Reconstruction of a fish protein interactome

In recent years a range of different fish species have become promising vertebrate models in biology, supported by the sequencing, assembly and annotation of several fish genomes. Scientists at the University of Liverpool have pioneered the creation of genomic resources for various Euteleostean species (trout, carp, flounder, zebrafish, eel) including customised microarrays which generated unique data sets relating to abiotic stress responses, ecotoxicity, hydrostatic pressure, and disease tolerance. These datasets contains dimensions that have not been fully explored. This bioinformatics project will focus first on a thorough cross-species gene mapping of data from array repositories, and establishing homologies and paralogies across the wide taxonomic range of fishes. Second, it will seek to identify patterns of co-expression that are conserved across species. Using new methods of organism-specific functional networks and network alignment we will reconstruct a weighted fish-specific ‘reactome’ matrix. We will also seek to identify gene neighbourhoods in Danio rerio and Tetrodion genomes and use the conserved links as an additional indication of functional coupling between pairs of genes. This and expression meta-analysis data will help us to refine the fish interactome and to weight probabilities of predicted interactions.

We will adopt a new computational approach developed by Prof. Gasieniec’s group (Computer Sciences) to reconstruct and visualise the predicted networks. It will contain new capabilities, such as automatic outlines of clusters with a specific connectivity type and confidence level, quantitation of topological characteristics for any part of the network, prediction of potential regulators from a network context, etc. This PhD project will be closely associated with the further development of the software and its validation.

The project should lead to the development of the valuable resource for the systemic analysis of fish ‘Omics’ datasets and new advances in biological network interference technology which will have broad applications.


Training:
This project will provide a thorough training in bioinformatics, including gene discovery and annotation, collation and analysis of large-scale datasets, patterns-searching and statistical data processing techniques, visualisation techniques and creation of network descriptions and and introduction to a software development. If appropriate training in writing code will be given. A major focus is identifying questions that can be addressed through large data collations. Dr Olga Vasieva is a Senior Bioinformatician, Prof Cossins has led fish genomics work for >10 years, and Prof Gasieniec is an expert in algorithm development. The student will work within a large and active bioinformatics group incorporated into the MRC/NERC-supported Centre for Genome Research, and Prof Gasieniec’s group of software developers. He/she will benefit from frequent journal clubs and there are opportunities to join local and national courses in bioinformatics, and participate in elements of the bioinformatics Masters program. The project is integrated into the ERASYSBIO+ project “GRAPPLE” which involves developing new methods for data interrogation and network analysis with partners in Cambridge and Barcelona. This project would suit a student with a degree in Computer Science, Maths, Physics or Theoretical Physics, or Biologists with an interest and competence in informatics and computer studies.