scholarly journals Assembling Long Accurate Reads Using de Bruijn Graphs

2020 ◽  
Author(s):  
Anton Bankevich ◽  
Andrey Bzikadze ◽  
Mikhail Kolmogorov ◽  
Pavel A. Pevzner
Keyword(s):  
Human Genome ◽  
De Bruijn Graph ◽  
High Fidelity ◽  
High Quality ◽  
De Bruijn Graphs ◽  
String Graph ◽  
De Bruijn ◽  
Genome Assembler ◽  
Large Genomes

AbstractAlthough the de Bruijn graphs represent the basis of many genome assemblers, it remains unclear how to construct these graphs for large genomes and large k-mer sizes. This algorithmic challenge has become particularly important with the emergence of long and accurate high-fidelity (HiFi) reads that were recently utilized to generate a semi-manual telomere-to-telomere assembly of the human genome using the alternative string graph assembly approach. To enable fully automated high-quality HiFi assemblies of various genomes, we developed an efficient jumboDB algorithm for constructing the de Bruijn graph for large genomes and large k-mer sizes and the LJA genome assembler that error-corrects HiFi reads and uses jumboDB to construct the de Bruijn graph on the error-corrected reads. Since the de Bruijn graph constructed for a fixed k-mer size is typically either too tangled or too fragmented, LJA uses a new concept of a multiplex de Bruijn graph with varying k-mer sizes. We demonstrate that LJA produces contiguous assemblies of complex repetitive regions in genomes including automated assemblies of various highly-repetitive human centromeres.

scholarly journals Scalable Genome Assembly through Parallel de Bruijn Graph Construction for Multiple k-mers

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Kanak Mahadik ◽  
Christopher Wright ◽  
Milind Kulkarni ◽  
Saurabh Bagchi ◽  
Somali Chaterji
Keyword(s):  
De Novo ◽  
De Bruijn Graph ◽  
High Quality ◽  
De Bruijn Graphs ◽  
Sequencing Technologies ◽  
De Bruijn ◽  
Similar Accuracy ◽  
Valued Graph ◽  
Assembly Algorithms ◽  
Level Parallelism

Abstract Remarkable advancements in high-throughput gene sequencing technologies have led to an exponential growth in the number of sequenced genomes. However, unavailability of highly parallel and scalable de novo assembly algorithms have hindered biologists attempting to swiftly assemble high-quality complex genomes. Popular de Bruijn graph assemblers, such as IDBA-UD, generate high-quality assemblies by iterating over a set of k-values used in the construction of de Bruijn graphs (DBG). However, this process of sequentially iterating from small to large k-values slows down the process of assembly. In this paper, we propose ScalaDBG, which metamorphoses this sequential process, building DBGs for each distinct k-value in parallel. We develop an innovative mechanism to “patch” a higher k-valued graph with contigs generated from a lower k-valued graph. Moreover, ScalaDBG leverages multi-level parallelism, by both scaling up on all cores of a node, and scaling out to multiple nodes simultaneously. We demonstrate that ScalaDBG completes assembling the genome faster than IDBA-UD, but with similar accuracy on a variety of datasets (6.8X faster for one of the most complex genome in our dataset).

scholarly journals AN EFFICIENT ALGORITHM FOR CHINESE POSTMAN WALK ON BI-DIRECTED DE BRUIJN GRAPHS

2012 ◽  
Vol 04 (02) ◽  
pp. 1250019 ◽  
Author(s):  
VAMSI KUNDETI ◽  
SANGUTHEVAR RAJASEKARAN ◽  
HEIU DINH
Keyword(s):  
Time Algorithm ◽  
Sequence Assembly ◽  
Plant Genome ◽  
De Bruijn Graph ◽  
Directed Flow ◽  
De Bruijn Graphs ◽  
Short Reads ◽  
String Graph ◽  
Chinese Postman ◽  
De Bruijn

Sequence assembly from short reads is an important problem in biology. It is known that solving the sequence assembly problem exactly on a bi-directed de Bruijn graph or a string graph is intractable. However, finding a shortest double stranded DNA string (SDDNA) containing all the k-long words in the reads seems to be a good heuristic to get close to the original genome. This problem is equivalent to finding a cyclic Chinese Postman (CP) walk on the underlying unweighted bi-directed de Bruijn graph built from the reads. The Chinese Postman walk Problem (CPP) is solved by reducing it to a general bi-directed flow on this graph which runs in O(|E|2 log 2(|V|)) time. In this paper we show that the cyclic CPP on bi-directed graphs can be solved without reducing it to bi-directed flow. We present a Θ(p(|V| + |E|) log (|V|) + (d max p)3) time algorithm to solve the cyclic CPP on a weighted bi-directed de Bruijn graph, where p = max {|{v|d in (v) - d out (v) > 0}|, |{v|d in (v) - d out (v) < 0}|} and d max = max {|d in (v) - d out (v)}. Our algorithm performs asymptotically better than the bi-directed flow algorithm when the number of imbalanced nodes p is much less than the nodes in the bi-directed graph. From our experimental results on various datasets, we have noticed that the value of p/|V| lies between 0.08% and 0.13% with 95% probability. Many practical bi-directed de Bruijn graphs do not have cyclic CP walks. In such cases it is not clear how the bi-directed flow can be useful in identifying contigs. Our algorithm can handle such situations and identify maximal bi-directed sub-graphs that have CP walks. A Θ(p(|V| + |E|)) time heuristic algorithm based on these ideas has been implemented for the SDDNA problem. This algorithm was tested on short reads from a plant genome and achieves an approximation ratio of at most 1.0134. We also present a Θ((|V| + |E|) log (V)) time algorithm for the single source shortest path problem on bi-directed de Bruijn graphs, which may be of independent interest.

scholarly journals Integrating long-range connectivity information into de Bruijn graphs

2017 ◽  
Author(s):  
Isaac Turner ◽  
Kiran V Garimella ◽  
Zamin Iqbal ◽  
Gil McVean
Keyword(s):  
Data Structure ◽  
Long Range ◽  
De Bruijn Graph ◽  
Sequencing Data ◽  
Genomic Context ◽  
De Bruijn Graphs ◽  
Connectivity Information ◽  
String Graph ◽  
Free Data ◽  
De Bruijn

AbstractMotivationThe de Bruijn graph is a simple and efficient data structure that is used in many areas of sequence analysis including genome assembly, read error correction and variant calling. The data structure has a single parameter k, is straightforward to implement and is tractable for large genomes with high sequencing depth. It also enables representation of multiple samples simultaneously to facilitate comparison. However, unlike the string graph, a de Bruijn graph does not retain long range information that is inherent in the read data. For this reason, applications that rely on de Bruijn graphs can produce sub-optimal results given their input.ResultsWe present a novel assembly graph data structure: the Linked de Bruijn Graph (LdBG). Constructed by adding annotations on top of a de Bruijn graph, it stores long range connectivity information through the graph. We show that with error-free data it is possible to losslessly store and recover sequence from a Linked de Bruijn graph. With assembly simulations we demonstrate that the LdBG data structure outperforms both the de Bruijn graph and the String Graph Assembler (SGA). Finally we apply the LdBG to Klebsiella pneumoniae short read data to make large (12 kbp) variant calls, which we validate using PacBio sequencing data, and to characterise the genomic context of drug-resistance genes.AvailabilityLinked de Bruijn Graphs and associated algorithms are implemented as part of McCortex, available under the MIT license at https://github.com/mcvean/[email protected].

scholarly journals Accurate determination of node and arc multiplicities in de bruijn graphs using conditional random fields

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Aranka Steyaert ◽  
Pieter Audenaert ◽  
Jan Fostier
Keyword(s):  
Genomic Sequence ◽  
Conditional Random Field ◽  
Accurate Determination ◽  
Next Generation Sequencing Data ◽  
De Bruijn Graph ◽  
Sequencing Data ◽  
De Bruijn Graphs ◽  
Sequencing Errors ◽  
Expectation Maximisation ◽  
De Bruijn

Abstract Background De Bruijn graphs are key data structures for the analysis of next-generation sequencing data. They efficiently represent the overlap between reads and hence, also the underlying genome sequence. However, sequencing errors and repeated subsequences render the identification of the true underlying sequence difficult. A key step in this process is the inference of the multiplicities of nodes and arcs in the graph. These multiplicities correspond to the number of times each k-mer (resp. k+1-mer) implied by a node (resp. arc) is present in the genomic sequence. Determining multiplicities thus reveals the repeat structure and presence of sequencing errors. Multiplicities of nodes/arcs in the de Bruijn graph are reflected in their coverage, however, coverage variability and coverage biases render their determination ambiguous. Current methods to determine node/arc multiplicities base their decisions solely on the information in nodes and arcs individually, under-utilising the information present in the sequencing data. Results To improve the accuracy with which node and arc multiplicities in a de Bruijn graph are inferred, we developed a conditional random field (CRF) model to efficiently combine the coverage information within each node/arc individually with the information of surrounding nodes and arcs. Multiplicities are thus collectively assigned in a more consistent manner. Conclusions We demonstrate that the CRF model yields significant improvements in accuracy and a more robust expectation-maximisation parameter estimation. True k-mers can be distinguished from erroneous k-mers with a higher F1 score than existing methods. A C++11 implementation is available at https://github.com/biointec/detoxunder the GNU AGPL v3.0 license.

scholarly journals The Maximum Independent Sets of de Bruijn Graphs of Diameter 3

10.37236/681 ◽  
2011 ◽  
Vol 18 (1) ◽  
Author(s):  
Dustin A. Cartwright ◽  
María Angélica Cueto ◽  
Enrique A. Tobis
Keyword(s):  
Recurrence Relation ◽  
Generating Function ◽  
Independent Sets ◽  
De Bruijn Graph ◽  
Alphabet Size ◽  
De Bruijn Graphs ◽  
Exponential Generating Function ◽  
De Bruijn

The nodes of the de Bruijn graph $B(d,3)$ consist of all strings of length $3$, taken from an alphabet of size $d$, with edges between words which are distinct substrings of a word of length $4$. We give an inductive characterization of the maximum independent sets of the de Bruijn graphs $B(d,3)$ and for the de Bruijn graph of diameter three with loops removed, for arbitrary alphabet size. We derive a recurrence relation and an exponential generating function for their number. This recurrence allows us to construct exponentially many comma-free codes of length 3 with maximal cardinality.

scholarly journals Scalable multiple whole-genome alignment and locally collinear block construction with SibeliaZ

2019 ◽  
Author(s):  
Ilia Minkin ◽  
Paul Medvedev
Keyword(s):  
Single Machine ◽  
De Bruijn Graph ◽  
Genome Alignment ◽  
Whole Genome ◽  
Reconstruction Algorithms ◽  
De Bruijn Graphs ◽  
Significant Step ◽  
De Bruijn ◽  
Whole Genome Alignment ◽  
Computational Resources

AbstractMultiple whole-genome alignment is a challenging problem in bioinformatics. Despite many successes, current methods are not able to keep up with the growing number, length, and complexity of assembled genomes, especially when computational resources are limited. Approaches based on compacted de Bruijn graphs to identify and extend anchors into locally collinear blocks have potential for scalability, but current methods do not scale to mammalian genomes. We present an algorithm, SibeliaZ-LCB, for identifying collinear blocks in closely related genomes based on analysis of the de Bruijn graph. We further incorporate this into a multiple whole-genome alignment pipeline called SibeliaZ. SibeliaZ shows run-time improvements over other methods while maintaining accuracy. On sixteen recently-assembled strains of mice, SibeliaZ runs in under 16 hours on a single machine, while other tools did not run to completion for eight mice within a week. SibeliaZ makes a significant step towards improving scalability of multiple whole-genome alignment and collinear block reconstruction algorithms on a single machine.

scholarly journals Buffering Updates Enables Efficient Dynamic de Bruijn Graphs

2021 ◽  
Author(s):  
Jarno Alanko ◽  
Bahar Alipanahi ◽  
Jonathen Settle ◽  
Christina Boucher ◽  
Travis Gagie
Keyword(s):  
Graph Model ◽  
Biological Data ◽  
Theory And Practice ◽  
De Bruijn Graph ◽  
Efficient Manner ◽  
De Bruijn Graphs ◽  
Trade Offs ◽  
Order Of Magnitude ◽  
Efficient Data ◽  
De Bruijn

AbstractMotivationThe de Bruijn graph has become a ubiquitous graph model for biological data ever since its initial introduction in the later 1990s. It has been used for a variety of purposes including genome assembly (Zerbino and Birney, 2008; Bankevich et al., 2012b; Peng et al., 2012), variant detection (Alipanahi et al., 2020b; Iqbal et al., 2012), and storage of assembled genomes (Chikhi et al., 2016). For this reason, there have been over a dozen methods for building and representing the de Bruijn graph and its variants in a space- and time-efficient manner.ResultsAlthough there exists a plethora of space efficient data structures for storing the de Bruijn graph, the majority of them make a compression-mutability trade-off. In particular, with the exception of a few methods (Muggli et al., 2019; Holley and Melsted, 2020; Crawford et al., 2018), compressed and compact de Bruijn graphs do not allow for the graph to be efficiently updated, allowing for data to be added or deleted. The most recent compressed dynamic de Bruijn graph, (Alipanahi et al., 2020a), relies on dynamic bit vectors, which are slow in theory and practice. To address this shortcoming, we present BufBOSS which is a compressed dynamic de Bruijn graph that removes the necessity of dynamic bit vectors by buffering data that should be added or removed from the graph. We implement our method, which we refer to as BufBOSS, and compare its performance to Bifrost, DynamicBOSS, and FDBG. Our experiments demonstrate that BufBOSS achieves attractive trade-offs compared to other tools in terms of time, memory and disk, and has the best deletion performance by an order of magnitude out of all the tools that are able to perform deletions. Our implementation is available at https://github.com/jnalanko/[email protected]

scholarly journals Clover: a clustering-oriented de novo assembler for Illumina sequences

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Ming-Feng Hsieh ◽  
Chin Lung Lu ◽  
Chuan Yi Tang
Keyword(s):  
De Novo Assembly ◽  
De Novo ◽  
Low Cost ◽  
De Bruijn Graph ◽  
Illumina Platform ◽  
Sequencing Errors ◽  
Sequencing Technologies ◽  
String Graph ◽  
Clustering Approach ◽  
De Bruijn

Abstract Background Next-generation sequencing technologies revolutionized genomics by producing high-throughput reads at low cost, and this progress has prompted the recent development of de novo assemblers. Multiple assembly methods based on de Bruijn graph have been shown to be efficient for Illumina reads. However, the sequencing errors generated by the sequencer complicate analysis of de novo assembly and influence the quality of downstream genomic researches. Results In this paper, we develop a de Bruijn assembler, called Clover (clustering-oriented de novo assembler), that utilizes a novel k-mer clustering approach from the overlap-layout-consensus concept to deal with the sequencing errors generated by the Illumina platform. We further evaluate Clover’s performance against several de Bruijn graph assemblers (ABySS, SOAPdenovo, SPAdes and Velvet), overlap-layout-consensus assemblers (Bambus2, CABOG and MSR-CA) and string graph assembler (SGA) on three datasets (Staphylococcus aureus, Rhodobacter sphaeroides and human chromosome 14). The results show that Clover achieves a superior assembly quality in terms of corrected N50 and E-size while remaining a significantly competitive in run time except SOAPdenovo. In addition, Clover was involved in the sequencing projects of bacterial genomes Acinetobacter baumannii TYTH-1 and Morganella morganii KT. Conclusions The marvel clustering-based approach of Clover that integrates the flexibility of the overlap-layout-consensus approach and the efficiency of the de Bruijn graph method has high potential on de novo assembly. Now, Clover is freely available as open source software from https://oz.nthu.edu.tw/~d9562563/src.html.

scholarly journals cloudSPAdes: assembly of synthetic long reads using de Bruijn graphs

2019 ◽  
Vol 35 (14) ◽  
pp. i61-i70 ◽  
Author(s):  
Ivan Tolstoganov ◽  
Anton Bankevich ◽  
Zhoutao Chen ◽  
Pavel A Pevzner
Keyword(s):  
Narrow Range ◽  
State Of The Art ◽  
Supplementary Information ◽  
De Bruijn Graph ◽  
Hybrid Assembly ◽  
De Bruijn Graphs ◽  
Long Reads ◽  
Long Read ◽  
De Bruijn ◽  
New Applications

Abstract Motivation The recently developed barcoding-based synthetic long read (SLR) technologies have already found many applications in genome assembly and analysis. However, although some new barcoding protocols are emerging and the range of SLR applications is being expanded, the existing SLR assemblers are optimized for a narrow range of parameters and are not easily extendable to new barcoding technologies and new applications such as metagenomics or hybrid assembly. Results We describe the algorithmic challenge of the SLR assembly and present a cloudSPAdes algorithm for SLR assembly that is based on analyzing the de Bruijn graph of SLRs. We benchmarked cloudSPAdes across various barcoding technologies/applications and demonstrated that it improves on the state-of-the-art SLR assemblers in accuracy and speed. Availability and implementation Source code and installation manual for cloudSPAdes are available at https://github.com/ablab/spades/releases/tag/cloudspades-paper. Supplementary Information Supplementary data are available at Bioinformatics online.

Sign in / Sign up

Export Citation Format

Share Document