De Bruijn Graph Representation Research Articles

RNA transcription and degradation of Alu retrotransposons depends on sequence features and evolutionary history.

Alu elements are one of the most successful groups of RNA retrotransposons and make up 11% of the human genome with over 1 million individual loci. They are linked to genetic defects, increases in sequence diversity, and influence transcriptional activity. Still, their RNA metabolism is poorly understood yet. It is even unclear whether Alu elements are mostly transcribed by RNA Polymerase II or III. We have conducted a transcription shutoff experiment by α-amanitin and metabolic RNA labeling by 4-thiouridine combined with RNA fragmentation (TT-seq) and RNA-seq to shed further light on the origin and life cycle of Alu transcripts. We find that Alu RNAs are more stable than previously thought and seem to originate in part from RNA Polymerase II activity, as previous reports suggest. Their expression however seems to be independent of the transcriptional activity of adjacent genes. Furthermore, we have developed a novel statistical test for detecting the expression of quantitative trait loci in Alu elements that relies on the de Bruijn graph representation of all Alu sequences. It controls for both statistical significance and biological relevance using a tuned k-mer representation, discovering influential sequence features missed by regular motif search. In addition, we discover several point mutations using a generalized linear model, and motifs of interest, which also match transcription factor-binding motifs.

Bidirectional Variable-Order de Bruijn Graphs

Compressed suffix trees and bidirectional FM-indexes can store a set of strings and support queries that let us explore the set of substrings they contain, adding and deleting characters on both the left and right, but they can use much more space than a de Bruijn graph for the strings. Bowe et al.’s BWT-based de Bruijn graph representation (Proc. Workshop on Algorithms for Bioinformatics, pp. 225–235, 2012) can be made bidirectional as well, at the cost of increasing its space usage by a small constant, but it fixes the length of the substrings. Boucher et al. (Proc. Data Compression Conference, pp. 383–392, 2015) generalized Bowe et al.’s representation to support queries about variable-length substrings, but at the cost of bidirectionality. In this paper we show how to make Boucher et al.’s variable-order implementation of de Bruijn graphs bidirectional.

MegaGTA: a sensitive and accurate metagenomic gene-targeted assembler using iterative de Bruijn graphs

BackgroundThe recent release of the gene-targeted metagenomics assembler Xander has demonstrated that using the trained Hidden Markov Model (HMM) to guide the traversal of de Bruijn graph gives obvious advantage over other assembly methods. Xander, as a pilot study, indeed has a lot of room for improvement. Apart from its slow speed, Xander uses only 1 k-mer size for graph construction and whatever choice of k will compromise either sensitivity or accuracy. Xander uses a Bloom-filter representation of de Bruijn graph to achieve a lower memory footprint. Bloom filters bring in false positives, and it is not clear how this would impact the quality of assembly. Xander does not keep track of the multiplicity of k-mers, which would have been an effective way to differentiate between erroneous k-mers and correct k-mers.ResultsIn this paper, we present a new gene-targeted assembler MegaGTA, which attempts to improve Xander in different aspects. Quality-wise, it utilizes iterative de Bruijn graphs to take full advantage of multiple k-mer sizes to make the best of both sensitivity and accuracy. Computation-wise, it employs succinct de Bruijn graphs (SdBG) to achieve low memory footprint and high speed (the latter is benefited from a highly efficient parallel algorithm for constructing SdBG). Unlike Bloom filters, an SdBG is an exact representation of a de Bruijn graph. It enables MegaGTA to avoid false-positive contigs and to easily incorporate the multiplicity of k-mers for building better HMM model.We have compared MegaGTA and Xander on an HMP-defined mock metagenomic dataset, and showed that MegaGTA excelled in both sensitivity and accuracy. On a large rhizosphere soil metagenomic sample (327Gbp), MegaGTA produced 9.7–19.3% more contigs than Xander, and these contigs were assigned to 10–25% more gene references. In our experiments, MegaGTA, depending on the number of k-mers used, is two to ten times faster than Xander.ConclusionMegaGTA improves on the algorithm of Xander and achieves higher sensitivity, accuracy and speed. Moreover, it is capable of assembling gene sequences from ultra-large metagenomic datasets. Its source code is freely available at https://github.com/HKU-BAL/megagta .

DeBGR: an efficient and near-exact representation of the weighted de Bruijn graph.

MotivationAlmost all de novo short-read genome and transcriptome assemblers start by building a representation of the de Bruijn Graph of the reads they are given as input. Even when other approaches are used for subsequent assembly (e.g. when one is using ‘long read’ technologies like those offered by PacBio or Oxford Nanopore), efficient k-mer processing is still crucial for accurate assembly, and state-of-the-art long-read error-correction methods use de Bruijn Graphs. Because of the centrality of de Bruijn Graphs, researchers have proposed numerous methods for representing de Bruijn Graphs compactly. Some of these proposals sacrifice accuracy to save space. Further, none of these methods store abundance information, i.e. the number of times that each k-mer occurs, which is key in transcriptome assemblers.ResultsWe present a method for compactly representing the weighted de Bruijn Graph (i.e. with abundance information) with essentially no errors. Our representation yields zero errors while increasing the space requirements by less than 18–28% compared to the approximate de Bruijn graph representation in Squeakr. Our technique is based on a simple invariant that all weighted de Bruijn Graphs must satisfy, and hence is likely to be of general interest and applicable in most weighted de Bruijn Graph-based systems.Availability and implementation https://github.com/splatlab/debgr.Supplementary information Supplementary data are available at Bioinformatics online.

Computing the periods of preimages in surjective cellular automata

A basic property of one-dimensional surjective cellular automata (CA) is that any preimage of a spatially periodic configuration (SPC) is spatially periodic as well. This paper investigates the relationship between the periods of SPC and the periods of their preimages for various classes of CA. When the CA is only surjective and y is a SPC of least period p, the least periods of all preimages of y are multiples of p. By leveraging on the De Bruijn graph representation of CA, we devise a general algorithm to compute the least periods appearing in the preimages of a SPC, along with their corresponding multiplicities (i.e. how many preimages have a particular least period). Next, we consider the case of linear and bipermutive cellular automata (LBCA) defined over a finite field as state alphabet. In particular, we show an equivalence between preimages of LBCA and concatenated linear recurring sequences (LRS) that allows us to give a complete characterization of their periods. Finally, we generalize these results to LBCA defined over a finite ring as alphabet.

The khmer software package: enabling efficient nucleotide sequence analysis

The khmer package is a freely available software library for working efficiently with fixed length DNA words, or k-mers. khmer provides implementations of a probabilistic k-mer counting data structure, a compressible De Bruijn graph representation, De Bruijn graph partitioning, and digital normalization. khmer is implemented in C++ and Python, and is freely available under the BSD license at https://github.com/dib-lab/khmer/.

The khmer software package: enabling efficient nucleotide sequence analysis.

The khmer package is a freely available software library for working efficientlywith fixed length DNA words, or k-mers. khmer provides implementations of aprobabilistic k-mer counting data structure, a compressible De Bruijn graph representation,De Bruijn graph partitioning, and digital normalization. khmer is implementedin C++ and Python, and is freely available under the BSD license at https://github.com/dib-lab/khmer/.

Space-efficient and exact de Bruijn graph representation based on a Bloom filter

BackgroundThe de Bruijn graph data structure is widely used in next-generation sequencing (NGS). Many programs, e.g. de novo assemblers, rely on in-memory representation of this graph. However, current techniques for representing the de Bruijn graph of a human genome require a large amount of memory (≥30 GB).ResultsWe propose a new encoding of the de Bruijn graph, which occupies an order of magnitude less space than current representations. The encoding is based on a Bloom filter, with an additional structure to remove critical false positives.ConclusionsAn assembly software implementing this structure, Minia, performed a complete de novo assembly of human genome short reads using 5.7 GB of memory in 23 hours.