Periodic Reporting for period 2 - ZENCODE-ITN (Computational and functional annotation of genomic elements during development of the model vertebrate zebrafish)
Reporting period: 2017-01-01 to 2018-12-31
In our programme we have created an unique compendium of zebrafish genomics database and resource which consists of new genomics data generated by the network partner laboratories and collation of most of the available published data meticulously assembled and re-analysed by standardised pipelines by network partners. From the new data we were able to deduce novel biological observations for example on the genetic basis of endoderm and primordial germ cell specification, functional genetics of muscle development and nuclear and chromosomal topology organisation during development of a vertebrate animal model. The generation of the zebrafish genomics resource led by ZENCODE-ITN partners encompassed a larger global network of collaborators beyond ZENCODE-ITN, and called DANIO-CODE. ZENCODE-ITN partners played crucial roles in creating to a publicly accessible DANIO-CODE data coordination centre and a searchable genomics resource for both zebrafish model users and the wider genomics community.
We have made substantial progress in the following scientific objectives:
Computational tools development:
- new data mining tool is in development for analysing in which tissues and when during development genes work
- we established a Data Coordination Centre (DCC) for collecting and standardizing zebrafish epigenome, transcriptome datasets,
- Software and data structures for anatomy specific gene expression analysis has been developed
- Computational pipeline has been created to compare spatio-temporal expression profiles and to identify co-expression groups
- genomics data visualisation tools have been developed for visualising multidimensional datasets
Experimental technology development and data collection:
- We have collected genome wide epigenetic data from a variety of tissues and cell types including primordial germ cells, pancreatic cell types, endoderm, muscle and nervous system
- We have developed new miniaturized biochemical techniques to collect genome wide data from small cell numbers (e.g. chromatin immunoprecipitation, promoter capture technology- CAGE and chromosome conformation capture assay)
- We have collected human non-coding functional elements for pancreatic islets to then study their function in a fish embryo model
Genome wide data annotation:
- ZENCODE-ITN partners progressed substantially with the comprehensive annotation of the zebrafish genome by seeding and leading the efforts of a global consortium effort under the umbrella of DANIO-CODE.
- ZENCODE-ITN members have played central and dominant role in initiating, establishing, coordinating managing and undertaking DANIO-CODE objectives (http://www.birmingham.ac.uk/generic/danio-code/data-coordination-centre.aspx)
- We have generated a catalog and classification of so called non-coding RNAs in nuclear and cytoplasmic fractions of developing embryos at various stages
- We have analysed sequence variants of human disease associated non-coding DNA elements which are predicted to regulate gene activity
- We have characterised the epigenetic landscape of primordial germ cells and identified key
- We have characterised transcription regulatory networks in endoderm development and pancreatic islet specification
- We have characterised zebrafish mutants affecting muscle development
by transcriptome analysis
Our DANIO-CODE portal allows easy access to processed zebrafish genomic and epigenomic data to wider scientific community and in this way will strengthen zebrafish as model organism for development.
Our efforts will have considerable impact on expansion of the use of zebrafish as genomics model and the generated public database of zebrafish genomics datasets will be a resource for the over thousand of zebrafish user laboratories and the even larger broader genomics community.
Dissemination:
Two international genomic conference were organized (see website https://zencode-itn.eu/conferences). At these meetings, all ZENCODE students presented the results of their work and had the opportunity to discuss with scientists expert in the genomic field.
Several peer reviewed publications resulted from the ZENCODE –ITN Project acknowledging the support of the ITN programme. A website was established https://zencode-itn.eu/; and also http://www.birmingham.ac.uk/generic/zencode-itn/index.aspx ). A twitter account was also developed to increase information exchange (https://twitter.com/zencodeitn). The ZENCODE-ITN students designed and produced an explainer video accessible at https://zencode-itn.eu/outreach.html and https://www.youtube.com/watch?v=antNReIh5VU.