Biology subjects

Nederbragt, A. J.

Publications and source records attributed to Nederbragt, A. J..

4 recordsLinked to original sources

bioRxiv2018

NucBreak: Location of structural errors in a genome assembly by using paired-end Illumina reads

BackgroundAdvances in whole genome sequencing strategies have provided the opportunity for genomic and comparative genomic analysis of a vast variety of organisms. The analysis results are highly dependent on the quality of the genome assemblies used. Assessment of the assembly accuracy may significantly increase the reliability of the analysis results and is therefore of great importance.\n\nResultsHere, we present a new tool called NucBreak aimed at detecting structural errors in assemblies, including insertions, deletions, duplications, inversions, and different inter-and intra-chromosomal rearrangements. NucBreak analyses the alignments of reads properly mapped to an assembly and exploits information about the alternative read alignments. We have compared NucBreak with other existing assembly accuracy assessment tools, namely Pilon, REAPR, and FRCbam as well as with several structural variant detection tools, including BreakDancer, Lumpy, and Wham, by using both simulated and real datasets.\n\nConclusionsThe benchmarking results have shown that NucBreak in general predicts assembly errors of different types and sizes with relatively high sensitivity and with higher precision than the other tools. Such a balance between sensitivity and precision makes NucBreak a good alternative to the existing assembly accuracy assessment tools and SV detection tools. NucBreak is freely available at https://github.com/uio-bmi/NucBreak under the MPL license.

bioinformatics↗

bioRxiv2018

Graph Peak Caller: calling ChIP-Seq Peaks on Graph-based Reference Genomes

Graph-based representations are considered to be the future for reference genomes, as they allow integrated representation of the steadily increasing data on individual variation. Currently available tools allow de novo assembly of graph-based reference genomes, alignment of new read sets to the graph representation as well as certain analyses like variant calling and haplotyping. We here present a first method for calling ChIP-Seq peaks on read data aligned to a graph-based reference genome. The method is a graph generalization of the peak caller MACS2, and is implemented in an open source tool, Graph Peak Caller. By using the existing tool vg to build a pan-genome of Arabidopsis thaliana, we validate our approach by showing that Graph Peak Caller with a pan-genome reference graph can trace variants within peaks that are not part of the linear reference genome, and find peaks that in general are more motif-enriched than those found by MACS2.

bioinformatics↗

bioRxiv2017

Genomic architecture of codfishes featured by expansions of innate immune genes and short tandem repeats

BackgroundIncreased availability of genome assemblies for non-model organisms has resulted in invaluable biological and genomic insight into numerous vertebrates including teleosts. The sequencing and assembly of the Atlantic cod (Gadus morhua) genome and the genomes of many of its relatives (Gadiformes) demonstrated a shared loss 100 million years ago of the major histocompatibility complex (MHC) II genes. The recent publication of an improved version of the Atlantic cod genome assembly reported an extreme density of tandem repeats compared to other vertebrate genome assemblies. Highly contiguous genome assemblies are needed to further investigate the unusual immune system of the Gadiformes, and the high density of tandem repeats in this group.\n\nResultsHere, we have sequenced and assembled the genome of haddock (Melanogrammus aeglefinus) - a relative of Atlantic cod - using a combination of PacBio and Illumina reads. Comparative analyses uncover that the haddock genome contains an even higher density of tandem repeats outside and within protein coding sequences than Atlantic cod. Further, both species show an elevated number of tandem repeats in genes mainly involved in signal transduction compared to other teleosts. An in-depth characterization of the immune gene repertoire demonstrates a substantial expansion of MCHI in Atlantic cod compared to haddock. In contrast, the Toll-like receptors show a similar pattern of gene losses and expansions. For another gene family associated with the innate immune system, the NOD-like receptors (NLRs), we find a large expansion common to all teleosts, with possible lineage-specific expansions in zebrafish, stickleback and the codfishes.\n\nConclusionsThe generation of a highly contiguous genome assembly of haddock revealed that the high density of short tandem repeats as well as expanded immune gene families is not unique to Atlantic cod - but most likely a feature common to all codfishes. A shared expansion of NLR genes in teleosts suggests that the NLRs have a more substantial role in the innate immunity of teleosts than other vertebrates. Moreover, we find that high copy number genes combined with variable genome assembly qualities may impede complete characterization, i.e. the number of NLRs might be underestimates in the different teleost species.

genomics↗

bioRxiv2017

The grayling genome reveals selection on gene expression regulation after whole genome duplication

Whole genome duplication (WGD) has been a major evolutionary driver of increased genomic complexity in vertebrates. One such event occurred in the salmonid family ~80 million years ago (Ss4R) giving rise to a plethora of structural and regulatory duplicate-driven divergence, making salmonids an exemplary system to investigate the evolutionary consequences of WGD. Here, we present a draft genome assembly of European grayling (Thymallus thymallus) and use this in a comparative framework to study evolution of gene regulation following WGD. Among the Ss4R duplicates identified in European grayling and Atlantic salmon (Salmo salar), one third reflect non-neutral tissue expression evolution, with strong purifying selection, maintained over ~50 million years. Of these, the majority reflect conserved tissue regulation under strong selective constraints related to brain and neural-related functions, as well as higher-order protein-protein interactions. A small subset of the duplicates has evolved tissue regulatory expression divergence in a common ancestor, which have been subsequently conserved in both lineages, suggestive of adaptive divergence following WGD. These candidates for adaptive tissue expression divergence have elevated rates of protein coding- and promoter-sequence evolution and are enriched for immune- and lipid metabolism ontology terms. Lastly, lineage-specific duplicate divergence points towards underlying differences in adaptive pressures on expression regulation in the non-anadromous grayling versus the anadromous Atlantic salmon.\n\nOur findings enhance our understanding of the role of WGD in genome evolution and highlights cases of regulatory divergence of Ss4R duplicates, possibly related to a niche shift in early salmonid evolution.

genomics↗