support Vector Machine String Kernels and k-Mer Distances

Spaced seeds have been recently shown to not only detect more alignments, but also to give a more accurate measure of phylogenetic distances (Boden et al., 2013, Horwege et al., 2014, Leimeister et al., 2014), and to provide a lower misclassification rate when used with Support Vector Machines (SVMs) (On-odera and Shibuya, 2013), We confirm by independent experiments these two results, and propose in this article to use a coverage criterion (Benson and Mak, 2008, Martin, 2013, Martin and No{\'e}, 2014), to measure the seed efficiency in both cases in order to design better seed patterns. We show first how this coverage criterion can be directly measured by a full automaton-based approach. We then illustrate how this criterion performs when compared with two other criteria frequently used, namely the single-hit and multiple-hit criteria, through correlation coefficients with the correct classification/the true distance. At the end, for alignment-free distances, we propose an extension by adopting the coverage criterion, show how it performs, and indicate how it can be efficiently computed.Comment: http://online.liebertpub.com/doi/abs/10.1089/cmb.2014.017

A Coverage Criterion for Spaced Seeds and its Applications to Support Vector Machine String Kernels and k-Mer Distances

Spaced seeds have been recently shown to not only detect more alignments, but also to give a more accurate measure of phylogenetic distances (Boden et al., 2013, Horwege et al., 2014, Leimeister et al., 2014), and to provide a lower misclassification rate when used with Support Vector Machines (SVMs) (On-odera and Shibuya, 2013), We confirm by independent experiments these two results, and propose in this article to use a coverage criterion (Benson and Mak, 2008, Martin, 2013, Martin and No{\'e}, 2014), to measure the seed efficiency in both cases in order to design better seed patterns. We show first how this coverage criterion can be directly measured by a full automaton-based approach. We then illustrate how this criterion performs when compared with two other criteria frequently used, namely the single-hit and multiple-hit criteria, through correlation coefficients with the correct classification/the true distance. At the end, for alignment-free distances, we propose an extension by adopting the coverage criterion, show how it performs, and indicate how it can be efficiently computed.Comment: http://online.liebertpub.com/doi/abs/10.1089/cmb.2014.017

MULTIPLE SPACED SEEDS FOR OLIGONUCLEOTIDE DESIGN

An oligonucleotide is a small piece of DNA or RNA molecule, which is designed to hybridize with a unique position in a target sequence. DNA oligonucleotides have many applications such as gene identification, PCR (polymerase chain reaction) amplification, or DNA microarrays. One of the crucial issues in designing good oligonucleotide is to minimize the chance of cross-hybridization. Various heuristic algorithms are used to filter out the unsuitable regions before checking for cross-hybridization. The most successful ones are based on seeds because of their efficiency and ability to tolerate mismatches. The quality of the seeds is essential in this process. We present a sound framework for evaluating seed quality for oligonucleotide design and show that multiple spaced seeds are expected to provide the best discrimination between oligos and non-oligos

Optimization of Discrete-parameter Multiprocessor Systems using a Novel Ergodic Interpolation Technique

Modern multi-core systems have a large number of design parameters, most of which are discrete-valued, and this number is likely to keep increasing as chip complexity rises. Further, the accurate evaluation of a potential design choice is computationally expensive because it requires detailed cycle-accurate system simulation. If the discrete parameter space can be embedded into a larger continuous parameter space, then continuous space techniques can, in principle, be applied to the system optimization problem. Such continuous space techniques often scale well with the number of parameters. We propose a novel technique for embedding the discrete parameter space into an extended continuous space so that continuous space techniques can be applied to the embedded problem using cycle accurate simulation for evaluating the objective function. This embedding is implemented using simulation-based ergodic interpolation, which, unlike spatial interpolation, produces the interpolated value within a single simulation run irrespective of the number of parameters. We have implemented this interpolation scheme in a cycle-based system simulator. In a characterization study, we observe that the interpolated performance curves are continuous, piece-wise smooth, and have low statistical error. We use the ergodic interpolation-based approach to solve a large multi-core design optimization problem with 31 design parameters. Our results indicate that continuous space optimization using ergodic interpolation-based embedding can be a viable approach for large multi-core design optimization problems.Comment: A short version of this paper will be published in the proceedings of IEEE MASCOTS 2015 conferenc

Novel computational techniques for mapping and classifying Next-Generation Sequencing data

Since their emergence around 2006, Next-Generation Sequencing technologies have been revolutionizing biological and medical research. Quickly obtaining an extensive amount of short or long reads of DNA sequence from almost any biological sample enables detecting genomic variants, revealing the composition of species in a metagenome, deciphering cancer biology, decoding the evolution of living or extinct species, or understanding human migration patterns and human history in general. The pace at which the throughput of sequencing technologies is increasing surpasses the growth of storage and computer capacities, which creates new computational challenges in NGS data processing. In this thesis, we present novel computational techniques for read mapping and taxonomic classification. With more than a hundred of published mappers, read mapping might be considered fully solved. However, the vast majority of mappers follow the same paradigm and only little attention has been paid to non-standard mapping approaches. Here, we propound the so-called dynamic mapping that we show to significantly improve the resulting alignments compared to traditional mapping approaches. Dynamic mapping is based on exploiting the information from previously computed alignments, helping to improve the mapping of subsequent reads. We provide the first comprehensive overview of this method and demonstrate its qualities using Dynamic Mapping Simulator, a pipeline that compares various dynamic mapping scenarios to static mapping and iterative referencing. An important component of a dynamic mapper is an online consensus caller, i.e., a program collecting alignment statistics and guiding updates of the reference in the online fashion. We provide Ococo, the first online consensus caller that implements a smart statistics for individual genomic positions using compact bit counters. Beyond its application to dynamic mapping, Ococo can be employed as an online SNP caller in various analysis pipelines, enabling SNP calling from a stream without saving the alignments on disk. Metagenomic classification of NGS reads is another major topic studied in the thesis. Having a database with thousands of reference genomes placed on a taxonomic tree, the task is to rapidly assign a huge amount of NGS reads to tree nodes, and possibly estimate the relative abundance of involved species. In this thesis, we propose improved computational techniques for this task. In a series of experiments, we show that spaced seeds consistently improve the classification accuracy. We provide Seed-Kraken, a spaced seed extension of Kraken, the most popular classifier at present. Furthermore, we suggest ProPhyle, a new indexing strategy based on a BWT-index, obtaining a much smaller and more informative index compared to Kraken. We provide a modified version of BWA that improves the BWT-index for a quick k-mer look-up