Xenbase is a
Model Organism Database (MOD), providing informatics resources, as well as genomic and biological data on
Xenopus
''Xenopus'' () (Gk., ξενος, ''xenos''=strange, πους, ''pous''=foot, commonly known as the clawed frog) is a genus of highly aquatic frogs native to sub-Saharan Africa. Twenty species are currently described within it. The two best-kno ...
frogs.
[K. Karimi et al. (2017]
Xenbase: a genomic, epigenomic and transcriptomic model organism database
Nucleic Acids Research (NAR), gkx936
Xenbase has been available since 1999, and covers both
X. laevis
The African clawed frog (''Xenopus laevis'', also known as the 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 three short claws ...
and
X. tropicalis
The western clawed frog (''Xenopus tropicalis'') 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 ploidy#Diploid, diploid genome. Its genome has been sequenc ...
Xenopus varieties. 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.
[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 Other than hosting genomics data and tools, Xenbase supports the Xenopus research community though profiles for researchers and laboratories, and job and events postings.
Xenbase's Software and Hardware Platform
Xenbase runs in a cloud environment.
Its virtual machines are running in a
VMware
VMware, Inc. is an American cloud computing and virtualization technology company with headquarters in Palo Alto, California. VMware was the first commercially successful company to virtualize the x86 architecture.
VMware's desktop software ru ...
vSphere
VMware vSphere (formerly VMware Infrastructure 4) is VMware's cloud computing virtualization platform.
It includes an updated vCenter Configuration Manager, as well as vCenter Application Discovery Manager, and the ability of vMotion to move ...
environment on two servers, with automatic
load balancing and
fault tolerance
Fault tolerance is the property that enables a system to continue operating properly in the event of the failure of one or more faults within some of its components. If its operating quality decreases at all, the decrease is proportional to the ...
. Xenbase software uses
Java
Java (; id, Jawa, ; jv, ꦗꦮ; su, ) is one of the Greater Sunda Islands in Indonesia. It is bordered by the Indian Ocean to the south and the Java Sea to the north. With a population of 151.6 million people, Java is the world's mo ...
,
JSP,
JavaScript
JavaScript (), often abbreviated as JS, is a programming language that is one of the core technologies of the World Wide Web, alongside HTML and CSS. As of 2022, 98% of Website, websites use JavaScript on the Client (computing), client side ...
,
AJAX
Ajax may refer to:
Greek mythology and tragedy
* Ajax the Great, a Greek mythological hero, son of King Telamon and Periboea
* Ajax the Lesser, a Greek mythological hero, son of Oileus, the king of Locris
* ''Ajax'' (play), by the ancient Gree ...
,
XML
Extensible Markup Language (XML) is a markup language and file format for storing, transmitting, and reconstructing arbitrary data. It defines a set of rules for encoding documents in a format that is both human-readable and machine-readable. ...
, and
CSS
Cascading Style Sheets (CSS) is a style sheet language used for describing the presentation of a document written in a markup language such as HTML or XML (including XML dialects such as SVG, MathML or XHTML). CSS is a cornerstone t ...
. It also uses
IBM's
WebSphere Application Server and the
IBM DB2
Db2 is a family of data management products, including database servers, developed by IBM. It initially supported the relational model, but was extended to support object–relational features and non-relational structures like JSON and ...
database. The same hardware and software platforms support
Echinobase.
Xenopus as a Model Organism
The Xenopus
model organism is responsible for large amounts of new knowledge on embryonic development and cell biology.
Xenopus
''Xenopus'' () (Gk., ξενος, ''xenos''=strange, πους, ''pous''=foot, commonly known as the clawed frog) is a genus of highly aquatic frogs native to sub-Saharan Africa. Twenty species are currently described within it. The two best-kno ...
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.
Morpholino
A Morpholino, also known as a Morpholino oligomer and as a phosphorodiamidate Morpholino oligomer (PMO), is a type of oligomer molecule (colloquially, an oligo) used in molecular biology to modify gene expression. Its molecular structure contains ...
s 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
Small interfering RNA (siRNA), sometimes known as short interfering RNA or silencing RNA, is a class of double-stranded RNA at first non-coding RNA molecules, typically 20-24 (normally 21) base pairs in length, similar to miRNA, and operating ...
or
miRNA
MicroRNA (miRNA) are small, single-stranded, non-coding RNA molecules containing 21 to 23 nucleotides. Found in plants, animals and some viruses, miRNAs are involved in RNA silencing and post-transcriptional regulation of gene expression. miR ...
have yet been shown to reproducibly function in frog embryos. 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
Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product that enables it to produce end products, protein or non-coding RNA, and ultimately affect a phenotype, as the final effect. ...
. The large size of embryos and amenability to microinjection also makes them extremely well suited to
microarray
A microarray is a multiplex lab-on-a-chip. Its purpose is to simultaneously detect the expression of thousands of genes from a sample (e.g. from a tissue). It is a two-dimensional array on a solid substrate—usually a glass slide or silic ...
approaches. Furthermore, these same characteristics make Xenopus, one of the few vertebrate model organisms suited for chemical screens. Xenbase provides a large database of images illustrating the full genome, movies detailing
embryogenesis
An embryo is an initial stage of development of a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male sperm ...
, 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. Xenbase supports this by mapping
Disease Ontology and
OMIM
Online Mendelian Inheritance in Man (OMIM) is a continuously updated catalog of human genes and genetic disorders and traits, with a particular focus on the gene-phenotype relationship. , approximately 9,000 of the over 25,000 entries in OMIM ...
diseases to Xenopus genes and publications. Xenopus
phenotype
In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological prop ...
data, as well as links to comparable human and mouse phenotypes and diseases (via
the Monarch Initiative
The Monarch Initiative is a large scale bioinformatics web resource focused on leveraging existing biomedical knowledge to connect genotypes with phenotypes in an effort to aid research that combats genetic diseases.
Monarch does this by integrati ...
) 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. A detailed introduction to using Xenabse comes in.
[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
*
Phenotype
In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological prop ...
support, including
Monarch Initiative (human and mouse) data links
*Diseases - Users can search for both
Disease Ontology and
OMIM
Online Mendelian Inheritance in Man (OMIM) is a continuously updated catalog of human genes and genetic disorders and traits, with a particular focus on the gene-phenotype relationship. , approximately 9,000 of the over 25,000 entries in OMIM ...
diseases to find relevant Xenopus genes and publications
*
NGS RNA-Seq
RNA-Seq (named as an abbreviation of RNA sequencing) is a sequencing technique which uses next-generation sequencing (NGS) to reveal the presence and quantity of RNA in a biological sample at a given moment, analyzing the continuously changing ...
and
ChIP-Seq data integration and visualization from
Gene Expression Omnibus (GEO).
[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
*RNA-Seq viewers - Graphs of temporal expression profiles and spatial (anatomy) expression heatmaps for both laevis and tropicalis
*Gene Expression - Xenbase supports search and visualization of Gene Expression Omnibus (GEO) data sets, mapped to the latest Xenopus genomes.
*BLAST - Users can BLAST against Xenopus genomes, RNA, and protein sequences
*Genome browser - Xenbase uses both JBrowse and GBrowse
*Expression Search and Clone Search - Search by gene symbol, gene name, anatomy item, etc.
*Gene nomenclature guidelines - Xenbase is the official body responsible for Xenopus gene naming
*Literature search: Textpresso- Uses an algorithm to match your search to specific criteria or section of a paper. For example, you could identify papers describing HOX genes and limit your results to only papers which used morpholinos.
*Anatomy and Development: Images, fate maps, videos, etc.
*Community Link - People, jobs, labs which study Xenopus
*Protocol List- Identify clones, antibodies, procedures
*Stock Center- Supports the National Xenopus Resource, the European Xenopus Resource Centre, etc. to help researchers with obtaining frog stocks or advanced research training
2012 Nobel Prize in Xenopus Research
The Nobel Prize for Medicine or Physiology was awarded to
John B. Gurdon
Sir John Bertrand Gurdon (born 2 October 1933) is a British developmental biologist. He is best known for his pioneering research in nuclear transplantation and cloning. He was awarded the Lasker Award in 2009. In 2012, he and Shinya Yamanaka ...
and Shinya Yamanaka on October 8, 2012. for nuclear reprogramming in Xenopus.
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.
* Genetic Screens for Mutations Affecting Development of ''X. tropicalis''.
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.
* High efficiency
TALENs enable F0 functional analysis by targeted gene disruption in Xenopus laevis embryos.
The 2013 paper by Suzuki et al. describes the use of a relatively new gene knockdown technique in ''X. laevis''. Traditionally, antisense
morpholino
A Morpholino, also known as a Morpholino oligomer and as a phosphorodiamidate Morpholino oligomer (PMO), is a type of oligomer molecule (colloquially, an oligo) used in molecular biology to modify gene expression. Its molecular structure contains ...
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.
[Huang, P., A. Xiao, et al. (2011). "Heritable gene targeting in zebrafish using customized TALENs." Nat Biotech 29(8): 699-700] Xenbase was utilized to obtain publicly available sequences for tyrosinase (tyr) and ''
Pax6
Paired box protein Pax-6, also known as aniridia type II protein (AN2) or oculorhombin, is a protein that in humans is encoded by the ''PAX6'' gene.
Function
PAX6 is a member of the Pax gene family which is responsible for carrying the genet ...
'', 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
*
Echinobase
*
FlyBase
FlyBase is an online bioinformatics database and the primary repository of genetic and molecular data for the insect family Drosophilidae. For the most extensively studied species and model organism, ''Drosophila melanogaster'', a wide range of d ...
*
WormBase
*
Mouse Genome Informatics
Mouse Genome Informatics (MGI) is a free, online database and bioinformatics resource hosted by The Jackson Laboratory, with funding by the National Human Genome Research Institute (NHGRI), the National Cancer Institute (NCI), and the Eunice Kenned ...
*
ZFIN
*
DictyBase
References
{{reflist, refs=
*{{cite journal , title=Xenbase: gene expression and improved integration , journal=Nucleic Acids Research , volume=38 , issue=Database issue , pages=D607–D612 , author=Jeff B. Bowes, Kevin A. Snyder, Erik Segerdell, Chris J. Jarabek, Kenan Azam, Aaron M. Zorn and Peter D. Vize , url= , doi=10.1093/nar/gkp953 , pmid=19884130 , pmc=2808955 , year=2010
Cell biology
Model organism databases
Vertebrate developmental biology
Biological databases