Lex Nederbragt

• Reinar, William Brynildsen; Tørresen, Ole K.; Nederbragt, Lex; Matschiner, Michael; Jentoft, Sissel & Jakobsen, Kjetill Sigurd (2023). Teleost genomic repeat landscapes in light of diversification rates and ecology. Mobile DNA. 14(1), p. 1–12. doi: 10.1186/s13100-023-00302-9. Full text in Research Archive Show summary

  Repetitive DNA make up a considerable fraction of most eukaryotic genomes. In fish, transposable element (TE) activity has coincided with rapid species diversification. Here, we annotated the repetitive content in 100 genome assemblies, covering the major branches of the diverse lineage of teleost fish. We investigated if TE content correlates with family level net diversification rates and found support for a weak negative correlation. Further, we demonstrated that TE proportion correlates with genome size, but not to the proportion of short tandem repeats (STRs), which implies independent evolutionary paths. Marine and freshwater fish had large differences in STR content, with the most extreme propagation detected in the genomes of codfish species and Atlantic herring. Such a high density of STRs is likely to increase the mutational load, which we propose could be counterbalanced by high fecundity as seen in codfishes and herring.

• Eliassen, June Edvarda; Bøe, Maria Vetleseter; Nederbragt, Lex; Berg, Marthe Mjøen & Gregers, Tone Fredsvik (2022). Motivasjon for beregningsorientert biologi og sammenhengen med matematikk R2 fra videregående opplæring. Nordic Journal of STEM Education. 4(2), p. 58–70. doi: 10.5324/njsteme.v4i2.4026. Full text in Research Archive Show summary

  
 Programmering og modellering har i de senere år blitt innført i høyere utdanning og ble innført i skolen med fagfornyelsen fra høsten 2020. Det har skapt behov for mer kunnskap om motivasjon og læring i emner som integrerer programmering som et nytt element i ellers veletablerte fagdisipliner. Denne studien undersøkte motivasjon for beregningsorientering (programmering og modellering) ved studieprogrammet biovitenskap ved Universitetet i Oslo. Spørreundersøkelser basert på Eccles’ forventning-verdi-modell ble gjennomført ved semesterstart og -slutt i to påfølgende år, før og etter innføring av krav om matematikk R2 (R2-kravet). Motivasjonsvariabler ble validert ved faktoranalyse og undersøkelse av indre konsistens. Resultatene viste at studentene hadde lavere mestringsforventning og interesse for et emne som integrerer programmering i biologi enn for studieprogrammet generelt. Nytteverdien var den sterkeste motiverende faktoren for emnet. Studenter med matematikk R2 hadde større mestringsforventning til emnet enn de som ikke hadde denne fordypningen, og opplevde mindre utfordring med matematikk og programmering i emnet. Samtidig opplevde disse studentene større utfordring med biologien i emnet, og det viste seg at studenter med full fordypning i matematikk R2 i mindre grad enn studenter uten R2 hadde full fordypning i biologi fra videregående opplæring. Resultatene drøftes i lys av motivasjonsteori med tanke på implikasjoner for undervisning, inntakskrav og videre forskning.

• Khelik, Ksenia; Sandve, Geir Kjetil; Nederbragt, Alexander Johan & Rognes, Torbjørn (2020). NucBreak: location of structural errors in a genome assembly by using paired-end Illumina reads. BMC Bioinformatics. 21(1). doi: 10.1186/s12859-020-3414-0. Full text in Research Archive Show summary

  Background Advances 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. Results Here, we present a new tool called NucBreak aimed at localizing structural errors in assemblies, including insertions, deletions, duplications, inversions, and different inter- and intra-chromosomal rearrangements. The approach taken by existing alternative tools is based on analysing reads that do not map properly to the assembly, for instance discordantly mapped reads, soft-clipped reads and singletons. NucBreak uses an entirely different and unique method to localise the errors. It is based on analysing the alignments of reads that are properly mapped to an assembly and exploit information about the alternative read alignments. It does not annotate detected errors. 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. Conclusions The benchmarking results have shown that NucBreak in general predicts assembly errors of different types and sizes with relatively high sensitivity and with lower false discovery rate than the other tools. Such a balance between sensitivity and false discovery rate 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.

• Grytten, Ivar; Rand, Knut Dagestad; Nederbragt, Alexander Johan & Sandve, Geir Kjetil (2020). Assessing graph-based read mappers against a baseline approach highlights strengths and weaknesses of current methods. BMC Genomics. 21. doi: 10.1186/s12864-020-6685-y. Full text in Research Archive Show summary

  Background Graph-based reference genomes have become popular as they allow read mapping and follow-up analyses in settings where the exact haplotypes underlying a high-throughput sequencing experiment are not precisely known. Two recent papers show that mapping to graph-based reference genomes can improve accuracy as compared to methods using linear references. Both of these methods index the sequences for most paths up to a certain length in the graph in order to enable direct mapping of reads containing common variants. However, the combinatorial explosion of possible paths through nearby variants also leads to a huge search space and an increased chance of false positive alignments to highly variable regions. Results We here assess three prominent graph-based read mappers against a hybrid baseline approach that combines an initial path determination with a tuned linear read mapping method. We show, using a previously proposed benchmark, that this simple approach is able to improve overall accuracy of read-mapping to graph-based reference genomes. Conclusions Our method is implemented in a tool Two-step Graph Mapper, which is available at https://github.com/uio-bmi/two_step_graph_mapperalong with data and scripts for reproducing the experiments. Our method highlights characteristics of the current generation of graph-based read mappers and shows potential for improvement for future graph-based read mappers.

• Varadharajan, Srinidhi; Rastas, Pasi; Löytynoja, Ari; Matschiner, Michael; Calboli, Federico C. F. & Guo, Baocheng [Show all 9 contributors for this article] (2019). A High-Quality Assembly of the Nine-Spined Stickleback (Pungitius pungitius) Genome. Genome Biology and Evolution (GBE). 11(11), p. 3291–3308. doi: 10.1093/gbe/evz240. Full text in Research Archive Show summary

  The Gasterosteidae fish family hosts several species that are important models for eco-evolutionary, genetic and genomic research. In particular, a wealth of genetic and genomic data has been generated for the three-spined stickleback (Gasterosteus aculeatus), the ‘ecology’s supermodel’, while the genomic resources for the nine-spined stickleback (Pungitius pungitius) have remained relatively scarce. Here, we report a high-quality chromosome-level genome assembly of P. pungitius consisting of 5,303 contigs (N50 = 1.2 Mbp) with a total size of 521 Mbp. These contigs were mapped to 21 linkage groups using a high-density linkage map, yielding a final assembly with 98.5% BUSCO completeness. A total of 25,062 protein-coding genes were annotated, and ca. 23% of the assembly was found to consist of repetitive elements. A comprehensive analysis of repetitive elements uncovered centromeric-specific tandem repeats and provided insights into the evolution of retrotransposons. A multigene phylogenetic analysis inferred a divergence time of about 26 million years (MYA) between nine- and three-spined sticklebacks, which is far older than the commonly assumed estimate of 13 MYA. Compared to the three-spined stickleback, we identified an additional duplication of several genes in the hemoglobin cluster. Sequencing data from populations adapted to different environments indicated potential copy number variations in hemoglobin genes. Furthermore, genome-wide synteny comparisons between three- and nine-spined sticklebacks identified chromosomal rearrangements underlying the karyotypic differences between the two species. The high-quality chromosome-scale assembly of the nine-spined stickleback genome obtained with long-read sequencing technology provides a crucial resource for comparative and population genomic investigations of stickleback fishes and teleosts.

• Grytten, Ivar; Rand, Knut Dagestad; Nederbragt, Alexander Johan; Storvik, Geir Olve; Glad, Ingrid Kristine & Sandve, Geir Kjetil (2019). Graph Peak Caller: Calling ChIP-seq peaks on graph-based reference genomes. PLoS Computational Biology. ISSN 1553-734X. 15(2), p. 1–13. doi: 10.1371/journal.pcbi.1006731. Full text in Research Archive Show summary

  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.

• Varadharajan, Srinidhi; Sandve, Simen Rød; Gillard, Gareth Benjamin; Tørresen, Ole K.; Mulugeta, Teshome Dagne & Hvidsten, Torgeir Rhoden [Show all 11 contributors for this article] (2018). The grayling genome reveals selection on gene expression regulation after whole-genome duplication. Genome Biology and Evolution (GBE). 10(10), p. 2785–2800. doi: 10.1093/gbe/evy201. Full text in Research Archive Show summary

  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 Ma (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 nonneutral tissue expression evolution, with strong purifying selection, maintained over ∼50 Myr. 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 have 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 toward underlying differences in adaptive pressures on expression regulation in the nonanadromous grayling versus the anadromous Atlantic salmon. Our findings enhance our understanding of the role of WGD in genome evolution and highlight cases of regulatory divergence of Ss4R duplicates, possibly related to a niche shift in early salmonid evolution.

• Lie, Kai Kristoffer; Tørresen, Ole K.; Solbakken, Monica Hongrø; Rønnestad, Ivar; Tooming-Klunderud, Ave & Nederbragt, Alexander Johan [Show all 8 contributors for this article] (2018). Loss of stomach, loss of appetite? Sequencing of the ballan wrasse (Labrus bergylta) genome and intestinal transcriptomic profiling illuminate the evolution of loss of stomach function in fish. BMC Genomics. 19(186), p. 1–17. doi: 10.1186/s12864-018-4570-8. Full text in Research Archive Show summary

  Background: The ballan wrasse (Labrus bergylta) belongs to a large teleost family containing more than 600 species showing several unique evolutionary traits such as lack of stomach and hermaphroditism. Agastric fish are found throughout the teleost phylogeny, in quite diverse and unrelated lineages, indicating stomach loss has occurred independently multiple times in the course of evolution. By assembling the ballan wrasse genome and transcriptome we aimed to determine the genetic basis for its digestive system function and appetite regulation. Among other, this knowledge will aid the formulation of aquaculture diets that meet the nutritional needs of agastric species. Results: Long and short read sequencing technologies were combined to generate a ballan wrasse genome of 805 Mbp. Analysis of the genome and transcriptome assemblies confirmed the absence of genes that code for proteins involved in gastric function. The gene coding for the appetite stimulating protein ghrelin was also absent in wrasse. Gene synteny mapping identified several appetite-controlling genes and their paralogs previously undescribed in fish. Transcriptome profiling along the length of the intestine found a declining expression gradient from the anterior to the posterior, and a distinct expression profile in the hind gut. Conclusions: We showed gene loss has occurred for all known genes related to stomach function in the ballan wrasse, while the remaining functions of the digestive tract appear intact. The results also show appetite control in ballan wrasse has undergone substantial changes. The loss of ghrelin suggests that other genes, such as motilin, may play a ghrelin like role. The wrasse genome offers novel insight in to the evolutionary traits of this large family. As the stomach plays a major role in protein digestion, the lack of genes related to stomach digestion in wrasse suggests it requires formulated diets with higher levels of readily digestible protein than those for gastric species.

• Jørgensen, Tor Erik; Karlsen, Bård Ove; Emblem, Åse; Breines, Ragna; Andreassen, morten & Rounge, Trine Ballestad [Show all 15 contributors for this article] (2018). Mitochondrial genome variation of Atlantic cod. BMC Research Notes. 11:397, p. 1–7. doi: 10.1186/s13104-018-3506-3. Full text in Research Archive Show summary

  Objective:<br> The objective of this study was to analyse intraspecifc sequence variation of Atlantic cod mitochondrial DNA, based on a comprehensive collection of completely sequenced mitochondrial genomes. <br>Results:<br> We determined the complete mitochondrial DNA sequence of 124 cod specimens from the eastern and western part of the species’ distribution range in the North Atlantic Ocean. All specimens harboured a unique mitochondrial DNA haplotype. Nine hundred and ffty-two polymorphic sites were identifed, including 109 non-synonymous sites within protein coding regions. Eighteen variable sites were identifed as indels, exclusively distributed in structural RNA genes and non-coding regions. Phylogeographic analyses based on 156 available cod mitochondrial genomes did not reveal a clear structure. There was a lack of mitochondrial genetic diferentiation between two ecotypes of cod in the eastern North Atlantic, but eastern and western cod were diferentiated and mitochondrial genome diversity was higher in the eastern than the western Atlantic, suggesting deviating population histories. The geographic distribution of mitochondrial genome variation seems to be governed by demographic processes and gene fow among ecotypes that are otherwise characterized by localized genomic divergence associated with chromosomal inversions.

• Tørresen, Ole K.; Brieuc, Marine Servane; Solbakken, Monica Hongrø; Sørhus, Elin; Nederbragt, Alexander Johan & Jakobsen, Kjetill Sigurd [Show all 9 contributors for this article] (2018). Genomic architecture of haddock (Melanogrammus aeglefinus) shows expansions of innate immune genes and short tandem repeats. BMC Genomics. 19(240), p. 1–17. doi: 10.1186/s12864-018-4616-y. Full text in Research Archive Show summary

  Increased availability of genome assemblies for non-model organisms has resulted in invaluable biological and genomic insight into numerous vertebrates, including teleosts. Sequencing of the Atlantic cod (Gadus morhua) genome and the genomes of many of its relatives (Gadiformes) demonstrated a shared loss of the major histocompatibility complex (MHC) II genes 100 million years ago. An improved version of the Atlantic cod genome assembly shows an extreme density of tandem repeats compared to other vertebrate genome assemblies. Highly contiguous assemblies are therefore needed to further investigate the unusual immune system of the Gadiformes, and whether the high density of tandem repeats found in Atlantic cod is a shared trait in this group.

• Simovski, Boris; Vodak, Daniel; Gundersen, Sveinung; Domanska, Diana Ewa; Azab, Abdulrahman & Holden, Lars [Show all 25 contributors for this article] (2017). GSuite HyperBrowser: integrative analysis of dataset collections across the genome and epigenome. GigaScience. 6(7), p. 1–12. doi: 10.1093/gigascience/gix032. Full text in Research Archive Show summary

  Background: Recent large-scale undertakings such as ENCODE and Roadmap Epigenomics have generated experimental data mapped to the human reference genome (as genomic tracks) representing a variety of functional elements across a large number of cell types. Despite the high potential value of these publicly available data for a broad variety of investigations, little attention has been given to the analytical methodology necessary for their widespread utilisation. Findings: We here present a first principled treatment of the analysis of collections of genomic tracks. We have developed novel computational and statistical methodology to permit comparative and confirmatory analyses across multiple and disparate data sources. We delineate a set of generic questions that are useful across a broad range of investigations and discuss the implications of choosing different statistical measures and null models. Examples include contrasting analyses across different tissues or diseases. The methodology has been implemented in a comprehensive open-source software system, the GSuite HyperBrowser. To make the functionality accessible to biologists, and to facilitate reproducible analysis, we have also developed a web-based interface providing an expertly guided and customizable way of utilizing the methodology. With this system, many novel biological questions can flexibly be posed and rapidly answered. Conclusions: Through a combination of streamlined data acquisition, interoperable representation of dataset collections and customizable statistical analysis with guided setup and interpretation, the GSuite HyperBrowser represents a first comprehensive solution for integrative analysis of track collections across the genome and epigenome. The software is available at: https://hyperbrowser.uio.no

• Rand, Knut Dagestad; Grytten, Ivar; Nederbragt, Alexander Johan; Storvik, Geir Olve; Glad, Ingrid Kristine & Sandve, Geir Kjetil (2017). Coordinates and intervals in graph-based reference genomes. BMC Bioinformatics. 18:263, p. 1–8. doi: 10.1186/s12859-017-1678-9. Full text in Research Archive Show summary

  Background It has been proposed that future reference genomes should be graph structures in order to better represent the sequence diversity present in a species. However, there is currently no standard method to represent genomic intervals, such as the positions of genes or transcription factor binding sites, on graph-based reference genomes. Results We formalize offset-based coordinate systems on graph-based reference genomes and introduce methods for representing intervals on these reference structures. We show the advantage of our methods by representing genes on a graph-based representation of the newest assembly of the human genome (GRCh38) and its alternative loci for regions that are highly variable. Conclusion More complex reference genomes, containing alternative loci, require methods to represent genomic data on these structures. Our proposed notation for genomic intervals makes it possible to fully utilize the alternative loci of the GRCh38 assembly and potential future graph-based reference genomes. We have made a Python package for representing such intervals on offset-based coordinate systems, available at https://github.com/uio-cels/offsetbasedgraph . An interactive web-tool using this Python package to visualize genes on a graph created from GRCh38 is available at https://github.com/uio-cels/genomicgraphcoords .

• Elgvin, Tore Oldeide; Trier, Cassandra Nicole; Tørresen, Ole Kristian; Hagen, Ingerid; Lien, Sigbjørn & Nederbragt, Alexander Johan [Show all 9 contributors for this article] (2017). The genomic mosaicism of hybrid speciation. Science Advances. 3, p. 1–16. doi: 10.1126/sciadv.1602996. Full text in Research Archive Show summary

  Hybridization is widespread in nature and, in some instances, can result in the formation of a new hybrid species. We investigate the genetic foundation of this poorly understood process through whole-genome analysis of the hybrid Italian sparrow and its progenitors. We find overall balanced yet heterogeneous levels of contribution from each parent species throughout the hybrid genome and identify areas of novel divergence in the hybrid species exhibiting signals consistent with balancing selection. High-divergence areas are disproportionately located on the Z chromosome and overrepresented in gene networks relating to key traits separating the focal species, which are likely involved in reproductive barriers and/or species-specific adaptations. Of special interest are genes and functional groups known to affect body patterning, beak morphology, and the immune system, which are important features of diversification and fitness. We show that a combination of mosaic parental inheritance and novel divergence within the hybrid lineage has facilitated the origin and maintenance of an avian hybrid species.

• Wilson, Greg; Brian, Jennifer; Cranston, Karen; Kitzes, Justin; Nederbragt, Alexander Johan & Teal, Tracy K (2017). Good enough practices in scientific computing. PLoS Computational Biology. ISSN 1553-734X. 13(6). doi: 10.1371/journal.pcbi.1005510. Full text in Research Archive Show summary

  Computers are now essential in all branches of science, but most researchers are never taught the equivalent of basic lab skills for research computing. As a result, data can get lost, analyses can take much longer than necessary, and researchers are limited in how effectively they can work with software and data. Computing workflows need to follow the same practices as lab projects and notebooks, with organized data, documented steps, and the project structured for reproducibility, but researchers new to computing often don’t know where to start. This paper presents a set of good computing practices that every researcher can adopt, regardless of their current level of computational skill. These practices, which encompass data management, programming, collaborating with colleagues, organizing projects, tracking work, and writing manuscripts, are drawn from a wide variety of published sources from our daily lives and from our work with volunteer organizations that have delivered workshops to over 11,000 people since 2010.

• Khelik, Ksenia; Lagesen, Karin; Sandve, Geir Kjetil; Rognes, Torbjørn & Nederbragt, Alexander Johan (2017). NucDiff: in-depth characterization and annotation of differences between two sets of DNA sequences. BMC Bioinformatics. 18(1), p. 1–14. doi: 10.1186/s12859-017-1748-z. Full text in Research Archive Show summary

  Background Comparing sets of sequences is a situation frequently encountered in bioinformatics, examples being comparing an assembly to a reference genome, or two genomes to each other. The purpose of the comparison is usually to find where the two sets differ, e.g. to find where a subsequence is repeated or deleted, or where insertions have been introduced. Such comparisons can be done using whole-genome alignments. Several tools for making such alignments exist, but none of them 1) provides detailed information about the types and locations of all differences between the two sets of sequences, 2) enables visualisation of alignment results at different levels of detail, and 3) carefully takes genomic repeats into consideration. Results We here present NucDiff, a tool aimed at locating and categorizing differences between two sets of closely related DNA sequences. NucDiff is able to deal with very fragmented genomes, repeated sequences, and various local differences and structural rearrangements. NucDiff determines differences by a rigorous analysis of alignment results obtained by the NUCmer, delta-filter and show-snps programs in the MUMmer sequence alignment package. All differences found are categorized according to a carefully defined classification scheme covering all possible differences between two sequences. Information about the differences is made available as GFF3 files, thus enabling visualisation using genome browsers as well as usage of the results as a component in an analysis pipeline. NucDiff was tested with varying parameters for the alignment step and compared with existing alternatives, called QUAST and dnadiff. Conclusions We have developed a whole genome alignment difference classification scheme together with the program NucDiff for finding such differences. The proposed classification scheme is comprehensive and can be used by other tools. NucDiff performs comparably to QUAST and dnadiff but gives much more detailed results that can easily be visualized. NucDiff is freely available on https://github.com/uio-cels/NucDiff under the MPL license.

• Tørresen, Ole Kristian; Star, Bastiaan; Jentoft, Sissel; Reinar, William Brynildsen; Grove, Harald & Miller, Jason R. [Show all 16 contributors for this article] (2017). An improved genome assembly uncovers prolific tandem repeats in Atlantic cod. BMC Genomics. 18(1), p. 1–23. doi: 10.1186/s12864-016-3448-x. Full text in Research Archive Show summary

  Background The first Atlantic cod (Gadus morhua) genome assembly published in 2011 was one of the early genome assemblies exclusively based on high-throughput 454 pyrosequencing. Since then, rapid advances in sequencing technologies have led to a multitude of assemblies generated for complex genomes, although many of these are of a fragmented nature with a significant fraction of bases in gaps. The development of long-read sequencing and improved software now enable the generation of more contiguous genome assemblies. Results By combining data from Illumina, 454 and the longer PacBio sequencing technologies, as well as integrating the results of multiple assembly programs, we have created a substantially improved version of the Atlantic cod genome assembly. The sequence contiguity of this assembly is increased fifty-fold and the proportion of gap-bases has been reduced fifteen-fold. Compared to other vertebrates, the assembly contains an unusual high density of tandem repeats (TRs). Indeed, retrospective analyses reveal that gaps in the first genome assembly were largely associated with these TRs. We show that 21% of the TRs across the assembly, 19% in the promoter regions and 12% in the coding sequences are heterozygous in the sequenced individual. Conclusions The inclusion of PacBio reads combined with the use of multiple assembly programs drastically improved the Atlantic cod genome assembly by successfully resolving long TRs. The high frequency of heterozygous TRs within or in the vicinity of genes in the genome indicate a considerable standing genomic variation in Atlantic cod populations, which is likely of evolutionary importance.

• Malmstrøm, Martin; Matschiner, Michael; Tørresen, Ole Kristian; Star, Bastiaan; Snipen, Lars-Gustav & Hansen, Thomas F [Show all 13 contributors for this article] (2016). Evolution of the immune system influences speciation rates in teleost fishes. Nature Genetics. ISSN 1061-4036. 48(10), p. 1204–1210. doi: 10.1038/ng.3645. Full text in Research Archive Show summary

  Teleost fishes constitute the most species-rich vertebrate clade and exhibit extensive genetic and phenotypic variation, including diverse immune defense strategies. The genomic basis of a particularly aberrant strategy is exemplified by Atlantic cod, in which a loss of major histocompatibility complex (MHC) II functionality coincides with a marked expansion of MHC I genes. Through low-coverage genome sequencing (9–39×), assembly and comparative analyses for 66 teleost species, we show here that MHC II is missing in the entire Gadiformes lineage and thus was lost once in their common ancestor. In contrast, we find that MHC I gene expansions have occurred multiple times, both inside and outside this clade. Moreover, we identify an association between high MHC I copy number and elevated speciation rates using trait-dependent diversification models. Our results extend current understanding of the plasticity of the adaptive immune system and suggest an important role for immune-related genes in animal diversification.

• Star, Bastiaan; Tørresen, Ole Kristian; Nederbragt, Alexander Johan; Jakobsen, Kjetill Sigurd; Pampoulie, Christophe & Jentoft, Sissel (2016). Genomic characterization of the Atlantic cod sex-locus. Scientific Reports. 6, p. 1–9. doi: 10.1038/srep31235. Full text in Research Archive Show summary

  A variety of sex determination mechanisms can be observed in evolutionary divergent teleosts. Sex determination is genetic in Atlantic cod (Gadus morhua), however the genomic location or size of its sex-locus is unknown. Here, we characterize the sex-locus of Atlantic cod using whole genome sequence (WGS) data of 227 wild-caught specimens. Analyzing more than 55 million polymorphic loci, we identify 166 loci that are associated with sex. These loci are located in six distinct regions on fve diferent linkage groups (LG) in the genome. The largest of these regions, an approximately 55Kb region on LG11, contains the majority of genotypes that segregate closely according to a XX-XY system. Genotypes in this region can be used genetically determine sex, whereas those in the other regions are inconsistently sex-linked. The identifed region on LG11 and its surrounding genes have no clear sequence homology with genes or regulatory elements associated with sex-determination or diferentiation in other species. The functionality of this sex-locus therefore remains unknown. The WGS strategy used here proved adequate for detecting the small regions associated with sex in this species. Our results highlight the evolutionary fexibility in genomic architecture underlying teleost sexdetermination and allow practical applications to genetically sex Atlantic cod.

• Frank, Jeremy A.; Pan, Yao; Tooming-Klunderud, Ave; Eijsink, Vincent; McHardy, Alice C & Nederbragt, Alexander Johan [Show all 7 contributors for this article] (2016). Improved metagenome assemblies and taxonomic binning using long-read circular consensus sequence data. Scientific Reports. 6. doi: 10.1038/srep25373. Full text in Research Archive Show summary

  DNA assembly is a core methodological step in metagenomic pipelines used to study the structure and function within microbial communities. Here we investigate the utility of Pacific Biosciences long and high accuracy circular consensus sequencing (CCS) reads for metagenomic projects. We compared the application and performance of both PacBio CCS and Illumina HiSeq data with assembly and taxonomic binning algorithms using metagenomic samples representing a complex microbial community. Eight SMRT cells produced approximately 94 Mb of CCS reads from a biogas reactor microbiome sample that averaged 1319 nt in length and 99.7% accuracy. CCS data assembly generated a comparative number of large contigs greater than 1 kb, to those assembled from a ~190x larger HiSeq dataset (~18 Gb) produced from the same sample (i.e approximately 62% of total contigs). Hybrid assemblies using PacBio CCS and HiSeq contigs produced improvements in assembly statistics, including an increase in the average contig length and number of large contigs. The incorporation of CCS data produced significant enhancements in taxonomic binning and genome reconstruction of two dominant phylotypes, which assembled and binned poorly using HiSeq data alone. Collectively these results illustrate the value of PacBio CCS reads in certain metagenomics applications.

• Tørresen, Ole Kristian; Rise, Matthew L.; Jin, Xingkun; Star, Bastiaan; MacKenzie, Simon & Jakobsen, Kjetill Sigurd [Show all 8 contributors for this article] (2016). An improved version of the Atlantic cod genome and advancements in functional genomics: implications for the future of cod farming. In MacKenzie, Simon & Jentoft, Sissel (Ed.), Genomics in Aquaculture. Elsevier. ISSN 9780128014189. p. 45–72. doi: 10.1016/B978-0-12-801418-9.00003-2. Full text in Research Archive
• Tørresen, Ole Kristian; Star, Bastiaan; Jentoft, Sissel; Jakobsen, Kjetill Sigurd & Nederbragt, Alexander Johan (2016). The new era of genome sequencing using high-throughput sequencing technology: Generation of the first version of the Atlantic cod genome. In MacKenzie, Simon & Jentoft, Sissel (Ed.), Genomics in Aquaculture. Elsevier. ISSN 9780128014189. p. 1–20. doi: 10.1016/B978-0-12-801418-9.00001-9. Full text in Research Archive
• Solbakken, Monica Hongrø; Tørresen, Ole Kristian; Nederbragt, Alexander Johan; Seppola, Marit; Gregers, Tone Fredsvik & Jakobsen, Kjetill Sigurd [Show all 7 contributors for this article] (2016). Evolutionary redesign of the Atlantic cod (Gadus morhua L.) Toll-like receptor repertoire by gene losses and expansions. Scientific Reports. 6. doi: 10.1038/srep25211. Full text in Research Archive Show summary

  Genome sequencing of the teleost Atlantic cod demonstrated loss of the Major Histocompatibility Complex (MHC) class II, an extreme gene expansion of MHC class I and gene expansions and losses in the innate pattern recognition receptor (PRR) family of Toll-like receptors (TLR). In a comparative genomic setting, using an improved version of the genome, we characterize PRRs in Atlantic cod with emphasis on TLRs demonstrating the loss of TLR1/6, TLR2 and TLR5 and expansion of TLR7, TLR8, TLR9, TLR22 and TLR25. We find that Atlantic cod TLR expansions are strongly influenced by diversifying selection likely to increase the detectable ligand repertoire through neo- and subfunctionalization. Using RNAseq we find that Atlantic cod TLRs display likely tissue or developmental stage-specific expression patterns. In a broader perspective, a comprehensive vertebrate TLR phylogeny reveals that the Atlantic cod TLR repertoire is extreme with regards to losses and expansions compared to other teleosts. In addition we identify a substantial shift in TLR repertoires following the evolutionary transition from an aquatic vertebrate (fish) to a terrestrial (tetrapod) life style. Collectively, our findings provide new insight into the function and evolution of TLRs in Atlantic cod as well as the evolutionary history of vertebrate innate immunity.

• Lien, Sigbjørn; Koop, Ben F; Sandve, Simen Rød; Miller, Jason R.; Kent, Matthew Peter & Nome, Torfinn [Show all 45 contributors for this article] (2016). The Atlantic salmon genome provides insights into rediploidization. Nature. ISSN 0028-0836. 533(7602), p. 200–205. doi: 10.1038/nature17164. Full text in Research Archive Show summary

  The whole-genome duplication 80 million years ago of the common ancestor of salmonids (salmonid-specific fourth vertebrate whole-genome duplication, Ss4R) provides unique opportunities to learn about the evolutionary fate of a duplicated vertebrate genome in 70 extant lineages. Here we present a high-quality genome assembly for Atlantic salmon (Salmo salar), and show that large genomic reorganizations, coinciding with bursts of transposon-mediated repeat expansions, were crucial for the post-Ss4R rediploidization process. Comparisons of duplicate gene expression patterns across a wide range of tissues with orthologous genes from a pre-Ss4R outgroup unexpectedly demonstrate far more instances of neofunctionalization than subfunctionalization. Surprisingly, we find that genes that were retained as duplicates after the teleost-specific whole-genome duplication 320 million years ago were not more likely to be retained after the Ss4R, and that the duplicate retention was not influenced to a great extent by the nature of the predicted protein interactions of the gene products. Finally, we demonstrate that the Atlantic salmon assembly can serve as a reference sequence for the study of other salmonids for a range of purposes.

• Crusoe, Michael R.; Alameldin, Hussien F.; Awad, Sherine; Boucher, Elmar; Caldwell, Adam & Cartwright, Reed [Show all 61 contributors for this article] (2015). The khmer software package: enabling efficient nucleotide sequence analysis. F1000 Research. p. 1–12. doi: 10.12688/f1000research.6924.1. Full text in Research Archive
• Siddiqui, Huma; Lagesen, Karin; Nederbragt, Alexander Johan; Eri, Lars Magne; Jeansson, Stig & Jakobsen, Kjetill Sigurd (2014). Pathogens in Urine from a Female Patient with Overactive Bladder Syndrome Detected by Culture-Independent High Throughput Sequencing: A Case Report. Open Microbiology Journal. 8, p. 148–153. doi: 10.2174/1874285801408010148. Full text in Research Archive
• Hermansen, Jo Skeie; Haas, Fredrik; Trier, Cassandra Nicole; Bailey, Richard Ian; Nederbragt, Alexander Johan & Marzal, Alfonso [Show all 7 contributors for this article] (2014). Hybrid speciation through sorting of parental incompatibilities in Italian sparrows. Molecular Ecology. ISSN 0962-1083. 23(23), p. 5831–5842. doi: 10.1111/mec.12910. Full text in Research Archive
• Brembu, Tore; Winge, Per; Tooming-Klunderud, Ave; Nederbragt, Alexander Johan; Jakobsen, Kjetill Sigurd & Bones, Atle M. (2014). The chloroplast genome of the diatom Seminavis robusta: New features introduced through multiple mechanisms of horizontal gene transfer. Marine Genomics. ISSN 1874-7787. 16(1), p. 17–27. doi: 10.1016/j.margen.2013.12.002. Full text in Research Archive
• Star, Bastiaan; Nederbragt, Alexander Johan; Hansen, Marianne Helén Selander; Skage, Morten; Gilfillan, Gregor Duncan & Bradbury, Ian R. [Show all 10 contributors for this article] (2014). Palindromic sequence artifacts generated during next generation sequencing library preparation from historic and ancient DNA. PLOS ONE. 9(3). doi: 10.1371/journal.pone.0089676. Full text in Research Archive Show summary

  Degradation-specific processes and variation in laboratory protocols can bias the DNA sequence composition from samples of ancient or historic origin. Here, we identify a novel artifact in sequences from historic samples of Atlantic cod (Gadus morhua), which forms interrupted palindromes consisting of reverse complementary sequence at the 5′ and 3′-ends of sequencing reads. The palindromic sequences themselves have specific properties – the bases at the 5′-end align well to the reference genome, whereas extensive misalignments exists among the bases at the terminal 3′-end. The terminal 3′ bases are artificial extensions likely caused by the occurrence of hairpin loops in single stranded DNA (ssDNA), which can be ligated and amplified in particular library creation protocols. We propose that such hairpin loops allow the inclusion of erroneous nucleotides, specifically at the 3′-end of DNA strands, with the 5′-end of the same strand providing the template. We also find these palindromes in previously published ancient DNA (aDNA) datasets, albeit at varying and substantially lower frequencies. This artifact can negatively affect the yield of endogenous DNA in these types of samples and introduces sequence bias.

• Tooming-Klunderud, Ave; Sogge, Hanne; Rounge, Trine Ballestad; Nederbragt, Alexander Johan; Lagesen, Karin & Glöckner, Gernot [Show all 9 contributors for this article] (2013). From Green to Red: Horizontal Gene Transfer of the Phycoerythrin Gene Cluster between Planktothrix Strains. Applied and Environmental Microbiology. ISSN 0099-2240. 79(21), p. 6803–6812. doi: 10.1128/AEM.01455-13. Full text in Research Archive Show summary

  Horizontal gene transfer is common in cyanobacteria, and transfer of large gene clusters may lead to acquisition of new functions and conceivably niche adaption. In the present study, we demonstrate that horizontal gene transfer between closely related Planktothrix strains can explain the production of the same oligopeptide isoforms by strains of different colors. Comparison of the genomes of eight Planktothrix strains revealed that strains producing the same oligopeptide isoforms are closely related, regardless of color. We have investigated genes involved in the synthesis of the photosynthetic pigments phycocyanin and phycoerythrin, which are responsible for green and red appearance, respectively. Sequence comparisons suggest the transfer of a functional phycoerythrin gene cluster generating a red phenotype in a strain that is otherwise more closely related to green strains. Our data show that the insertion of a DNA fragment containing the 19.7-kb phycoerythrin gene cluster has been facilitated by homologous recombination, also replacing a region of the phycocyanin operon. These findings demonstrate that large DNA fragments spanning entire functional gene clusters can be effectively transferred between closely related cyanobacterial strains and result in a changed phenotype. Further, the results shed new light on the discussion of the role of horizontal gene transfer in the sporadic distribution of large gene clusters in cyanobacteria, as well as the appearance of red and green strains.

• Siddiqui, Huma; Lagesen, Karin; Nederbragt, Alexander Johan; Jeansson, Stig & Jakobsen, Kjetill Sigurd (2012). Alterations of microbiota in urine from women with interstitial cystitis. BMC Microbiology. 12(205). doi: 10.1186/1471-2180-12-205. Full text in Research Archive Show summary

  Background Interstitial Cystitis (IC) is a chronic inflammatory condition of the bladder with unknown etiology. The aim of this study was to characterize the microbial community present in the urine from IC female patients by 454 high throughput sequencing of the 16S variable regions V1V2 and V6. The taxonomical composition, richness and diversity of the IC microbiota were determined and compared to the microbial profile of asymptomatic healthy female (HF) urine. Results The composition and distribution of bacterial sequences differed between the urine microbiota of IC patients and HFs. Reduced sequence richness and diversity were found in IC patient urine, and a significant difference in the community structure of IC urine in relation to HF urine was observed. More than 90% of the IC sequence reads were identified as belonging to the bacterial genus Lactobacillus, a marked increase compared to 60% in HF urine. Conclusion The 16S rDNA sequence data demonstrates a shift in the composition of the bacterial community in IC urine. The reduced microbial diversity and richness is accompanied by a higher abundance of the bacterial genus Lactobacillus, compared to HF urine. This study demonstrates that high throughput sequencing analysis of urine microbiota in IC patients is a powerful tool towards a better understanding of this enigmatic disease.

• Logares, Ramiro; Haverkamp, Thomas Hendricus Augustus; Kumar, Surendra; Lanzén, Anders; Nederbragt, Alexander Johan & Quince, Christopher [Show all 7 contributors for this article] (2012). Environmental microbiology through the lens of high-throughput DNA sequencing: Synopsis of current platforms and bioinformatics approaches. Journal of Microbiological Methods. ISSN 0167-7012. 91(1), p. 106–113. doi: 10.1016/j.mimet.2012.07.017. Full text in Research Archive
• Espelund, Mari; Minge, Marianne Aastebøl; Gabrielsen, Tove M; Nederbragt, Alexander Johan; Shalchian-Tabrizi, Kamran & Otis, Christian [Show all 9 contributors for this article] (2012). Genome Fragmentation Is Not Confined to the Peridinin Plastid in Dinoflagellates. PLOS ONE. 7(6). doi: 10.1371/journal.pone.0038809. Full text in Research Archive Show summary

  When plastids are transferred between eukaryote lineages through series of endosymbiosis, their environment changes dramatically. Comparison of dinoflagellate plastids that originated from different algal groups has revealed convergent evolution, suggesting that the host environment mainly influences the evolution of the newly acquired organelle. Recently the genome from the anomalously pigmented dinoflagellate Karlodinium veneficum plastid was uncovered as a conventional chromosome. To determine if this haptophyte-derived plastid contains additional chromosomal fragments that resemble the mini-circles of the peridin-containing plastids, we have investigated its genome by in-depth sequencing using 454 pyrosequencing technology, PCR and clone library analysis. Sequence analyses show several genes with significantly higher copy numbers than present in the chromosome. These genes are most likely extrachromosomal fragments, and the ones with highest copy numbers include genes encoding the chaperone DnaK(Hsp70), the rubisco large subunit (rbcL), and two tRNAs (trnE and trnM). In addition, some photosystem genes such as psaB, psaA, psbB and psbD are overrepresented. Most of the dnaK and rbcL sequences are found as shortened or fragmented gene sequences, typically missing the 3′-terminal portion. Both dnaK and rbcL are associated with a common sequence element consisting of about 120 bp of highly conserved AT-rich sequence followed by a trnE gene, possibly serving as a control region. Decatenation assays and Southern blot analysis indicate that the extrachromosomal plastid sequences do not have the same organization or lengths as the minicircles of the peridinin dinoflagellates. The fragmentation of the haptophyte-derived plastid genome K. veneficum suggests that it is likely a sign of a host-driven process shaping the plastid genomes of dinoflagellates.

• Gabrielsen, Tove M; Minge, Marianne Aastebøl; Espelund, Mari; Tooming-Klunderud, Ave; Patil, Viswanath & Nederbragt, Alexander Johan [Show all 11 contributors for this article] (2011). Genome Evolution of a Tertiary Dinoflagellate Plastid. PLOS ONE. 6(4), p. e19132–e19132. doi: 10.1371/journal.pone.0019132. Full text in Research Archive
• Siddiqui, Huma; Nederbragt, Alexander Johan; Lagesen, Karin; Jeansson, Stig & Jakobsen, Kjetill Sigurd (2011). Assessing diversity of the female urine microbiota by high throughput sequencing of 16S rDNA amplicons. BMC Microbiology. 11. doi: 10.1186/1471-2180-11-244. Full text in Research Archive Show summary

  Background Urine within the urinary tract is commonly regarded as "sterile" in cultivation terms. Here, we present a comprehensive in-depth study of bacterial 16S rDNA sequences associated with urine from healthy females by means of culture-independent high-throughput sequencing techniques. Results Sequencing of the V1V2 and V6 regions of the 16S ribosomal RNA gene using the 454 GS FLX system was performed to characterize the possible bacterial composition in 8 culture-negative (<100,000 CFU/ml) healthy female urine specimens. Sequences were compared to 16S rRNA databases and showed significant diversity, with the predominant genera detected being Lactobacillus, Prevotella and Gardnerella. The bacterial profiles in the female urine samples studied were complex; considerable variation between individuals was observed and a common microbial signature was not evident. Notably, a significant amount of sequences belonging to bacteria with a known pathogenic potential was observed. The number of operational taxonomic units (OTUs) for individual samples varied substantially and was in the range of 20 - 500. Conclusions Normal female urine displays a noticeable and variable bacterial 16S rDNA sequence richness, which includes fastidious and anaerobic bacteria previously shown to be associated with female urogenital pathology.

• Brede, Dag Anders; Snipen, Lars-Gustav; Ussery, David Wayne; Nederbragt, Alexander Johan & Nes, Ingolf (2011). Complete Genome Sequence of the Commensal Enterococcus faecalis 62, Isolated from a Healthy Norwegian Infant. Journal of Bacteriology. ISSN 0021-9193. 193(9), p. 2377–2378. doi: 10.1128/JB.00183-11. Full text in Research Archive
• Star, Bastiaan; Nederbragt, Alexander Johan; Jentoft, Sissel; Grimholt, Unni; Malmstrøm, Martin & Gregers, Tone Fredsvik [Show all 42 contributors for this article] (2011). The genome sequence of Atlantic cod reveals a unique immune system. Nature. ISSN 0028-0836. 477(7363), p. 207–210. doi: 10.1038/nature10342. Full text in Research Archive Show summary

  Atlantic cod (Gadus morhua) is a large, cold-adapted teleost that sustains long-standing commercial fisheries and incipient aquaculture. Here we present the genome sequence of Atlantic cod, showing evidence for complex thermal adaptations in its haemoglobin gene cluster and an unusual immune architecture compared to other sequenced vertebrates. The genome assembly was obtained exclusively by 454 sequencing of shotgun and paired-end libraries, and automated annotation identified 22,154 genes. The major histocompatibility complex (MHC) II is a conserved feature of the adaptive immune system of jawed vertebrates, but we show that Atlantic cod has lost the genes for MHC II, CD4 and invariant chain (Ii) that are essential for the function of this pathway. Nevertheless, Atlantic cod is not exceptionally susceptible to disease under natural conditions5. We find a highly expanded number of MHC I genes and a unique composition of its Toll-like receptor (TLR) families. This indicates how the Atlantic cod immune system has evolved compensatory mechanisms in both adaptive and innate immunity in the absence of MHC II. These observations affect fundamental assumptions about the evolution of the adaptive immune system and its components in vertebrates.

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• Nederbragt, Lex (2025). GPT UiO som læringsassistent i BIOS1101. doi: https:/www.uio.no/link/arrangementer/2025/Utdanningskonferansen2025.html. Full text in Research Archive
• Gregers, Tone Fredsvik; Langford, Malcolm; Maasø, Arnt; Brevik, Lisbeth M.; Mjaaland, Marius & Mirmotahari, Omid [Show all 25 contributors for this article] (2025). Utdanningskvalitet: Hva kan vi forvente av UiOs framtidige rektorteam? Full text in Research Archive
• Nederbragt, Lex (2023). Cognitive Load: what is it and how can we take it in consideration when teaching? Full text in Research Archive
• Nederbragt, Lex (2022). Carpentry@UiO: Workshops for basic skills in programming and datamanagement at The University of Oslo (UiO). Full text in Research Archive
• Nederbragt, Lex (2021). Using Jupyter for teaching programming to bachelor students in Bioscience. Full text in Research Archive
• Eliassen, June Edvarda; Bøe, Maria Vetleseter; Nederbragt, Lex & Gregers, Tone Fredsvik (2021). Motivasjon for beregningsorientert biologi og sammenhengen med matematikk R2 fra videregående opplæring. Full text in Research Archive
• Nederbragt, Alexander Johan; Harris, Rayna Michelle; Hill, Alison Presmanes & Wilson, Greg (2020). Ten quick tips for teaching with participatory live coding. PLoS Computational Biology. ISSN 1553-734X. 16(9), p. 1–7. doi: 10.1371/journal.pcbi.1008090. Full text in Research Archive
• Fyhn, Marianne; Malthe-Sørenssen, Anders; Mørken, Knut Martin; Nederbragt, Alexander Johan; Odden, Tor Ole & Sundnes, Joakim (2019). Beregningsorientering og utdanningsutvikling. Full text in Research Archive
• Nederbragt, Alexander Johan (2019). Learning from the Carpentries. Full text in Research Archive
• Nederbragt, Alexander Johan (2018). Programmering og modellering i biovitenskapsutdanning. Full text in Research Archive
• Reinar, William Brynildsen; Tørresen, Ole K.; Matschiner, Michael; Jentoft, Sissel; Nederbragt, Alexander Johan & Jakobsen, Kjetill Sigurd (2018). The impact of repetitive DNA on speciation rates in teleost fish. Full text in Research Archive
• Nederbragt, Alexander Johan (2017). Software Carpentry og Data Carpentry: opplæring i bruk og deling av forskningsdata – for forskere, av forskere, ved UiO. Full text in Research Archive
• Nederbragt, Alexander Johan (2017). Teaching Researchers Basic Skills for Computational Research: the Software Carpentry Model. Full text in Research Archive
• Nederbragt, Alexander Johan (2017). How I got infected by fish genomics - and how you can too. Full text in Research Archive
• Sandve, Simen Rød; Hvidsten, Torgeir Rhoden; Lien, Sigbjørn; Rori, Rohlfs; Jakobsen, Kjetill Sigurd & Nome, Torfinn [Show all 9 contributors for this article] (2017). Evolution after whole genome duplication - insights from the salmonids. Full text in Research Archive
• Tennøe, Simen; Mobarhan, Milad; Dragly, Svenn-Arne; Solbrå, Andreas Våvang & Nederbragt, Alexander Johan (2017). Teaching modelling to first-year biology students. Full text in Research Archive Show summary

  The field of biology relies heavily on computations. This is not well reflected in education and the current undergraduate curriculum has little computational content. This results in a discontinuity between the education received by the students and the problems they face after graduation. The end result is that the students are not equipped to meet the requirements of modern research nor the tasks awaiting them in the industry. To remedy this problem, a new course, BIOS 1100 - Introduction to Modelling in Biology, will be held for the first time at the University of Oslo in fall 2017. Currently, no available book combines biology and programming at an introductory level in a satisfactory way. Most textbooks teach both topics separately or expect the reader to know either biology or programming from before. We have therefore written our own textbook to be used as curriculum in this course. This book aims to teach programming and modelling to first year biology students through examples from biology. The book is based on a philosophy of just-in-time teaching where the programming concepts are introduced just when they are needed to solve the problem in hand. This puts the programming content in an unusual order in comparison to the traditional computer science curriculum while keeping the biology students motivated by the problems they solve. The examples are mainly from the three branches of biology: population dynamics, bioinformatics and evolution. The purpose is to give biology students a practical understanding of programming and mathematical models. This will enable the understanding of mathematical models and encourage critical thinking. Programming allows much more realistic and inspiring problems to be addressed, enabling students to work on current research topics early on. The textbook is written using DocOnce (created by Hans Petter Langtangen), which enables us to compile the book to both LaTeX/PDF, HTML and Jupyter Notebooks.

• Nederbragt, Alexander Johan (2016). The new Atlantic cod reference genome. Full text in Research Archive
• Nederbragt, Alexander Johan & Lagesen, Karin (2016). The Carpentry effort at the University of Oslo. Full text in Research Archive
• Nederbragt, Alexander Johan (2016). SMRTwishes for SMRTsoftware for SMRTreads - a user’s perspective. Full text in Research Archive
• Nederbragt, Alexander Johan (2016). Doing bioinformatics: a user’s perspective. Full text in Research Archive
• Nederbragt, Alexander Johan (2016). Genomic variation detection in Atlantic cod using long reads. Full text in Research Archive
• Eide, Marta; Puntervoll, Pål; Lille-Langøy, Roger; Goldstone, Jared V.; Tørresen, Ole Kristian & Nederbragt, Alexander Johan [Show all 11 contributors for this article] (2016). Chemical warfare in the marine environment: genomic survey of the Atlantic cod (Gadus morhua) defensome reveals the absence of an important xenosensor. Full text in Research Archive
• Nederbragt, Alexander Johan (2015). Local, central or cloud Why we chose to build our e-infrastructure for sequence analysis embedded in the university of Oslo HPC cluster. Full text in Research Archive
• Nederbragt, Alexander Johan (2015). Active learning strategies for bioinformatics teaching. Full text in Research Archive
• Nederbragt, Alexander Johan (2015). A New, High Quality Reference Genome Assembly For Atlantic Cod. Full text in Research Archive
• Star, Bastiaan; Jentoft, Sissel; Matschiner, Michael; Nederbragt, Alexander Johan; Kjesbu, Olav Sigurd & Berg, Paul Ragnar [Show all 12 contributors for this article] (2015). Does historic DNA provide genomic evidence for recent selection in Atlantic cod? Full text in Research Archive
• Nederbragt, Alexander Johan (2015). Bioinformatics breakout : Recent experiences from Oslo. Full text in Research Archive
• Tørresen, Ole Kristian; Jentoft, Sissel; Star, Bastiaan; Sandve, Geir Kjetil F.; Skage, Morten & Hansen, Marianne Helén Selander [Show all 9 contributors for this article] (2014). A new, high quality reference genome assembly for Atlantic cod. Full text in Research Archive
• Tørresen, Ole Kristian; Walenz, Brian; Grove, Harald; Lien, Sigbjørn; Knight, James & Star, Bastiaan [Show all 15 contributors for this article] (2014). A new, high quality reference genome assembly for Atlantic cod. Full text in Research Archive
• Matschiner, Michael; Star, Bastiaan; Berg, Paul Ragnar; Tørresen, Ole Kristian; Nederbragt, Alexander Johan & Hansen, Marianne Helén Selander [Show all 11 contributors for this article] (2014). Population differentiation and local adaptation in Atlantic cod. Full text in Research Archive
• Nederbragt, Alexander Johan (2014). The why and how of long reads for de novo genome assembly. Full text in Research Archive
• Brynildsen, William; Tørresen, Ole Kristian; Jakobsen, Kjetill Sigurd & Nederbragt, Alexander Johan (2014). Genomic sequence repeats in fish genomes. Full text in Research Archive
• Nederbragt, Alexander Johan (2014). The why and how of long reads for de novo genome assembly. Full text in Research Archive
• Nederbragt, Alexander Johan (2014). Mix and match: using multiple sequencing technologies and assemblers for the new Atlantic cod genome. Full text in Research Archive
• Nederbragt, Alexander Johan (2014). Coding & Best Practice in Programming: Why it matters so much in the NGS era. Full text in Research Archive
• Nederbragt, Alexander Johan (2014). Assembly – before and after. Full text in Research Archive
• Nederbragt, Alexander Johan; Walenz, Brian; Tørresen, Ole Kristian; Jentoft, Sissel; Jakobsen, Kjetill Sigurd & Miller, Jason Rafe (2014). Towards correction-free assembly of raw PacBio reads. Full text in Research Archive
• Nederbragt, Alexander Johan (2013). Repeat after me: Is our research reproducible (enough)? Full text in Research Archive
• Nederbragt, Alexander Johan (2013). The IPython Notebook: an introduction, and hands-on/live demo. Full text in Research Archive
• Tørresen, Ole Kristian; Nederbragt, Alexander Johan; Miller, Jason Rafe; Walenz, Brian; Jentoft, Sissel & Jakobsen, Kjetill Sigurd (2013). Improving the Atlantic cod genome using long-read PacBio in combination with 454 and Illumina sequencing data. Full text in Research Archive
• Nederbragt, Alexander Johan (2013). Using PacBio Reads to Improve and Validate the Assembly of the Complex Atlantic Cod Genome. Full text in Research Archive
• Nederbragt, Alexander Johan (2013). High Throughput Sequencing technologies at the Norwegian Sequencing Centre with a focus on genome assembly. Full text in Research Archive
• Nederbragt, Alexander Johan (2013). Lessons learned from assembling the Atlantic cod genome. Full text in Research Archive
• Loman, N.; Hadfield, James & Nederbragt, Alexander Johan (2013). Seqbench: Open-source benchmarking of sequence platforms and software. Full text in Research Archive
• Nederbragt, Alexander Johan (2013). High Throughput Sequencing technologies. Full text in Research Archive
• Nederbragt, Alexander Johan (2013). Improving and validating the Atlantic Cod genome assembly using error-corrected as well as raw PacBio reads. Full text in Research Archive
• Nederbragt, Alexander Johan (2013). The IPython Notebook: an introduction, and hands-on/live demo. Full text in Research Archive
• Nederbragt, Alexander Johan; Tørresen, Ole Kristian; Skage, Morten; Tooming-Klunderud, Ave; Hansen, Marianne Helén Selander & Jentoft, Sissel [Show all 9 contributors for this article] (2012). The long jump: Long distance mate pairs and long PacBio reads for the Salmon Genome Project. Full text in Research Archive
• Nederbragt, Alexander Johan (2012). How and why I use blogging and twitter for science. Full text in Research Archive
• Nederbragt, Alexander Johan (2012). The bioinformatics of sequencing and assembling genomes - with a focus on the Atlantic cod and salmon genome projects. Full text in Research Archive
• Nederbragt, Alexander Johan (2012). Experiences with Combining PacBio with Short Read Technology for Improved de novo Assembly of Complex Genomes. Full text in Research Archive
• Nederbragt, Alexander Johan (2012). High-throughput sequencing og behovet for tungregneressurser. Full text in Research Archive
• Nederbragt, Alexander Johan (2012). New High Throughput Sequencing technologies at the Norwegian Sequencing Centre - and beyond. Full text in Research Archive
• Nederbragt, Alexander Johan (2012). The best of both worlds - Combining PacBio with short read technology for improved de novo genome assembly. Full text in Research Archive
• Nederbragt, Alexander Johan (2012). New High Throughput Sequencing technologies at the Norwegian Sequencing Centre - and beyond. Full text in Research Archive
• Nederbragt, Alexander Johan (2012). Experiences with Combining PacBio with Short Read Technology for Improved de novo Assembly of Complex Genomes. Full text in Research Archive
• Nederbragt, Alexander Johan (2012). A different kettle of fish entirely: bioinformatic challenges and solutions for whole de novo genome assembly of Atlantic cod and Atlantic salmon. Full text in Research Archive
• Tørresen, Ole Kristian; Nederbragt, Alexander Johan; Lagesen, Karin; Khelik, Ksenia; Rognes, Torbjørn & Jentoft, Sissel [Show all 7 contributors for this article] (2012). Improving the cod genome with the use of multi-platform sequencing data. Full text in Research Archive
• Nederbragt, Alexander Johan; Tørresen, Ole Kristian; Khelik, Ksenia; Lagesen, Karin; Rounge, Trine Ballestad & Star, Bastiaan [Show all 13 contributors for this article] (2012). Challenges and Opportunities for Improving the Atlantic Cod Genome Assembly and Annotation. Full text in Research Archive
• Rounge, Trine Ballestad & Nederbragt, Alexander Johan (2011). The Atlantic Cod Genome Project. Full text in Research Archive
• Nederbragt, Alexander Johan; Lagesen, Karin & Malmstrøm, Martin (2011). Bioinformatic analysis of genomic data. Full text in Research Archive
• Nederbragt, Alexander Johan (2011). How to sequence a large eukaryotic genome and how we sequenced the cod genom. Full text in Research Archive
• Nederbragt, Alexander Johan (2011). Next generation sequencing: research opportunities and bioinformatic challenges. Full text in Research Archive
• Løvoll, Marie Therese; Wiik-Nielsen, Jannicke; Grove, Søren; Wiik-Nielsen, Christer R.; Kristoffersen, Anja Bråthen & Jung, J. [Show all 11 contributors for this article] (2011). Totivirus og reovirus i laks med kardiomyopatisyndrom (CMS). Full text in Research Archive

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