Abstract
BackgroundThe pathogenesis of neurological and mental health disorders often involves multiple genes, complex interactions, as well as brain- and development-specific biological mechanisms. These characteristics make identification of disease genes for such disorders challenging, as conventional prioritisation tools are not specifically tailored to deal with the complexity of the human brain. Thus, we developed a novel web-application—brain-coX—that offers gene prioritisation with accompanying visualisations based on seven gene expression datasets in the post-mortem human brain, the largest such resource ever assembled.ResultsWe tested whether our tool can correctly prioritise known genes from 37 brain-specific KEGG pathways and 17 psychiatric conditions. We achieved average sensitivity of nearly 50%, at the same time reaching a specificity of approximately 75%. We also compared brain-coX’s performance to that of its main competitors, Endeavour and ToppGene, focusing on the ability to discover novel associations. Using a subset of the curated SFARI autism gene collection we show that brain-coX’s prioritisations are most similar to SFARI’s own curated gene classifications.Conclusionsbrain-coX is the first prioritisation and visualisation web-tool targeted to the human brain and can be freely accessed via http://shiny.bioinf.wehi.edu.au/freytag.s/.
Highlights
The pathogenesis of neurological and mental health disorders often involves multiple genes, complex interactions, as well as brain- and development-specific biological mechanisms
Very few tools offer both in silico prioritisation and gene network visualisation, which hinders interpretation and design of functional downstream analysis [8]. brain-coX is a novel web-application focusing on gene prioritisation and exploration of gene networks for diseases that originate in human brain tissue
This principle assumes that the most promising candidate genes will be the ones that are associated with genes already known to be involved in the disease. Such candidates are likely to be part of the same biological network(s) that, when disrupted, lead to the development of the disease. The reliance on this principle means that the user is required to supply already known disease genes in order to prioritise their candidate genes
Summary
The pathogenesis of neurological and mental health disorders often involves multiple genes, complex interactions, as well as brain- and development-specific biological mechanisms. Brain-coX is a novel web-application focusing on gene prioritisation and exploration of gene networks for diseases that originate in human brain tissue. Brain-coX allows users to investigate pathway membership and to explore changes in gene networks throughout brain development via interactive visualisations.
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