361 research outputs found
Technology dictates algorithms: Recent developments in read alignment
Massively parallel sequencing techniques have revolutionized biological and
medical sciences by providing unprecedented insight into the genomes of humans,
animals, and microbes. Modern sequencing platforms generate enormous amounts of
genomic data in the form of nucleotide sequences or reads. Aligning reads onto
reference genomes enables the identification of individual-specific genetic
variants and is an essential step of the majority of genomic analysis
pipelines. Aligned reads are essential for answering important biological
questions, such as detecting mutations driving various human diseases and
complex traits as well as identifying species present in metagenomic samples.
The read alignment problem is extremely challenging due to the large size of
analyzed datasets and numerous technological limitations of sequencing
platforms, and researchers have developed novel bioinformatics algorithms to
tackle these difficulties. Importantly, computational algorithms have evolved
and diversified in accordance with technological advances, leading to todays
diverse array of bioinformatics tools. Our review provides a survey of
algorithmic foundations and methodologies across 107 alignment methods
published between 1988 and 2020, for both short and long reads. We provide
rigorous experimental evaluation of 11 read aligners to demonstrate the effect
of these underlying algorithms on speed and efficiency of read aligners. We
separately discuss how longer read lengths produce unique advantages and
limitations to read alignment techniques. We also discuss how general alignment
algorithms have been tailored to the specific needs of various domains in
biology, including whole transcriptome, adaptive immune repertoire, and human
microbiome studies
BLEND: A Fast, Memory-Efficient, and Accurate Mechanism to Find Fuzzy Seed Matches
Generating the hash values of short subsequences, called seeds, enables
quickly identifying similarities between genomic sequences by matching seeds
with a single lookup of their hash values. However, these hash values can be
used only for finding exact-matching seeds as the conventional hashing methods
assign distinct hash values for different seeds, including highly similar
seeds. Finding only exact-matching seeds causes either 1) increasing the use of
the costly sequence alignment or 2) limited sensitivity.
We introduce BLEND, the first efficient and accurate mechanism that can
identify both exact-matching and highly similar seeds with a single lookup of
their hash values, called fuzzy seeds matches. BLEND 1) utilizes a technique
called SimHash, that can generate the same hash value for similar sets, and 2)
provides the proper mechanisms for using seeds as sets with the SimHash
technique to find fuzzy seed matches efficiently.
We show the benefits of BLEND when used in read overlapping and read mapping.
For read overlapping, BLEND is faster by 2.6x-63.5x (on average 19.5x), has a
lower memory footprint by 0.9x-9.7x (on average 3.6x), and finds higher quality
overlaps leading to accurate de novo assemblies than the state-of-the-art tool,
minimap2. For read mapping, BLEND is faster by 0.7x-3.7x (on average 1.7x) than
minimap2. Source code is available at https://github.com/CMU-SAFARI/BLEND
Scalable global alignment for multiple biological networks
<p>Abstract</p> <p>Background</p> <p>Advances in high-throughput technology has led to an increased amount of available data on protein-protein interaction (PPI) data. Detecting and extracting functional modules that are common across multiple networks is an important step towards understanding the role of functional modules and how they have evolved across species. A global protein-protein interaction network alignment algorithm attempts to find such functional orthologs across multiple networks.</p> <p>Results</p> <p>In this article, we propose a scalable global network alignment algorithm based on clustering methods and graph matching techniques in order to detect conserved interactions while simultaneously attempting to maximize the sequence similarity of nodes involved in the alignment. We present an algorithm for multiple alignments, in which several PPI networks are aligned. We empirically evaluated our algorithm on three real biological datasets with 6 different species and found that our approach offers a significant benefit both in terms of quality as well as speed over the current state-of-the-art algorithms.</p> <p>Conclusion</p> <p>Computational experiments on the real datasets demonstrate that our multiple network alignment algorithm is a more efficient and effective algorithm than the state-of-the-art algorithm, IsoRankN. From a qualitative standpoint, our approach also offers a significant advantage over IsoRankN for the multiple network alignment problem.</p
Entropy-scaling search of massive biological data
Many datasets exhibit a well-defined structure that can be exploited to
design faster search tools, but it is not always clear when such acceleration
is possible. Here, we introduce a framework for similarity search based on
characterizing a dataset's entropy and fractal dimension. We prove that
searching scales in time with metric entropy (number of covering hyperspheres),
if the fractal dimension of the dataset is low, and scales in space with the
sum of metric entropy and information-theoretic entropy (randomness of the
data). Using these ideas, we present accelerated versions of standard tools,
with no loss in specificity and little loss in sensitivity, for use in three
domains---high-throughput drug screening (Ammolite, 150x speedup), metagenomics
(MICA, 3.5x speedup of DIAMOND [3,700x BLASTX]), and protein structure search
(esFragBag, 10x speedup of FragBag). Our framework can be used to achieve
"compressive omics," and the general theory can be readily applied to data
science problems outside of biology.Comment: Including supplement: 41 pages, 6 figures, 4 tables, 1 bo
Murasaki: A Fast, Parallelizable Algorithm to Find Anchors from Multiple Genomes
BACKGROUND: With the number of available genome sequences increasing rapidly, the magnitude of sequence data required for multiple-genome analyses is a challenging problem. When large-scale rearrangements break the collinearity of gene orders among genomes, genome comparison algorithms must first identify sets of short well-conserved sequences present in each genome, termed anchors. Previously, anchor identification among multiple genomes has been achieved using pairwise alignment tools like BLASTZ through progressive alignment tools like TBA, but the computational requirements for sequence comparisons of multiple genomes quickly becomes a limiting factor as the number and scale of genomes grows. METHODOLOGY/PRINCIPAL FINDINGS: Our algorithm, named Murasaki, makes it possible to identify anchors within multiple large sequences on the scale of several hundred megabases in few minutes using a single CPU. Two advanced features of Murasaki are (1) adaptive hash function generation, which enables efficient use of arbitrary mismatch patterns (spaced seeds) and therefore the comparison of multiple mammalian genomes in a practical amount of computation time, and (2) parallelizable execution that decreases the required wall-clock and CPU times. Murasaki can perform a sensitive anchoring of eight mammalian genomes (human, chimp, rhesus, orangutan, mouse, rat, dog, and cow) in 21 hours CPU time (42 minutes wall time). This is the first single-pass in-core anchoring of multiple mammalian genomes. We evaluated Murasaki by comparing it with the genome alignment programs BLASTZ and TBA. We show that Murasaki can anchor multiple genomes in near linear time, compared to the quadratic time requirements of BLASTZ and TBA, while improving overall accuracy. CONCLUSIONS/SIGNIFICANCE: Murasaki provides an open source platform to take advantage of long patterns, cluster computing, and novel hash algorithms to produce accurate anchors across multiple genomes with computational efficiency significantly greater than existing methods. Murasaki is available under GPL at http://murasaki.sourceforge.net
Opaque Service Virtualisation: A Practical Tool for Emulating Endpoint Systems
Large enterprise software systems make many complex interactions with other
services in their environment. Developing and testing for production-like
conditions is therefore a very challenging task. Current approaches include
emulation of dependent services using either explicit modelling or
record-and-replay approaches. Models require deep knowledge of the target
services while record-and-replay is limited in accuracy. Both face
developmental and scaling issues. We present a new technique that improves the
accuracy of record-and-replay approaches, without requiring prior knowledge of
the service protocols. The approach uses Multiple Sequence Alignment to derive
message prototypes from recorded system interactions and a scheme to match
incoming request messages against prototypes to generate response messages. We
use a modified Needleman-Wunsch algorithm for distance calculation during
message matching. Our approach has shown greater than 99% accuracy for four
evaluated enterprise system messaging protocols. The approach has been
successfully integrated into the CA Service Virtualization commercial product
to complement its existing techniques.Comment: In Proceedings of the 38th International Conference on Software
Engineering Companion (pp. 202-211). arXiv admin note: text overlap with
arXiv:1510.0142
NOVEL COMPUTATIONAL METHODS FOR SEQUENCING DATA ANALYSIS: MAPPING, QUERY, AND CLASSIFICATION
Over the past decade, the evolution of next-generation sequencing technology has considerably advanced the genomics research. As a consequence, fast and accurate computational methods are needed for analyzing the large data in different applications. The research presented in this dissertation focuses on three areas: RNA-seq read mapping, large-scale data query, and metagenomics sequence classification.
A critical step of RNA-seq data analysis is to map the RNA-seq reads onto a reference genome. This dissertation presents a novel splice alignment tool, MapSplice3. It achieves high read alignment and base mapping yields and is able to detect splice junctions, gene fusions, and circular RNAs comprehensively at the same time. Based on MapSplice3, we further extend a novel lightweight approach called iMapSplice that enables personalized mRNA transcriptional profiling. As huge amount of RNA-seq has been shared through public datasets, it provides invaluable resources for researchers to test hypotheses by reusing existing datasets. To meet the needs of efficiently querying large-scale sequencing data, a novel method, called SeqOthello, has been developed. It is able to efficiently query sequence k-mers against large-scale datasets and finally determines the existence of the given sequence. Metagenomics studies often generate tens of millions of reads to capture the presence of microbial organisms. Thus efficient and accurate algorithms are in high demand. In this dissertation, we introduce MetaOthello, a probabilistic hashing classifier for metagenomic sequences. It supports efficient query of a taxon using its k-mer signatures
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