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Biology subjects

Poroshin, V.

Publications and source records attributed to Poroshin, V..

2 recordsLinked to original sources

Biological Insights Knowledge Graph: an integrated knowledge graph to support drug development

The use of knowledge graphs as a data source for machine learning methods to solve complex problems in life sciences has rapidly become popular in recent years. Our Biological Insights Knowledge Graph (BIKG) combines relevant data for drug development from public as well as internal data sources to provide insights for a range of tasks: from identifying new targets to repurposing existing drugs. Besides the common requirements to organisational knowledge graphs such as being able to capture the domain precisely and give the users the ability to search and query the data, the focus on handling multiple use cases and supporting use case-specific machine learning models presents additional challenges: the data models must also be streamlined for the performance of downstream tasks; graph content must be easily customisable for different use cases; different projections of the graph content are required to support a wider range of different consumption modes. In this paper we describe our main design choices in implementation of the BIKG graph and discuss different aspects of its life cycle: from graph construction to exploitation.

systems biology↗

Knowledge Graph-based Recommendation Framework Identifies Novel Drivers of Resistance in EGFR mutant Non-small Cell Lung Cancer

Resistance to EGFR inhibitors (EGFRi) presents a major obstacle in treating non-small cell lung cancer (NSCLC). One of the most exciting new ways to find potential resistance markers involves running functional genetic screens, such as CRISPR, followed by manual triage of significantly enriched genes. This triage process to identify high value hits resulting from the CRISPR screen involves significant manual curation that requires specialized knowledge and can take even experts several months to comprehensively complete. To find key drivers of resistance faster we built a hybrid recommendation system on top of a heterogeneous biomedical knowledge graph integrating preclinical, clinical, and literature evidence. Genes were ranked based on trade-offs between diverse types of evidence linking them to potential mechanisms of EGFRi resistance. This unbiased approach identified 36 resistance markers from >3,000 genes, reducing hit identification time from months to minutes. In addition to reproducing known resistance markers, our method identified novel resistance mechanisms that we prospectively validated.

cancer biology↗