LiceBase blogs

Downtime announcement and service retirement note

Michael Dondrup — Thu, 21 Nov 2024 09:49:05 +0000

LiceBase will be retired starting 5.1.2025

LiceBase has been in continous operation since 2016. Unfortunetely, I have to retire LiceBase on January 5. 2025 due to technical and security reasons.
On that date, the current service will be retired and the URL licebase.org will become inaccessible. See below for a more detailed explanation.
I am working on the new version likely called LiceBase2 to be available at the same URL which is going to replace LiceBase and will be released in early 2025. However, a downtime will be inevitable.
Unfortunately, I am unable to estimate the exact duration of the downtime at the current point in time but I expect it to last at least two months.
This decision and the chain of coming events regarding the service is final. On behalf of the Sea Lice Research Centre and ELIXIR Norway we apologize for any inconvenience caused by this.

Explanation of reasons

LiceBase is based on the content management framework Drupal 7 and the extension module Tripal for managing and displaying genomics data. After several prolongations, Drupal 7 will reach its End Of Life (EOL) on January 5., 2025. After this date, there will be now more updates for the Drupal 7 core, and therefore operating a web-site securely based on the current system would be impossible. Unfortunately, the Tripal project has not delivered a stable release version and is unlikely to do so in time for the EOL date of Drupal 7. The current alpha version of Tripal 4 is too unstable and is lacking some essential functionality, such as searching for genes and displaying gene sequences, to provide a viable update path for us at the moment. We are still working on a preliminary solution based on Tripal 4 but there is likely going to be a significant loss of functionality on the new site at first.
All experimental annotation and meta-data will remain safely stored in the database system of LiceBase but might not be accessible immediately in a first-release candidate of LiceBase2.

Many sites operating Drupal/Tripal are facing similar prospects. LiceBase has joined the GenoRing consortium and is collaborating with ELIXIR and ENA to secure funding and continuous operation of important organism databases.

Moving forward with LiceBase 2

With the implementation of the next version of LiceBase, we will move to a new cloud-based hosting solution for our services. This should increase the overall performance and reliability of the service.
In connection with the update we are planning to make the following changes:

We will add additional sea lice genomes that have become available recently
An update of the Atlantic salmon louse assembly and annotation is likely to be hosted on LiceBase first
We are likely going to cease Feide authentication for a more general OpenID-based authentication. Most users will not need to register for an account to use the site.

Atlantic salmon louse genome removed from Ensembl Metazoa

Michael Dondrup — Thu, 18 Jan 2024 09:36:44 +0000

The Atlantic salmon louse genome assembly (LSalAtl2s) has unfortunately been retired from Ensembl Metazoa Release 57. We think this is a slightly unfortunate decision because 1. Many are still using the LSalAtl2s assembly and the genes, as it has been around for over ten year 2. The Atlantic and Pacific versions of the genome belong to distinct sub-species.

Anyway, the genome and annotation are still available via the archived version of ENSEMBL Metazoa Release 56 and of course through LiceBase. All Cross-reference links have been updated.

Sequencing technology, especially for long-read sequencing has massively advanced since the first assembly came out. Today, with a fraction of the funding used for LSalAtl2s we would likely be able to generate a high-quality haplotype-resolved (precisely capturing the states of each chromosome pair) telomere-to-telomere assembly.

The time may be right for sequencing the Atlantic salmon louse genome again. If you are interested in creating a new genome sequence either by contributing time or funding or if you need bioinformatics support for your analyses, please contact us.

Performance problems [SOLVED]

Michael Dondrup — Wed, 18 May 2022 11:16:21 +0000

LiceBase has experienced some serious performance issues lately. I think I have fixed the problem which was related to Drupal's database tables for now.

LiceBase@SeaLice2022

Michael Dondrup — Tue, 03 May 2022 15:00:02 +0000

LiceBase folks will be present at Sea Lice Conference International 2022 in Tórshavn in the Faroe Islands. We are looking forward to four days of exciting presentations on sea Lice Biology, genetics and genomics, medicinal and non-medicinal treatments, modeling, and many more. The Sea Lice Conference is an excellent venue to meet a vibrant research community and engage in discussion with top of the field researchers.
Please feel free to engage with us in discussions of sea lice genomics and target discovery. The conference program reflects the growing importance of computational methods, databases, and modeling in modern sea lice research.

The Earth BioGenome Project Norway is Hiring

Michael Dondrup — Fri, 07 Jan 2022 14:19:49 +0000

At the Department of Informatics, University of Bergen, Norway, there is a vacancy for a postdoctoral research fellow position within Informatics – Bioinformatics.

The position is for a fixed term of 4 years and is connected to the project Earth Biogenome Project Norge (EBP-Nor, A Norwegian BioGenome initiative: the initial Launch phase), financed by the Research Council of Norway.

About the project/work tasks:
The Earth BioGenome Project (EBP) is a global non-profit initiative with the aim to catalog the genomes of the entirety of all of Earth's 1.5 million eukaryotic species over a period of ten years. The Norwegian national network node of EBP, EBPNor, has the aim to sequence all Norwegian eukaryotic species (estimated to be 45,000 in total). Knowing the complete DNA sequences of all species of life on Earth will provide the ultimate fundament for addressing biological questions of all kinds and will represent an unprecedented gold-mine of scientific data for biotechnology, medicine, and drug development, bioprospecting, new biomaterials, biofuels, and bioproduction (including aquaculture, horticulture and livestock production). By joining this project, you will become part of a multi-disciplinary team to advance our knowledge of global biodiversity. You will develop and optimize workflows to automate the assembly, annotation, and visualization of newly sequenced genomes in EBPNor. You will improve genome annotation by drawing from ever-higher taxonomic coverage generated by EBPNor and its partner project. Our employees contribute to excellence through high-quality research and teaching. The working environment for this position will be within CBU.

See the announcement on JobbNorge for more information and to apply.

New insights into genome evolution and parasitism - the salmon louse genome delivers

Michael Dondrup — Wed, 15 Sep 2021 07:56:55 +0000

We are happy to announce that we have finally published a peer-reviewed research paper describing the Atlantic salmon louse genome in Genomics.
Even though copepods have many ecological roles and interest is on the rise, they are still not that well-represented in genome databases. The same is true for parasites, especially the marine species. The LSalAtl2s assembly has a size of 695.4 Mbp (million base pairs of DNA) and we have annotated 13,081 protein-coding genes.

Because of our commitment to open data, we have made the genome accessible early on, e.g., here in LiceBase and in Ensembl Metazoa.
Over the years, a lot of researchers world-wide have used LSalAtl2s for gene expression studies, to study different gene families, design RNAi experiments, or to map genetic markers. This also means that the genome has been extremely vetted. But simply having data is not enough, we needed some good scientific questions, bioinformatics analyses, and interpretations. We have long argued that the key to sea lice control is in the genome. In the following, I will summarize what are some -in my opinion- key findings from this project.

Nobody’s perfect

First off, no genome is 100% correct, there are often gaps, regions that are hard to sequence or to stitch together (assemble) from the fragments sequencing machines deliver.
We may also appreciate that every individual is also slightly different and usually also has variation between the two copies of their chromosomes. What is more, finding genes in sequences requires sophisticated computer algorithms and does not work well yet without a lot of training data and human intervention. New sequencing technology, like long-read sequencing, helps closing gaps, but even then, the genome is rather a model of someone’s DNA and genes.

We therefore tried to assess how complete our salmon louse genome is by using “Benchmarking Universal Single-Copy Ortholog” (BUSCO) tool. BUSCO tries to detect genes that could be found in all or most organisms in a lineage because they are highly conserved and delivers an estimate of complete the genome is.
LSalAtl2s contains approximately 92% complete BUSCO’s and only about 4% are completely missed, a value that is comparable to other arthropod genomes. Similar values have been achieved when mapping transcriptome (RNA-seq) and other sequencing data back to the genome.
Also, here at SLRC and internationally, many important genes have already been characterized, annotated, sequenced, published, and -where necessary- corrected.

But what exactly shapes a parasite genome, and which features make the salmon louse so competitive?

Repeats, the genomic dark matter

Only a tiny portion of genomes codes for proteins and RNA. Most plant and animal genomes contain repetitive sequences of various types and in various amounts. Some of these repeats can, and indeed will, at any given moment cut-and-paste or copy-and-paste themselves to different locations of the genomes, they are called transposable elements (TE). These have sometimes been called names, like “selfish genes” or “junk DNA”. But nowadays our views are shifting, and researchers have proposed that TE’s shape and accelerate genome evolution. They influence genome size, may make new copies of genes, and delete others, re-arrange them, or alter gene expression.

When we analyzed the salmon louse genome and other crustacean genomes, we found it has over 60% repetitive sequences. This is the highest percentage of all sequenced crustacean genomes so far and remarkable for a relatively small genome. Interestingly, the salmon genome, despite being over four times larger, has similar repeat content. While high repeat content is not restricted to parasites, it might give the salmon louse an edge in adaptation.

Less is more

One of the key features of parasite genomes seems to be to have less genes and proteins than free-living organisms. Using a larger dataset of parasites and free-living organisms, we could show for the first time that animal parasites have a significantly reduced set of genes, and especially a reduced proteome. Interestingly, the total length of the proteome was an even better indicator of lifestyle than just the number of predicted genes. One explanation is that parasites need less genes because they can exploit a host for nutrients and need a less complex metabolism. An example for this is that the louse is apparently lacking genes for making peroxisomes, organelles that are involved in breaking down long fatty acids.

Certainly, genomes and computer predicted gene-sets are often of varying quality and good parasite genomes are still a scarce commodity. Therefore, a wider diversity of lifestyles should be covered by future sequencing projects.

Strength in gene numbers, the key to resistance?

The salmon louse is highly capable of developing resistances against chemical delousing, doesn’t this mean it should have many copies of genes that help it deal with toxins?

We investigated this idea for several gene families related to coping with toxins or stress and, much to our surprise, found the opposite is the case. Some very important and well-known gene-families had reduced numbers when compared to free-living relatives. Only very few gene-families were expanded, and it will be exiting to focus on these in the future.

Here, I have depicted only a small part of our findings about the genome, and there is a host of exiting open questions and hypothesis for the sea lice community to investigate in the future, some of which we have pinpointed in the paper.

For citing the salmon louse genome, please refer to:

Rasmus Skern-Mauritzen, Ketil Malde, Christiane Eichner, Michael Dondrup, Tomasz Furmanek, Francois Besnier, Anna Zofia Komisarczuk, Michael Nuhn, Sussie Dalvin, Rolf B. Edvardsen, Sven Klages, Bruno Huettel, Kurt Stueber, Sindre Grotmol, Egil Karlsbakk, Paul Kersey, Jong S. Leong, Kevin A. Glover, Richard Reinhardt, Sigbjørn Lien, Inge Jonassen, Ben F. Koop, Frank Nilsen,
The salmon louse genome: Copepod features and parasitic adaptations,
Genomics,
Volume 113, Issue 6,
2021,
Pages 3666-3680,
ISSN 0888-7543,
https://doi.org/10.1016/j.ygeno.2021.08.002
(https://www.sciencedirect.com/science/article/pii/S0888754321003098)

Immune modulation by the salmon louse - time to shift targets

Michael Dondrup — Thu, 29 Apr 2021 08:04:55 +0000

A most remarkable feature of the Atlantic salmon louse is its ability to neutralize practically all immune responses by its host, the Atlantic salmon. Except for some very limited local reaction, the louse is barely visible to the immune system. What may be the result of millions of years of co-evolution and a molecular arms-race between parasite and host has resulted in some sort of armistice in favor of tolerating the parasite. How, and even if, the salmon louse actively gains the upper hand is not well understood. More and more evidence points into the direction that parasites can suppress, or “modulate”, the immune system of their host by excreted proteins or other compounds.

Prostaglandins are lipid compounds that have functions akin to hormones and are found in most animals, including the salmon louse. When they were first discovered in 1935, it was believed that they were exclusively secreted by the human prostate, and hence the name. Prostaglandins are expressed in many different tissues and have different roles in e.g. vasodilation and inflammation.

For some time now, an idea about prostaglandin E₂ (PGE₂), a subtype of prostaglandins found in the salmon louse, has been discussed at sea lice meetings and conferences. It is believed that the salmon louse can produce PGE₂ as it is released into sea water when stimulated with dopamine [1]. When salmon cells are treated with PGE₂ it is recognized by a receptor and the cells respond in a certain way depending on the concentration of PGE₂ [2]. Also, other arthropods, like ticks, have a similar trick and inject prostaglandins into their host while sucking blood [3]. Therefore, the salmon louse may do the same and suppress the immune system by injecting PGE₂into the salmon.

However, there is still lack of concrete evidence for this hypothesis. Therefore, in our new paper [4] we have tried to further investigate the role of prostaglandins by studying PGE₂ and salmon louse genes that could be responsible for PGE₂synthesis, the prostaglandin E₂ synthases (PGES). After an extensive search in the genome, we found in total three putative PGES’, two of these new and one already described [5]. When looking at their gene-expression, none of the PGES’ had a pattern that one would expect for a gene involved in the host-parasite interaction as none of the genes increased their expression levels immediate to or after infection, nor were the genes expressed in glands. Instead, they were expressed in reproductive tissues and intestine. And most importantly, when we knocked down the PGES genes by RNA-interference, no effects were observed on the infestation success nor the skin immune response.

But then, what is the function of prostaglandins in the salmon louse? When we knocked down another gene, which is known to result in oxidative stress in the louse [6], we saw that PGES genes were up regulated. Therefore, we concluded that the function of PGES is rather internal to the louse: related to stress response and reproduction.

In consequence, proving involvement of PGES or PGE₂in immune modulation might seem like a long shot. And even if PGE₂has an immune-modulative role, it is simply not a suitable target for intervention. The reason for this is: prostaglandins are compounds, not proteins, and as such the prostaglandins found in the salmon are surely chemically identical to those from the louse, and there might not be a good way to intervene without affecting the salmon as well.

In conclusion, we think it is about time to shift targets. One should keep in mind that there are more than 13,000 protein coding genes in LiceBase. Most of them have not been characterized in any way. Therefore, we are actively working on identification and characterization of novel factors within the project ModuLus to better understand the tricks of immune modulation, new knowledge that will pave the way for better management of this parasite.

List of genes

· EMLSAG00000006733 - LsMGST1L

· EMLSAG00000000441 - LsPGES2

· EMLSAG00000012943 - LsPGES3L

References

[1] Fast, M. D., N. W. Ross, C. A. Craft, S. J. Locke, S. L. MacKinnon, and S. C. Johnson. “Lepeophtheirus Salmonis: Characterization of Prostaglandin E2 in Secretory Products of the Salmon Louse by RP-HPLC and Mass Spectrometry.” Experimental Parasitology 107, no. 1–2 (2004): 5–13. https://doi.org/10.1016/j.exppara.2004.04.001.

[2] Fast, M. D., N. W. Ross, and S. C. Johnson. “Prostaglandin E2 Modulation of Gene Expression in an Atlantic Salmon (Salmo Salar) Macrophage-like Cell Line (SHK-1).” Developmental and Comparative Immunology 29, no. 11 (2005): 951–63. https://doi.org/10.1016/j.dci.2005.03.007.

[3] Poole, Nina M., Gayatri Mamidanna, Richard A. Smith, Lewis B. Coons, and Judith A. Cole. “Prostaglandin E2 in Tick Saliva Regulates Macrophage Cell Migration and Cytokine Profile.” Parasites and Vectors 6, no. 1 (2013): 261. https://doi.org/10.1186/1756-3305-6-261.

[4] Dalvin, Sussie, Christiane Eichner, Michael Dondrup, and Aina-Cathrine Øvergård. “Roles of Three Putative Salmon Louse (Lepeophtheirus Salmonis) Prostaglandin E2 Synthases in Physiology and Host–Parasite Interactions.” Parasites & Vectors 14, no. 1 (December 19, 2021): 206. https://doi.org/10.1186/s13071-021-04690-w.

[5] Eichner, Christiane, Aina Cathrine Øvergård, Frank Nilsen, and Sussie Dalvin. “Molecular Characterization and Knock-down of Salmon Louse (Lepeophtheirus Salmonis) Prostaglandin E Synthase.” Experimental Parasitology 159 (December 1, 2015): 79–93. https://doi.org/10.1016/j.exppara.2015.09.001.

[6] Øvergård, Aina Cathrine, Christiane Eichner, Frank Nilsen, and Sussie Dalvin. “Molecular Characterization and Functional Analysis of a Salmon Louse (Lepeophtheirus Salmonis, Krøyer 1838) Heme Peroxidase with a Potential Role in Extracellular Matrixes.” Comparative Biochemistry and Physiology -Part A : Molecular and Integrative Physiology 206 (April 1, 2017): 1–10. https://doi.org/10.1016/j.cbpa.2017.01.004.

Pre-print of the salmon louse genome paper available on bioRxiv

Michael Dondrup — Thu, 18 Mar 2021 13:41:27 +0000

A pre-print of the salmon louse genome paper has been posted to bioRxiv:
The salmon louse genome: copepod features and parasitic adaptations.
doi: https://doi.org/10.1101/2021.03.15.435234

Additional data is available in Zenodo:

[NEWS] The salmon louse - a spotlight on blood-feeding

Michael Dondrup — Tue, 12 May 2020 07:55:54 +0000

The salmon louse is feeding on blood from its host during the later parts of its life-cycle. Blood-feeding is a common strategy among arthropods. Blood is a rich source of nutrients for the parasite, among them proteins, lipids, iron, and other metal-containing molecules. But iron and heme that are present in the blood in large amounts can also be toxic. In a new study, we have investigated how the settlement site on the fish affects the blood-feeding of the salmon louse [1]. In an infection trial, we studied lice larvae attached to the skin and compared them with lice that we put on the gills of the fish. Gill tissue is rich with blood-vessels, and therefore, the parasite gains access to blood much earlier than it normally would. We sequenced and analyzed the transcriptome of the parasite using high-throughput sequencing that creates millions of short sequences and allows us to study how gene expression across the entire genome changes between lice settling on the skin and those on the gills.

Interestingly, we found that chalimus larvae that settle on the gills and prematurely gain access to blood develop much slower than those on the salmon skin. Also, gene expression is remarkably different between these groups of animals. We detected several hundred genes that were differentially expressed at different developmental stages and between settlement sites. Among those are well-known iron handling proteins like ferritins [2], or the heme scavenger receptor LsHSCARB that we have recently discovered [3].

Gill settlement results in a difference in gene expression and affects vital biological pathways. We conclude that premature blood-feeding likely causes the parasite to develop at a slower pace.

[1] Heggland, Erna Irene, Michael Dondrup, Frank Nilsen, and Christiane Eichner. “Host Gill Attachment Causes Blood-Feeding by the Salmon Louse (Lepeophtheirus Salmonis) Chalimus Larvae and Alters Parasite Development and Transcriptome.” Parasites & Vectors 13, no. 1 (2020): 225. https://doi.org/10.1186/s13071-020-04096-0.
[2] Heggland, Erna Irene, Christiane Tröße, Christiane Eichner, and Frank Nilsen. “Heavy and Light Chain Homologs of Ferritin Are Essential for Blood-Feeding and Egg Production of the Ectoparasitic Copepod Lepeophtheirus Salmonis.” Molecular and Biochemical Parasitology 232 (September 1, 2019): 111197. https://doi.org/10.1016/j.molbiopara.2019.111197.
[3] Heggland, Erna Irene, Christiane Eichner, Svein Isungset Støve, Aurora Martinez, Frank Nilsen, and Michael Dondrup. “A Scavenger Receptor B (CD36)- like Protein Is a Potential Mediator of Intestinal Heme Absorption in the Hematophagous Ectoparasite Lepeophtheirus Salmonis.” Scientific Reports 9 (2019): 1823. https://doi.org/10.1038/s41598-019-40590-x.

Minor problem with the basket

Michael Dondrup — Mon, 01 Apr 2019 19:11:27 +0000

There have been reports of an unreliable gene basket (shopping cart). Sometimes, the contents of the basket could be truncated or lost at seemingly random intervals, when using the gene search. I have tracked down the problem to a marginal issue with the Tripal logo in the footer of the site: https://github.com/tripal/tripal/issues/918

The problem should now be fixed and the basket contents should be safe. The contents will also be properly preserved between logins (but not when you create a basket as an anonymous user and then log in, as intended). Please let us know if you experience any problems with the basket.