One of the major goals of biology, and consequently bioinformatics, is to successfully bridge the gap between genotype and phenotype. Microarray and Quantitative Trait Loci data are increasingly used to aid in the discovery of candidate genes that might be responsible for phenotypic differences. In previous years, studies into genotype-phenotype correlations have been conducted manually. This has led to problems with regards to the identification of functional candidate genes, primarily due to the scale of data being investigated and the reliance on specific expertise, which may bias the investigations outcome.
With the development and connection of Web services into workflows, however, these large scale datasets can be processed systematically enabling detailed information to be gathered, published and subsequently re-investigated, enhancing the possibility of bridging the gap between genotype and phenotype using pathways.
So far this investigation has highlighted the issues facing the manual analysis of microarray and QTL data, and how automated approaches provide a systematic means to investigate genotype-phenotype correlations. We were able to illustrate how the large scale analysis of microarray gene expression and quantitative trait data, investigated at the level of biological pathways, enables links between genotype and phenotype to be successfully established.
An example of a workflow used to gather pathway information for candidate genes from a QTL region is shown below. These workflows have so far been applied to two different genotype-phenotype problems:
- The study of resistance to African Trypanosomiasis in mice, infected with Trypanosoma congolen
- The study of immunological effects and parasite expulsion in mice infected with Trichuris muris
Using this systematic, pathway driven approach, we were able to successfully identify a candidate gene and biological pathway believed to be strongly associated with resistance to African Trypanosomiasis.
The workflow for performing this analysis is available on myExperiment.
Publications
Articles and papers about the success of Taverna for trypanosomiasis (sleeping sickness) research.
