KinOrtho

KinOrtho maps human kinase orthologs across the tree of life to elucidate evolutionary relationships and infer functions of understudied protein kinases.

Key Features:

• Query- and graph-based orthology inference: Implements a query- and graph-based orthology inference method for identifying orthologs.
• Full-length and domain-based integration: Integrates full-length and domain-based approaches to combine whole-protein and domain-level orthology evidence.
• Extensive taxonomic coverage: Maps one-to-one kinase orthologs across 17 thousand fully sequenced kinomes.
• False-positive minimization: Flags sequences lacking a proper kinase domain to minimize false positives.
• Domain event detection: Detects domain fusion and evolutionary fission events at the kinase-domain level.
• Function prediction: Integrates Gene Ontology annotations and machine learning to propose putative functions for understudied kinases.
• Curated ortholog sets: Produces well-curated ortholog sets that can be adapted to other gene families.

Scientific Applications:

• Functional inference for understudied kinases: Uses ortholog relationships to propose functions for poorly characterized kinases.
• Domain fusion detection: Identifies domain fusion events such as the reported fusion between TAOK1 and PIK3C2A.
• Evolutionary fission detection: Detects evolutionary fission events including those involving OBSCN kinase domains.
• Annotation transfer and prediction: Supports GO-based and machine-learning-derived predictions including putative roles for TP53RK in cell cycle checkpoints, TSSK3 and TSSK6 in acrosomal vesicle localization, and ULK4 in neuronal development.
• Comparative genomics of kinomes: Enables cross-species comparative analyses across thousands of kinomes to study kinase evolution.

Methodology:

Query- and graph-based orthology inference that integrates full-length and domain-based approaches, flags sequences lacking a kinase domain, and integrates Gene Ontology annotations with machine learning for function prediction.