Determining Associations between Human Diseases and non-coding RNAs with Critical Roles in Network Control

Area of Science:

• Systems biology
• Genomics
• RNA biology

Background:

• The human genome is extensively transcribed, producing numerous non-protein-coding RNAs (ncRNAs) with regulatory roles.
• Emerging evidence indicates diseases are linked to factors beyond protein-coding gene mutations.

Purpose of the Study:

• To investigate if ncRNAs crucial for biological network control are associated with human diseases.
• To explore the role of ncRNAs in disease etiology.

Main Methods:

• Mapped 350+ human disorders to a large dataset of ncRNA-protein interactions (93,000+ interactions).
• Applied a novel algorithmic controllability framework to a constructed bipartite network.
• Utilized statistical analysis to assess the link between network-critical ncRNAs and diseases.

Main Results:

• ncRNAs involved in critical network control are statistically enriched among disease-associated ncRNAs (P = 9.8 × 10(-109)).
• Identified a significant association between network controllability and disease linkage for ncRNAs.

Conclusions:

• ncRNAs playing key roles in biological networks are significantly linked to human disorders.
• Incorporating ncRNAs involved in critical control can enhance disease gene prioritization efforts.