A network analysis of cofactor-protein interactions for analyzing associations between human nutrition and diseases.

Marie Pier Scott-Boyer,Corrado Priami,Jim Kaput,Melissa J. Morine,Marco Scotti,Sébastien Lacroix

doi:10.1038/srep19633

Abstract

The involvement of vitamins and other micronutrients in intermediary metabolism was elucidated in the mid 1900’s at the level of individual biochemical reactions. Biochemical pathways remain the foundational knowledgebase for understanding how micronutrient adequacy modulates health in all life stages. Current daily recommended intakes were usually established on the basis of the association of a single nutrient to a single, most sensitive adverse effect and thus neglect interdependent and pleiotropic effects of micronutrients on biological systems. Hence, the understanding of the impact of overt or sub-clinical nutrient deficiencies on biological processes remains incomplete. Developing a more complete view of the role of micronutrients and their metabolic products in protein-mediated reactions is of importance. We thus integrated and represented cofactor-protein interaction data from multiple and diverse sources into a multi-layer network representation that links cofactors, cofactor-interacting proteins, biological processes, and diseases. Network representation of this information is a key feature of the present analysis and enables the integration of data from individual biochemical reactions and protein-protein interactions into a systems view, which may guide strategies for targeted nutritional interventions aimed at improving health and preventing diseases.

Highlights

Comprehensive databases linking multiple interactions of micronutrient and components to biological pathways and diseases are not available
The resulting network representation of cofactor-protein interactions can be found in Fig. 2 where cofactor-interacting proteins were linked to their required cofactors
A century of research focusing on individual reactions and related pathways has produced detailed biochemical maps of intermediary metabolism

Summary

Introduction

Comprehensive databases linking multiple interactions of micronutrient (as cofactors) and components (proteins) to biological pathways and diseases are not available. To address this knowledge gap, data from multiple sources was integrated to create a comprehensive knowledgebase of cofactors, their protein interactions, and associated diseases. This dataset was represented as an integrative multi-layered network linking cofactors, cofactor-interacting proteins, biological processes, and diseases (Fig. 1). The integrative network analysis presented here aids in unraveling how micronutrient (in)adequacies can influence multiple biological processes, leading to health maintenance or disease progression

Methods

Results

Conclusion