Functional Networks of Highest-Connected Splice Isoforms: From The Chromosome 17 Human Proteome Project

Area of Science:

• Genomics
• Proteomics
• Bioinformatics

Background:

• Alternative splicing generates diverse protein isoforms with varied functions.
• Identifying canonical isoforms is crucial for understanding gene and protein roles.
• Previous methods for identifying major isoforms relied on expression or evolutionary traits.

Purpose of the Study:

• To identify and characterize highest connected isoforms (HCIs) in humans.
• To explore the differential expression and conservation of HCIs.
• To provide a resource for studying isoform functional relationships.

Main Methods:

• Constructed a human isoform functional network by integrating genomic data.
• Identified HCIs based on network connectivity.
• Analyzed differential expression using RNA-seq data.
• Validated protein expression using proteomic data.

Main Results:

• Identified HCIs for 6157 multi-isoform human genes.
• Found significantly higher transcript-level expression for HCIs compared to non-HCIs in humans.
• Demonstrated that HCIs are indicators of expressed protein isoforms.
• Observed conservation of HCIs between human and mouse.

Conclusions:

• HCIs represent a novel class of canonical isoforms with distinct expression and functional properties.
• The identified HCIs are valuable for studying main protein products and gene regulation.
• The developed network resource facilitates research into isoform functional relationships and evolution.