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Computational and functional annotation of genomic elements during development of the model vertebrate zebrafish

Periodic Reporting for period 1 - ZENCODE-ITN (Computational and functional annotation of genomic elements during development of the model vertebrate zebrafish)

Reporting period: 2015-01-01 to 2016-12-31

The recent explosion of next generation sequencing (NGS) data has led to a critical shortage of computational biology expertise. As NGS methods are expected to become pervasive from basic science to personalised medicine there is an urgent need for highly skilled young scientists trained in both computational biology and experimental wet lab biology. Our network addresses this important problem of the postgenomic era. We aim to provide multi-disciplinary skills for a solid foundation in computational biology and developmental genomics. Developmental genomics is central to understanding of ontogeny and many genetic and congenital anomalies, but was outside the scope of the landmark ENCODE project. ENCODE highlighted the need for an in vivo vertebrate model that enables high throughput in vivo functional testing of hypotheses generated from genome scale annotation. Zebrafish is an ideal model for extending the scope of genomics to vertebrate development with high throughout capabilities. We aim to comprehensively annotate functional elements, decipher genomic codes of transcription, as well as coding and non-coding gene function during development and enhance zebrafish as an attractive developmental, comparative and disease model. The participants include SMEs, major zebrafish genomics laboratories, eminent computational biologists and world-class genomics technology experts active in FANTOM and ENCODE.
In the last two years the ZENCODE-ITN project has fulfilled its key objectives in recruitment 15 early stage researchers, training, setting up network communication channels, a website and student network, as well as social network media. All due deliverables and have been submitted and expected milestones completed. Three successful training events have been organised with firm plans in progress for further training events and a large international meeting in March 2017.
We have made progress in the following scientific objectives:
We are developing new methodologies for studying genome, epigenome and transcriptome dynamics during embryonic development
We work to decipher the genomic codes of transcription, coding and non-coding gene function during development by combination of multidisciplinary approaches in experimental developmental genetics and computational biology, taking advantage of zebrafish as a highly efficient model.
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
Experimental technology development and data collection:
- We are collecting genome wide epigenetic data (chromatin state, tramscripiton factor binding) from a variety of tissues and cell types including primordial germ cells, pancreatic cell types, endoderm, muscle and nervous system
- We are developing new miniaturized biochemical techniques to collect genome wide data from small cell numbers
- We are collecting human non coding functional elements for pancreatic islets to then study their function in a fish embryo model
Genome wide data annotation:
- We study repetitive elements, which represent a large chunk of the vertebrate genome
- We generate a catalog and classification of so called non-coding RNAs
- We analyse sequence variants of human disease associated non-coding DNA elements which are predicted to regulate gene activity

- To seed and progress with the comprehensive annotation of the zebrafish genome with functional elements, and enhance zebrafish as an attractive developmental, comparative and disease model.
Most substantial progress has been made towards this objective. ZENCODE-ITN members have played central and dominant role in initiating, establishing, coordinating managing and undertaking the objectives of a larger international network, DANIO-CODE, ( which aims for expansion of ZENCODE objectives on annotation of the zebrafish genome to the wider zebrafish genomics community. As a result of activities of ZENCODE-ITN members of the DANIO-CODE consortium, DANIO-CODE webpage was set up, consortium kick off meetings and workshops organized at international meetings, data upload jamboree were organized and held. Our main output with considerable impact is the establishment of a Data Coordination Centre ( which, as a result of ZENCODE-ITN activity, integrates all published zebrafish genomics datasets.