Article Spotlight: Dark kinase annotation, mining, and visualization using the Protein Kinase Ontology

by | Mar 6, 2024 | Article Spotlight

Highlighted in the Advances in Illuminating the Druggable Genome Special Issue

The Protein Kinase Ontology (ProKinO) is an integrated knowledge graph that conceptualizes the complex relationships among protein kinase sequence, structure, function, and disease in a human and machine-readable format.

 

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“My lab is focused on the grand challenge of mapping the relationships connecting protein sequence, structure, and function.”
Dr Natarajan Kannan

For All Readers - AI Explainer

What is ProKinO and what does it aim to achieve?

ProKinO stands for Protein Kinase Ontology, which is essentially a structured knowledge graph designed to organize and make sense of various aspects related to protein kinases—important molecules involved in cellular signaling. It aims to integrate information about protein kinase sequences, structures, functions, and their roles in diseases like cancer.

What are the key updates made to ProKinO in this study?

This study significantly expands ProKinO by incorporating additional data on expression patterns and drug interactions. It also introduces a new browser to visualize the knowledge graph on the web. Moreover, ProKinO has been enriched with new classes and relationships, enhancing its capability to uncover insights about less-studied members of the protein kinase family.

How was ProKinO utilized in identifying potential targets in cancer research?

Through graph mining and aggregate SPARQL queries, researchers identified PAK5 (p21-activated protein kinase 5) as one of the most frequently mutated “dark” kinases in human cancers. They found abnormal expression of PAK5 in multiple cancers, including its previously unknown role in acute myeloid leukemia. Recurrent oncogenic mutations in PAK5 were identified, potentially altering its function in substrate binding and phosphorylation.

What implications does the identification of PAK5 have in cancer research and drug discovery?

The discovery of PAK5’s involvement in various cancers, along with recurrent mutations affecting its function, opens new avenues for targeted therapies. Additionally, the identification of common ligand/drug binding residues in PAK family kinases suggests the potential application of ProKinO in drug discovery efforts targeting these kinases.

How accessible is the updated ProKinO database for researchers?

The updated ProKinO database is accessible online at https://prokino.uga.edu. It follows FAIR (Findable, Accessible, Interoperable, and Reusable) principles, ensuring easy accessibility and usability for the scientific community. Moreover, efforts are underway to develop a graphical SPARQL query interface, making it easier for researchers to navigate and utilize the database effectively.

 

 

Dark kinase annotation, mining, and visualization using the Protein Kinase Ontology

 

The Protein Kinase Ontology (ProKinO) is an integrated knowledge graph that conceptualizes the complex relationships among protein kinase sequence, structure, function, and disease in a human and machine-readable format. In this study, we have significantly expanded ProKinO by incorporating additional data on expression patterns and drug interactions.

 

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