Article detail · 2009
Edgetic perturbation models of human inherited disorders
- Year
- 2009
- Type
- article
Data source split
- YÖKSİS YÖKSİS article record
- YÖKSİS venue Molecular Systems Biology
- Catalog match (ISSN) Molecular Systems Biology
- OpenAlex OpenAlex enrichment (abstract, citations, topics)
Abstract
OpenAlex · English
Cellular functions are mediated through complex systems of macromolecules and metabolites linked through biochemical and physical interactions, represented in interactome models as 'nodes' and 'edges', respectively. Better understanding of genotype-to-phenotype relationships in human disease will require modeling of how disease-causing mutations affect systems or interactome properties. Here we investigate how perturbations of interactome networks may differ between complete loss of gene products ('node removal') and interaction-specific or edge-specific ('edgetic') alterations. Global computational analyses of approximately 50,000 known causative mutations in human Mendelian disorders revealed clear separations of mutations probably corresponding to those of node removal versus edgetic perturbations. Experimental characterization of mutant alleles in various disorders identified diverse edgetic interaction profiles of mutant proteins, which correlated with distinct structural properties of disease proteins and disease mechanisms. Edgetic perturbations seem to confer distinct functional consequences from node removal because a large fraction of cases in which a single gene is linked to multiple disorders can be modeled by distinguishing edgetic network perturbations. Edgetic network perturbation models might improve both the understanding of dissemination of disease alleles in human populations and the development of molecular therapeutic strategies.
Topics
Citations
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370 citations
OpenAlex cited_by_count (cache / database)
9 publications in the local catalog that cite this work (OpenAlex reference match; not the full global list).
- A Proteome-Scale Map of the Human Interactome Network 2014
- Hot spots in protein–protein interfaces: Towards drug discovery 2014
- Combining Structural Modeling with Ensemble Machine Learning to Accurately Predict Protein Fold Stability and Binding Affinity Effects upon Mutation 2014
- Defining clinical subgroups and genotype–phenotype correlations in NBAS-associated disease across 110 patients 2020
- Edgetic perturbation of a C elegans BCL2 ortholog 2009
- A reference map of the human protein interactome 2019
- High Prevalence of Cerebral Venous Sinus Thrombosis CVST as Presentation of Cystathionine Beta Synthase Deficiency in Childhood Molecular and Clinical Findings of Turkish Probands 2014
- High prevalence of cerebral venous sinus thrombosis CVST as presentation of cystathionine beta synthase deficiency in childhood Molecular and clinical findings of Turkish probands 2014
- High prevalence of cerebral venous sinus thrombosis CVST as presentation of cystathionine beta synthase deficiency in childhood Molecular and clinical findings of Turkish probands 2014