brain-coX: investigating and visualising gene co-expression in seven human brain transcriptomic datasets

Area of Science:

• Neuroscience
• Genetics
• Bioinformatics

Background:

• Neurological and mental health disorders involve complex genetic and biological mechanisms specific to the brain.
• Identifying disease genes for these disorders is challenging due to the complexity of the human brain.
• Existing prioritization tools are not optimized for brain-specific complexities.

Purpose of the Study:

• To develop a novel web application, brain-coX, for gene prioritization in neurological and mental health disorders.
• To leverage large-scale human brain gene expression datasets for enhanced gene discovery.
• To provide accompanying visualizations for prioritized genes.

Main Methods:

• Developed brain-coX, a web-based gene prioritization tool.
• Utilized seven post-mortem human brain gene expression datasets, the largest assembly to date.
• Integrated gene prioritization with accompanying visualizations.

Main Results:

• brain-coX demonstrated an average sensitivity of nearly 50% and specificity of approximately 75% in prioritizing known genes for brain-specific pathways and psychiatric conditions.
• Comparison with competitors Endeavour and ToppGene showed brain-coX's strength in discovering novel associations.
• Prioritizations by brain-coX closely aligned with the SFARI autism gene collection classifications.

Conclusions:

• brain-coX is the first web-based prioritization and visualization tool specifically designed for the human brain.
• The tool aids in identifying genes associated with neurological and mental health disorders.
• brain-coX is freely accessible for researchers at http://shiny.bioinf.wehi.edu.au/freytag.s/.