Origin and Consequences of Phenotype-Associated Biological Network Changes

About this Research Topic

Background

Networks in biology are derived from the interactions between genes, transcripts, proteins, and metabolites: protein-protein interactions (PPIs), gene-regulatory and metabolic networks. Phenotypic changes are caused by perturbations of the products of multiple genes from various biological processes that act cooperatively to mediate the phenotype. The underlying premise to associate protein interactions with diseases is that phenotypic variations resulting in human disease arise from perturbations of cellular interactome networks produced by the loss or gain of function mutations in a set of gene products and, in consequence, the loss or gain of some of its interactions. The latter are also referred to as edgetic perturbations.

Network biology has proven its use in identifying candidate disease genes based on the simple but significant observation that proteins of phenotypically related genes tend to interact with each other or be close to each other in cellular networks. Nevertheless, due to the inherent complexity of most phenotypes, to comprehend their underlying mechanisms requires taking into account information on sequence variation, gene regulators and their effects at the level of the system (e.g. pathways, metabolic networks, etc). Therefore, studying dysregulation patterns of the protein interaction and regulatory networks is key to delineate disease related pathways in a systemic view.

Deepening on the molecular mechanisms, the structural characterization of PPIs helps us understand the causes of the rewiring in a healthy network resulting in a phenotype. We invite submissions of reviews, perspectives, original research articles, and applications to this research topic that cover but are not limited to any of the following subjects:

• Structural studies of mutations and how they rewire molecular interaction networks
• System-wide analyses of biological network rewiring in a phenotypic context
• Prediction of network perturbations in a disease context
• Experimental investigations of network perturbations when combined with theoretical or bioinformatic work
• Bioinformatic studies of disease-associated rewiring of any type of molecular or biological network
• Network rewiring as a consequence of changes in post-translational modifications in a phenotypic context
• Residue networks in proteins
• If you are not sure whether your research fits to the scope of this Research Topic, please, contact the editors.

Homepage picture from Rachael Arnott.

Keywords: Biological Network Rewiring, Interactome, Disease, Molecular Network Changes Mutations, Genetic variations, Differential Network Analysis, Conditional Networks

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