Pathway Maps of Orphan and Complex Diseases Using an Integrative Computational Approach

Abstract EN

Orphan diseases (ODs) are progressive genetic disorders, which affect a small number of people.

The principal fundamental aspects related to these diseases include insufficient knowledge of mechanisms involved in the physiopathology necessary to access correct diagnosis and to develop appropriate healthcare.

Unlike ODs, complex diseases (CDs) have been widely studied due to their high incidence and prevalence allowing to understand the underlying mechanisms controlling their physiopathology.

Few studies have focused on the relationship between ODs and CDs to identify potential shared pathways and related molecular mechanisms which would allow improving disease diagnosis, prognosis, and treatment.

We have performed a computational approach to studying CDs and ODs relationships through (1) connecting diseases to genes based on genes-diseases associations from public databases, (2) connecting ODs and CDs through binary associations based on common associated genes, and (3) linking ODs and CDs to common enriched pathways.

Among the most shared significant pathways between ODs and CDs, we found pathways in cancer, p53 signaling, mismatch repair, mTOR signaling, B cell receptor signaling, and apoptosis pathways.

Our findings represent a reliable resource that will contribute to identify the relationships between drugs and disease-pathway networks, enabling to optimise patient diagnosis and disease treatment.