Xenbase

Last updated
Xenbase
XenbaseLogo.png
Content
DescriptionXenbase: The Xenopus Model Organism Knowledgebase.
Data types
captured
Phenotypes, Diseases, Literature, Nucleotide Sequence, RNA sequence, Protein sequence, Structure, Genomics, Morpholinos, Metabolic and Signaling Pathways, Human and other Vertebrate Genomes, Human Genes and Diseases, Microarray Data and other Gene Expression, Proteomics Resources, Other Molecular Biology, Organelle
Organisms Xenopus laevis and Xenopus tropicalis
Contact
Research center Cincinnati Children's Hospital, University of Calgary
Laboratory Zorn lab, Vize lab
Primary citation PMID   29059324
Release date1999
Access
Website https://www.xenbase.org/
Download URL https://download.xenbase.org/xenbase/
Tools
Standalone BLAST, JBrowse
Miscellaneous
License Public domain
Data release
frequency
Continuous
Version6.x
Curation policyProfessionally curated
Bookmarkable
entities
Yes

Xenbase is a Model Organism Database (MOD), providing informatics resources, as well as genomic and biological data on Xenopus frogs. [1] Xenbase has been available since 1999, and covers both X. laevis and X. tropicalis Xenopus varieties. [2] As of 2013 all of its services are running on virtual machines in a private cloud environment, making it one of the first MODs to do so. [3] Other than hosting genomics data and tools, Xenbase supports the Xenopus research community though profiles for researchers and laboratories, and job and events postings.

Contents

Xenbase's Software and Hardware Platform

Xenbase runs in a cloud environment. [3] Its virtual machines are running in a VMware vSphere environment on two servers, with automatic load balancing and fault tolerance. Xenbase software uses Java, JSP, JavaScript, AJAX, XML, and CSS. It also uses Apache Tomcat and the IBM DB2 database. The same hardware and software platforms support Echinobase.

Supported Species

Xenbase offers two levels of support. Full support includes full genome integration in the database, including gene pages, BLAST, JBrowse, and genome downloads. Partial support provides BLAST, JBrowse, and download options, but no gene page integration.

Full support: Xenbase's primary mission is to provide comprehensive support for the following frogs

Partial support:

Xenopus as a Model Organism

The Xenopus model organism is responsible for large amounts of new knowledge on embryonic development and cell biology. Xenopus has a number of unique experimental advantages as a vertebrate model. Paramount among these is the robustness of early embryos and their amenability to microinjection and microsurgery. This makes them a particularly attractive system for testing the ectopic activity of gene products and loss-of-function experiments using antagonizing reagents such as morpholinos, dominant-negatives and neomorphic proteins. Morpholinos are synthetic oligonucleotides that can be used to inhibit nuclear RNA splicing or mRNA translation and are the common gene inhibition reagent in Xenopus as neither siRNA or miRNA have yet been shown to reproducibly function in frog embryos. [4] Xenopus embryos develop very quickly and form a full set of differentiated tissues within days of fertilization, allowing rapid analysis of the effects of manipulating embryonic gene expression. [5] The large size of embryos and amenability to microinjection also makes them extremely well suited to microarray approaches. Furthermore, these same characteristics make Xenopus, one of the few vertebrate model organisms suited for chemical screens. [6] Xenbase provides a large database of images illustrating the full genome, movies detailing embryogenesis, and multiple online tools useful for designing and conducting experiments using Xenopus.

Xenopus as a Human Disease Model

Xenopus can be used to model human diseases caused by common genes. [7] Xenbase supports this by mapping Disease Ontology and OMIM diseases to Xenopus genes and publications. Xenopus phenotype data, as well as links to comparable human and mouse phenotypes and diseases (via the Monarch Initiative) are also provided.

Xenbase Contents and Tools

Xenbase provides many tools useful for both professional research as well as academic learning. Highlighted below are a few of the tools, along with a brief description. For full details on provided tools, users are referred to Xenbase's publications. [8] A detailed introduction to using Xenabse comes in. [9]

2012 Nobel Prize in Xenopus Research

The Nobel Prize for Medicine or Physiology was awarded to John B. Gurdon and Shinya Yamanaka on October 8, 2012. [12] for nuclear reprogramming in Xenopus. [13]

Importance: Gurdon's experiments challenged the dogma of the time which suggested that the nucleus of a differentiated cell is committed to their fate (Example: a liver cell nucleus remains a liver cell nucleus and cannot return to an undifferentiated state).

Specifically, John Gurdon's experiments showed that a mature or differentiated cell nucleus can be returned to its immature undifferentiated form; this is the first instance of cloning of a vertebrate animal.

Experiment: Gurdon used a technique known as nuclear transfer to replace the killed-off nucleus of a frog (Xenopus) egg with a nucleus from a mature cell (intestinal epithelial). The tadpoles resulting from these eggs did not survive long (past the gastrulation stage), however, further transformation of the nuclei from these Xenopus eggs to a second set of Xenopus eggs resulted in fully developed tadpoles. This process (transfer of nuclei from cloned cells) is referred to as serial transplantation.

Xenopus Research Utilizing Xenbase Tools

To provide examples of how Xenbase could be used to facilitate academic research, two research articles are briefly described below.

This paper uses Xenbase resources to create and characterize mutations in Xenopus tropicalis. Goda et al., performed a large scale forward genetics screen on X. tropicalis embryos to identify novel mutations (2006). Defects were noted and put into 10 different categories as follows: eye, ear, neural crest/pigment, dwarf, axial, gut, cardiovascular, head, cardiovascular plus motility, and circulation. Further studies were performed on the whitehart mutant "wha" which does not have normal circulating blood. The Xenopus Molecular Marker Resource page was used to design a microarray experiment which compared wild type (normal circulation) and "wha" mutant X. tropicalis. Analysis of microarray data revealed that 216 genes had significant changes in expression, with genes involved in hemoglobin and heme biosynthesis being the most affected, consistent with the observation that "wha" may have a role in hematopoiesis.

The 2013 paper by Suzuki et al. describes the use of a relatively new gene knockdown technique in X. laevis. Traditionally, antisense morpholino oligonucleotides have been the method of choice to study the effects of transient gene knockdown in Xenopus.

In comparison to morpholinos which disrupt gene expression by inhibiting translational machinery TALENs disrupt gene expression by binding to DNA and introducing double stranded breaks. [16] [17] Xenbase was utilized to obtain publicly available sequences for tyrosinase (tyr) and Pax6 , needed for TALEN design. Knockdown of both Pax6 and tyr was highly efficient using TALENs, suggesting that gene disruption using TALENs may be an alternative or better method to use in comparison to antisense morpholino's.

See also

Related Research Articles

<span class="mw-page-title-main">African clawed frog</span> Species of amphibian

The African clawed frog, also known as simply Xenopus, African clawed toad, African claw-toed frog or the Platanna) is a species of African aquatic frog of the family Pipidae. Its name is derived from the short black claws on its feet. The word Xenopus means 'strange foot' and laevis means 'smooth'.

<i>Xenopus</i> Genus of amphibians

Xenopus is a genus of highly aquatic frogs native to sub-Saharan Africa. Twenty species are currently described within it. The two best-known species of this genus are Xenopus laevis and Xenopus tropicalis, which are commonly studied as model organisms for developmental biology, cell biology, toxicology, neuroscience and for modelling human disease and birth defects.

<span class="mw-page-title-main">Biological database</span>

Biological databases are libraries of biological sciences, collected from scientific experiments, published literature, high-throughput experiment technology, and computational analysis. They contain information from research areas including genomics, proteomics, metabolomics, microarray gene expression, and phylogenetics. Information contained in biological databases includes gene function, structure, localization, clinical effects of mutations as well as similarities of biological sequences and structures.

Gene knockdown is an experimental technique by which the expression of one or more of an organism's genes is reduced. The reduction can occur either through genetic modification or by treatment with a reagent such as a short DNA or RNA oligonucleotide that has a sequence complementary to either gene or an mRNA transcript.

<span class="mw-page-title-main">Functional genomics</span> Field of molecular biology

Functional genomics is a field of molecular biology that attempts to describe gene functions and interactions. Functional genomics make use of the vast data generated by genomic and transcriptomic projects. Functional genomics focuses on the dynamic aspects such as gene transcription, translation, regulation of gene expression and protein–protein interactions, as opposed to the static aspects of the genomic information such as DNA sequence or structures. A key characteristic of functional genomics studies is their genome-wide approach to these questions, generally involving high-throughput methods rather than a more traditional "candidate-gene" approach.

The transcriptome is the set of all RNA transcripts, including coding and non-coding, in an individual or a population of cells. The term can also sometimes be used to refer to all RNAs, or just mRNA, depending on the particular experiment. The term transcriptome is a portmanteau of the words transcript and genome; it is associated with the process of transcript production during the biological process of transcription.

<span class="mw-page-title-main">Morpholino</span> Chemical compound

A Morpholino, also known as a Morpholino oligomer and as a phosphorodiamidate Morpholino oligomer (PMO), is a type of oligomer molecule used in molecular biology to modify gene expression. Its molecular structure contains DNA bases attached to a backbone of methylenemorpholine rings linked through phosphorodiamidate groups. Morpholinos block access of other molecules to small specific sequences of the base-pairing surfaces of ribonucleic acid (RNA). Morpholinos are used as research tools for reverse genetics by knocking down gene function.

<span class="mw-page-title-main">Silencer (genetics)</span> Type of DNA sequence

In genetics, a silencer is a DNA sequence capable of binding transcription regulation factors, called repressors. DNA contains genes and provides the template to produce messenger RNA (mRNA). That mRNA is then translated into proteins. When a repressor protein binds to the silencer region of DNA, RNA polymerase is prevented from transcribing the DNA sequence into RNA. With transcription blocked, the translation of RNA into proteins is impossible. Thus, silencers prevent genes from being expressed as proteins.

<span class="mw-page-title-main">Animal testing on frogs</span> Overview article

Frogs have been used in animal tests throughout the history of biomedical science.

<span class="mw-page-title-main">Zebrafish Information Network</span> Model organism database on zebrafish

The Zebrafish Information Network is an online biological database of information about the zebrafish. The zebrafish is a widely used model organism for genetic, genomic, and developmental studies, and ZFIN provides an integrated interface for querying and displaying the large volume of data generated by this research. To facilitate use of the zebrafish as a model of human biology, ZFIN links these data to corresponding information about other model organisms and to human disease databases. Abundant links to external sequence databases and to genome browsers are included. Gene product, gene expression, and phenotype data are annotated with terms from biomedical ontologies. ZFIN is based at the University of Oregon in the United States, with funding provided by the National Institutes of Health (NIH).

<span class="mw-page-title-main">Western clawed frog</span> Species of amphibian

The western clawed frog is a species of frog in the family Pipidae, also known as tropical clawed frog. It is the only species in the genus Xenopus to have a diploid genome. Its genome has been sequenced, making it a significant model organism for genetics that complements the related species Xenopus laevis, a widely used vertebrate model for developmental biology. X. tropicalis also has a number of advantages over X. laevis in research, such as a much shorter generation time, smaller size, and a larger number of eggs per spawn.

<span class="mw-page-title-main">RNA-Seq</span> Lab technique in cellular biology

RNA-Seq is a technique that uses next-generation sequencing to reveal the presence and quantity of RNA molecules in a biological sample, providing a snapshot of gene expression in the sample, also known as transcriptome.

<span class="mw-page-title-main">Genetically modified animal</span> Animal that has been genetically modified

Genetically modified animals are animals that have been genetically modified for a variety of purposes including producing drugs, enhancing yields, increasing resistance to disease, etc. The vast majority of genetically modified animals are at the research stage while the number close to entering the market remains small.

<span class="mw-page-title-main">Ectoderm specification</span> Stage in embryonic development

In Xenopus laevis, the specification of the three germ layers occurs at the blastula stage. Great efforts have been made to determine the factors that specify the endoderm and mesoderm. On the other hand, only a few examples of genes that are required for ectoderm specification have been described in the last decade. The first molecule identified to be required for the specification of ectoderm was the ubiquitin ligase Ectodermin ; later, it was found that the deubiquitinating enzyme, FAM/USP9x, is able to overcome the effects of ubiquitination made by Ectodermin in Smad4. Two transcription factors have been proposed to control gene expression of ectodermal specific genes: POU91/Oct3/4 and FoxIe1/Xema. A new factor specific for the ectoderm, XFDL156, has shown to be essential for suppression of mesoderm differentiation from pluripotent cells.

GeneNetwork is a combined database and open-source bioinformatics data analysis software resource for systems genetics. This resource is used to study gene regulatory networks that link DNA sequence differences to corresponding differences in gene and protein expression and to variation in traits such as health and disease risk. Data sets in GeneNetwork are typically made up of large collections of genotypes and phenotypes from groups of individuals, including humans, strains of mice and rats, and organisms as diverse as Drosophila melanogaster, Arabidopsis thaliana, and barley. The inclusion of genotypes makes it practical to carry out web-based gene mapping to discover those regions of genomes that contribute to differences among individuals in mRNA, protein, and metabolite levels, as well as differences in cell function, anatomy, physiology, and behavior.

Model organism databases (MODs) are biological databases, or knowledgebases, dedicated to the provision of in-depth biological data for intensively studied model organisms. MODs allow researchers to easily find background information on large sets of genes, plan experiments efficiently, combine their data with existing knowledge, and construct novel hypotheses. They allow users to analyse results and interpret datasets, and the data they generate are increasingly used to describe less well studied species. Where possible, MODs share common approaches to collect and represent biological information. For example, all MODs use the Gene Ontology (GO) to describe functions, processes and cellular locations of specific gene products. Projects also exist to enable software sharing for curation, visualization and querying between different MODs. Organismal diversity and varying user requirements however mean that MODs are often required to customize capture, display, and provision of data.

Perturb-seq refers to a high-throughput method of performing single cell RNA sequencing (scRNA-seq) on pooled genetic perturbation screens. Perturb-seq combines multiplexed CRISPR mediated gene inactivations with single cell RNA sequencing to assess comprehensive gene expression phenotypes for each perturbation. Inferring a gene’s function by applying genetic perturbations to knock down or knock out a gene and studying the resulting phenotype is known as reverse genetics. Perturb-seq is a reverse genetics approach that allows for the investigation of phenotypes at the level of the transcriptome, to elucidate gene functions in many cells, in a massively parallel fashion.

<span class="mw-page-title-main">Zinc transporter ZIP12</span> Protein found in humans

Solute carrier family 39 member 12 is a protein that in humans is encoded by the SLC39A12 gene.

Echinobase is a Model Organism Database (MOD). It supports the international research community by providing a centralized, integrated web based resource to access the diverse and rich, functional genomics data of echinoderm evolution, development and gene regulatory networks.

References

  1. M. Fisher et al. (2023) Xenbase: key features and resources of the Xenopus model organism knowledgebase, Genetics, Volume 224, Issue 1, May 2023, iyad018,
  2. P.D. Vize et al. (2015) Database and informatic challenges in representing both diploid and tetraploid Xenopus species in Xenbase, Cytogenet Genome Res 2015;145:278-282
  3. 1 2 K. Karimi and P.D. Vize (2014). The Virtual Xenbase: transitioning an online bioinformatics resource to a private cloud, Database, doi: 10.1093/database/bau108
  4. Eisen, J.a.S., J. . (2008). Controlling morpholino experiments: don't stop making antisense. Development, 135(10): p. 1735-1743.
  5. Gene expression data for Pax8 gene on xenbase's site
  6. Wheeler, G. N. and A. W. Brändli (2009). "Simple vertebrate models for chemical genetics and drug discovery screens: Lessons from zebrafish and Xenopus." Developmental dynamics 238(6): 1287-1308.
  7. Nenni et al. (2019). Xenbase: Facilitating the use of Xenopus to Model Human Disease, Frontiers in Physiology, Volume 10, doi:10.3389/fphys.2019.00154
  8. "Xenbase publications".
  9. James-Zorn et al. (2018) Navigating Xenbase: An Integrated Xenopus Genomics and Gene Expression Database, Eukaryotic Genomic Databases: Methods and Protocols, Volume 1757, Chapter 10, pp. 251-305, doi:10.1007/978-1-4939-7737-6
  10. M. Fisher et al. (2022) The Xenopus phenotype ontology: bridging model organism phenotype data to human health and development, BMC bioinformatics, 23, 99
  11. Fortriede et al. (2020) Xenbase: deep integration of GEO & SRA RNA-seq and ChIP-seq data in a model organism database, Nucleic Acids Research (NAR), Volume 48, Issue D1, 08 January 2020, Pages D776–D782, doi:https://doi.org/10.1093/nar/gkz933
  12. "The 2012 Nobel Prize in Physiology or Medicine - Press Release".
  13. Gurdon, J.B. (1962). The Developmental Capacity of Nuclei taken from Intestinal Epithelium Cells of Feeding Tadpoles. Journal of Embryology and Experimental Morphology, 10(4): p. 622-640
  14. Goda, T., Abu-Daya, Anita, Carruthers, Samantha, Clark, Matthew D., Stemple, Derek L., Zimmerman, Lyle B. (2006). " Genetic Screens for Mutations Affecting Development of Xenopus tropicalis." PLoS Genet 2(6): e91
  15. Suzuki, K.-i. T., Y. Isoyama, et al. (2013). "High efficiency TALENs enable F0 functional analysis by targeted gene disruption in Xenopus laevis embryos." Biology Open
  16. Boch, J. (2011). "TALEs of genome targeting." Nat Biotech 29(2): 135-136
  17. Huang, P., A. Xiao, et al. (2011). "Heritable gene targeting in zebrafish using customized TALENs." Nat Biotech 29(8): 699-700