scholarly journals MUM&Co: accurate detection of all SV types through whole-genome alignment

2020 ◽  
Vol 36 (10) ◽  
pp. 3242-3243 ◽  
Author(s):  
Samuel O’Donnell ◽  
Gilles Fischer
Keyword(s):  
De Novo ◽  
Supplementary Information ◽  
Genome Alignment ◽  
Whole Genome ◽  
Structural Variations ◽  
Sequencing Technologies ◽  
Third Generation Sequencing ◽  
Human Genomes ◽  
Whole Genome Alignment ◽  
Primary Output

Abstract Summary MUM&Co is a single bash script to detect structural variations (SVs) utilizing whole-genome alignment (WGA). Using MUMmer’s nucmer alignment, MUM&Co can detect insertions, deletions, tandem duplications, inversions and translocations greater than 50 bp. Its versatility depends upon the WGA and therefore benefits from contiguous de-novo assemblies generated by third generation sequencing technologies. Benchmarked against five WGA SV-calling tools, MUM&Co outperforms all tools on simulated SVs in yeast, plant and human genomes and performs similarly in two real human datasets. Additionally, MUM&Co is particularly unique in its ability to find inversions in both simulated and real datasets. Lastly, MUM&Co’s primary output is an intuitive tabulated file containing a list of SVs with only necessary genomic details. Availability and implementation https://github.com/SAMtoBAM/MUMandCo. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals Scalable multi whole-genome alignment using recursive exact matching

2015 ◽  
Author(s):  
Jasper Linthorst ◽  
Marc Hulsman ◽  
Henne Holstege ◽  
Marcel Reinders
Keyword(s):  
De Novo ◽  
Genome Alignment ◽  
Exact Matching ◽  
Structural Variations ◽  
De Novo Genome Assembly ◽  
Sequencing Technologies ◽  
Third Generation Sequencing ◽  
Computational Performance ◽  
Human Genomes ◽  
Novel Concept

The emergence of third generation sequencing technologies has brought near perfect de-novo genome assembly within reach. This clears the way towards reference-free detection of genomic variations. In this paper, we introduce a novel concept for aligning whole-genomes which allows the alignment of multiple genomes. Alignments are constructed in a recursive manner, in which alignment decisions are statistically supported. Computational performance is achieved by splitting an initial indexing data structure into a multitude of smaller indices. We show that our method can be used to detect high resolution structural variations between two human genomes, and that it can be used to obtain a high quality multiple genome alignment of at least nineteen Mycobacterium tuberculosis genomes. An implementation of the outlined algorithm called REVEAL is available on: https://github.com/jasperlinthorst/REVEAL

scholarly journals A study of transposable element-associated structural variations (TASVs) using a de novo-assembled Korean genome

2021 ◽  
Author(s):  
Seyoung Mun ◽  
Songmi Kim ◽  
Wooseok Lee ◽  
Keunsoo Kang ◽  
Thomas J. Meyer ◽  
...  
Keyword(s):  
Genome Sequencing ◽  
Genome Assembly ◽  
De Novo ◽  
Personal Genome ◽  
Human Populations ◽  
Whole Genome ◽  
Structural Variations ◽  
Insert Size ◽  
Human Genomes ◽  
Next Generation Sequencing Ngs

AbstractAdvances in next-generation sequencing (NGS) technology have made personal genome sequencing possible, and indeed, many individual human genomes have now been sequenced. Comparisons of these individual genomes have revealed substantial genomic differences between human populations as well as between individuals from closely related ethnic groups. Transposable elements (TEs) are known to be one of the major sources of these variations and act through various mechanisms, including de novo insertion, insertion-mediated deletion, and TE–TE recombination-mediated deletion. In this study, we carried out de novo whole-genome sequencing of one Korean individual (KPGP9) via multiple insert-size libraries. The de novo whole-genome assembly resulted in 31,305 scaffolds with a scaffold N50 size of 13.23 Mb. Furthermore, through computational data analysis and experimental verification, we revealed that 182 TE-associated structural variation (TASV) insertions and 89 TASV deletions contributed 64,232 bp in sequence gain and 82,772 bp in sequence loss, respectively, in the KPGP9 genome relative to the hg19 reference genome. We also verified structural differences associated with TASVs by comparative analysis with TASVs in recent genomes (AK1 and TCGA genomes) and reported their details. Here, we constructed a new Korean de novo whole-genome assembly and provide the first study, to our knowledge, focused on the identification of TASVs in an individual Korean genome. Our findings again highlight the role of TEs as a major driver of structural variations in human individual genomes.

scholarly journals seq-seq-pan: Building a computational pan-genome data structure on whole genome alignment

2017 ◽  
Author(s):  
Christine Jandrasits ◽  
Piotr W Dabrowski ◽  
Stephan Fuchs ◽  
Bernhard Y Renard
Keyword(s):  
Current Approach ◽  
Reference Sequence ◽  
Genome Alignment ◽  
Whole Genome ◽  
Genome Data ◽  
Sequencing Technologies ◽  
Full Diversity ◽  
Constant Change ◽  
Whole Genome Alignment ◽  
Multiple Sequences

AbstractBackgroundThe increasing application of next generation sequencing technologies has led to the availability of thousands of reference genomes, often providing multiple genomes for the same or closely related species. The current approach to represent a species or a population with a single reference sequence and a set of variations cannot represent their full diversity and introduces bias towards the chosen reference. There is a need for the representation of multiple sequences in a composite way that is compatible with existing data sources for annotation and suitable for established sequence analysis methods. At the same time, this representation needs to be easily accessible and extendable to account for the constant change of available genomes.ResultsWe introduce seq-seq-pan, a framework that provides methods for adding or removing new genomes from a set of aligned genomes and uses these to construct a whole genome alignment. Throughout the sequential workflow the alignment is optimized for generating a representative linear presentation of the aligned set of genomes, that enables its usage for annotation and in downstream analyses.ConclusionsBy providing dynamic updates and optimized processing, our approach enables the usage of whole genome alignment in the field of pan-genomics. In addition, the sequential workflow can be used as a fast alternative to existing whole genome aligners. seq-seq-pan is freely available at https://gitlab.com/groups/rki_bioinformatics

scholarly journals Detection and assembly of novel sequence insertions using Linked-Read technology

2019 ◽  
Author(s):  
Dmitry Meleshko ◽  
Patrick Marks ◽  
Stephen Williams ◽  
Iman Hajirasouliha
Keyword(s):  
Dna Sequences ◽  
De Novo Assembly ◽  
De Novo ◽  
Supplementary Information ◽  
Computational Techniques ◽  
Whole Genome ◽  
Structural Variations ◽  
Short Read ◽  
Link Type ◽  
Long Read

AbstractMotivationEmerging Linked-Read (aka read-cloud) technologies such as the 10x Genomics Chromium system have great potential for accurate detection and phasing of largescale human genome structural variations (SVs). By leveraging the long-range information encoded in Linked-Read sequencing, computational techniques are able to detect and characterize complex structural variations that are previously undetectable by short-read methods. However, there is no available Linked-Read method for detection and assembly of novel sequence insertions, DNA sequences present in a given sequenced sample but missing in the reference genome, without requiring whole genome de novo assembly. In this paper, we propose a novel integrated alignment-based and local-assembly-based algorithm, Novel-X, that effectively uses the barcode information encoded in Linked-Read sequencing datasets to improve detection of such events without the need of whole genome de novo assembly. We evaluated our method on two haploid human genomes, CHM1 and CHM13, sequenced on the 10x Genomics Chromium system. These genomes have been also characterized with high coverage PacBio long-reads recently. We also tested our method on NA12878, the wellknown HapMap CEPH diploid genome and the child genome in a Yoruba trio (NA19240) which was recently studied on multiple sequencing platforms. Detecting insertion events is very challenging using short reads and the only viable available solution is by long-read sequencing (e.g. PabBio or ONT). Our experiments, however, show that Novel-X finds many insertions that cannot be found by state of the art tools using short-read sequencing data but present in PacBio data. Since Linked-Read sequencing is significantly cheaper than long-read sequencing, our method using Linked-Reads enables routine large-scale screenings of sequenced genomes for novel sequence insertions.AvailabilitySoftware is freely available at https://github.com/1dayac/[email protected] informationSupplementary data are available at https://github.com/1dayac/novel_insertions_supplementary

scholarly journals Progressive Cactus is a multiple-genome aligner for the thousand-genome era

Nature ◽  
2020 ◽  
Vol 587 (7833) ◽  
pp. 246-251 ◽  
Author(s):  
Joel Armstrong ◽  
Glenn Hickey ◽  
Mark Diekhans ◽  
Ian T. Fiddes ◽  
Adam M. Novak ◽  
...  
Keyword(s):  
Large Scale ◽  
De Novo ◽  
Genome Alignment ◽  
Vertebrate Genome ◽  
Multiple Genome ◽  
Sequencing Technologies ◽  
Third Generation Sequencing ◽  
Genome Assemblies ◽  
Information Database ◽  
Generation Sequencing

AbstractNew genome assemblies have been arriving at a rapidly increasing pace, thanks to decreases in sequencing costs and improvements in third-generation sequencing technologies1–3. For example, the number of vertebrate genome assemblies currently in the NCBI (National Center for Biotechnology Information) database4 increased by more than 50% to 1,485 assemblies in the year from July 2018 to July 2019. In addition to this influx of assemblies from different species, new human de novo assemblies5 are being produced, which enable the analysis of not only small polymorphisms, but also complex, large-scale structural differences between human individuals and haplotypes. This coming era and its unprecedented amount of data offer the opportunity to uncover many insights into genome evolution but also present challenges in how to adapt current analysis methods to meet the increased scale. Cactus6, a reference-free multiple genome alignment program, has been shown to be highly accurate, but the existing implementation scales poorly with increasing numbers of genomes, and struggles in regions of highly duplicated sequences. Here we describe progressive extensions to Cactus to create Progressive Cactus, which enables the reference-free alignment of tens to thousands of large vertebrate genomes while maintaining high alignment quality. We describe results from an alignment of more than 600 amniote genomes, which is to our knowledge the largest multiple vertebrate genome alignment created so far.

scholarly journals Discrimination of hospital isolates of Acinetobacter baumannii using repeated sequences and whole genome alignment differential analysis

2021 ◽  
Author(s):  
Roman Kotłowski ◽  
Alicja Nowak-Zaleska ◽  
Grzegorz Węgrzyn
Keyword(s):  
Acinetobacter Baumannii ◽  
Time Frame ◽  
Repeated Sequences ◽  
Hospital Environment ◽  
Genome Alignment ◽  
Whole Genome ◽  
Differential Analysis ◽  
Gene Encoding ◽  
Resistance Patterns ◽  
Whole Genome Alignment

AbstractAn optimized method for bacterial strain differentiation, based on combination of Repeated Sequences and Whole Genome Alignment Differential Analysis (RS&WGADA), is presented in this report. In this analysis, 51 Acinetobacter baumannii multidrug-resistance strains from one hospital environment and patients from 14 hospital wards were classified on the basis of polymorphisms of repeated sequences located in CRISPR region, variation in the gene encoding the EmrA-homologue of E. coli, and antibiotic resistance patterns, in combination with three newly identified polymorphic regions in the genomes of A. baumannii clinical isolates. Differential analysis of two similarity matrices between different genotypes and resistance patterns allowed to distinguish three significant correlations (p < 0.05) between 172 bp DNA insertion combined with resistance to chloramphenicol and gentamycin. Interestingly, 45 and 55 bp DNA insertions within the CRISPR region were identified, and combined during analyses with resistance/susceptibility to trimethoprim/sulfamethoxazole. Moreover, 184 or 1374 bp DNA length polymorphisms in the genomic region located upstream of the GTP cyclohydrolase I gene, associated mainly with imipenem susceptibility, was identified. In addition, considerable nucleotide polymorphism of the gene encoding the gamma/tau subunit of DNA polymerase III, an enzyme crucial for bacterial DNA replication, was discovered. The differentiation analysis performed using the above described approach allowed us to monitor the distribution of A. baumannii isolates in different wards of the hospital in the time frame of several years, indicating that the optimized method may be useful in hospital epidemiological studies, particularly in identification of the source of primary infections.

scholarly journals Apollo: a sequencing-technology-independent, scalable and accurate assembly polishing algorithm

2020 ◽  
Vol 36 (12) ◽  
pp. 3669-3679 ◽  
Author(s):  
Can Firtina ◽  
Jeremie S Kim ◽  
Mohammed Alser ◽  
Damla Senol Cali ◽  
A Ercument Cicek ◽  
...  
Keyword(s):  
Genome Analysis ◽  
Supplementary Information ◽  
Third Generation ◽  
Sequencing Technology ◽  
Base Pairs ◽  
Sequencing Technologies ◽  
Third Generation Sequencing ◽  
Long Reads ◽  
Generation Sequencing ◽  
Large Genomes

Abstract Motivation Third-generation sequencing technologies can sequence long reads that contain as many as 2 million base pairs. These long reads are used to construct an assembly (i.e. the subject’s genome), which is further used in downstream genome analysis. Unfortunately, third-generation sequencing technologies have high sequencing error rates and a large proportion of base pairs in these long reads is incorrectly identified. These errors propagate to the assembly and affect the accuracy of genome analysis. Assembly polishing algorithms minimize such error propagation by polishing or fixing errors in the assembly by using information from alignments between reads and the assembly (i.e. read-to-assembly alignment information). However, current assembly polishing algorithms can only polish an assembly using reads from either a certain sequencing technology or a small assembly. Such technology-dependency and assembly-size dependency require researchers to (i) run multiple polishing algorithms and (ii) use small chunks of a large genome to use all available readsets and polish large genomes, respectively. Results We introduce Apollo, a universal assembly polishing algorithm that scales well to polish an assembly of any size (i.e. both large and small genomes) using reads from all sequencing technologies (i.e. second- and third-generation). Our goal is to provide a single algorithm that uses read sets from all available sequencing technologies to improve the accuracy of assembly polishing and that can polish large genomes. Apollo (i) models an assembly as a profile hidden Markov model (pHMM), (ii) uses read-to-assembly alignment to train the pHMM with the Forward–Backward algorithm and (iii) decodes the trained model with the Viterbi algorithm to produce a polished assembly. Our experiments with real readsets demonstrate that Apollo is the only algorithm that (i) uses reads from any sequencing technology within a single run and (ii) scales well to polish large assemblies without splitting the assembly into multiple parts. Availability and implementation Source code is available at https://github.com/CMU-SAFARI/Apollo. Supplementary information Supplementary data are available at Bioinformatics online.

Efficient Algorithms for Optimizing Whole Genome Alignment with Noise

2003 ◽  
pp. 364-374 ◽  
Author(s):  
T. W. Lam ◽  
N. Lu ◽  
H. F. Ting ◽  
Prudence W. H. Wong ◽  
S. M. Yiu
Keyword(s):  
Efficient Algorithms ◽  
Genome Alignment ◽  
Whole Genome ◽  
Whole Genome Alignment
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