PsyMuKB: An Integrative De Novo Variant Knowledge Base for Developmental Disorders

Area of Science:

• Genetics
• Neuroscience
• Bioinformatics

Background:

• De novo variants (DNVs) are key drivers of severe early-onset genetic disorders, including autism spectrum disorder and intellectual disability.
• While gene-level impacts of DNVs are studied, isoform-level effects, particularly in the brain's complex splicing landscape, remain underexplored.
• Understanding transcriptional regulation is vital for deciphering mechanisms behind developmental and neuropsychiatric (DNP) disorders.

Purpose of the Study:

• To develop a comprehensive resource for interpreting DNVs at the isoform level.
• To facilitate the identification and functional study of DNVs impacting specific transcript isoforms in DNP disorders.
• To provide an accessible platform for researchers studying genetic contributions to neurodevelopmental conditions.

Main Methods:

• Curated a comprehensive list of DNVs with detailed transcriptional and translational annotations.
• Developed the NeuroPsychiatric Mutation Knowledge Base (PsyMuKB) with a user-friendly web interface.
• Integrated data visualizations including gene expression, transcript structures, protein interactions, and mutation mapping.

Main Results:

• PsyMuKB provides isoform-specific mutation identification and analysis capabilities.
• The knowledge base offers flexible search functions for genes and variants.
• Visualizations aid in understanding mutation locations, characteristics, and expression patterns of affected genes and isoforms.

Conclusions:

• PsyMuKB is a valuable resource for identifying tissue-specific DNVs relevant to DNP disorders.
• The platform facilitates deeper insights into the functional impact of genetic variants at the isoform level.
• Improved interpretation of DNVs through PsyMuKB can advance research into the genetic underpinnings of neurodevelopmental and neuropsychiatric conditions.