PhyloSofS

PhyloSofS reconstructs phylogenetic relationships among transcript isoforms and models their protein tertiary structures to study the evolutionary origins and structural consequences of alternative splicing.

Key Features:

• Evolutionary Reconstruction: Reconstructs the evolutionary history of transcripts by generating phylogenetic forests that relate multiple transcript isoforms across species, enabling tracing of alternative splicing event origins within gene families.
• Structural Modeling: Models three-dimensional structures of protein isoforms derived from transcripts to assess effects of structural variation on protein function and stability.
• Automated Analysis: Automates reconstruction of transcript evolutionary scenarios and structural modeling using computational algorithms.
• Application to JNK Family: Reconstructed phylogenetic relationships among 60 protein-coding transcripts observed in seven species and identified two ancient alternative splicing events with subtle effects on protein structural dynamics.
• Identification of Unique Isoforms: Identifies previously uncharacterized transcripts with stably predicted structures and orphan transcripts exhibiting unique sequence and structural properties.

Scientific Applications:

• Proteomics: Provides structural models of isoforms to support analysis of protein structure–function relationships in proteomic studies.
• Evolutionary Biology: Enables tracing the origins of alternative splicing events and comparative analysis of isoform evolution across species.
• Molecular Genetics: Aids investigation of how alternative splicing contributes to functional diversity within gene families such as JNK.
• Disease Mechanism Studies: Supports exploration of mechanistic links between alternative splicing, isoform structure, and disease-related functional changes.

Methodology:

Integrates phylogenetic analysis with structural modeling, using computational algorithms to reconstruct evolutionary scenarios and predict the tertiary structures of isoforms.