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A survey of protein interaction data and multigenic inherited disorders.

ABSTRACT: BACKGROUND: Multigenic diseases are often associated with protein complexes or interactions involved in the same pathway. We wanted to estimate to what extent this is true given a consolidated protein interaction data set. The study stresses data integration and data representation issues. RESULTS: We constructed 497 multigenic disease groups from OMIM and tested for overlaps with interaction and pathway data. A total of 159 disease groups had significant overlaps with protein interaction data consolidated by iRefIndex. A further 68 disease overlaps were found only in the KEGG pathway database. No single database contained all significant overlaps thus stressing the importance of data integration. We also found that disease groups overlapped with all three interaction data types: n-ary, spoke-represented complexes and binary data - thus stressing the importance of considering each of these data types separately. CONCLUSIONS: Almost half of our multigenic disease groups could potentially be explained by protein complexes and pathways. However, the fact that no database or data type was able to cover all disease groups suggests that no single database has systematically covered all disease groups for potential related complex and pathway data. This survey provides a basis for further curation efforts to confirm and search for overlaps between diseases and interaction data. The accompanying R script can be used to reproduce the work and track progress in this area as databases change. Disease group overlaps can be further explored using the iRefscape plugin for Cytoscape.

SUBMITTER: Mora A

PROVIDER: S-EPMC3598893 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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A survey of protein interaction data and multigenic inherited disorders.

Mora Antonio A Michalickova Katerina K Donaldson Ian M IM

BMC bioinformatics 20130211

<h4>Background</h4>Multigenic diseases are often associated with protein complexes or interactions involved in the same pathway. We wanted to estimate to what extent this is true given a consolidated protein interaction data set. The study stresses data integration and data representation issues.<h4>Results</h4>We constructed 497 multigenic disease groups from OMIM and tested for overlaps with interaction and pathway data. A total of 159 disease groups had significant overlaps with protein inter ...[more]

PMID: 23398688

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Project description:Hereditary iron overload includes several disorders characterized by iron accumulation in tissues, organs, or even single cells or subcellular compartments. They are determined by mutations in genes directly involved in hepcidin regulation, cellular iron uptake, management and export, iron transport and storage. Systemic forms are characterized by increased serum ferritin with or without high transferrin saturation, and with or without functional iron deficient anemia. Hemochromatosis includes five different genetic forms all characterized by high transferrin saturation and serum ferritin, but with different penetrance and expression. Mutations in HFE, HFE2, HAMP and TFR2 lead to inadequate or severely reduced hepcidin synthesis that, in turn, induces increased intestinal iron absorption and macrophage iron release leading to tissue iron overload. The severity of hepcidin down-regulation defines the severity of iron overload and clinical complications. Hemochromatosis type 4 is caused by dominant gain-of-function mutations of ferroportin preventing hepcidin-ferroportin binding and leading to hepcidin resistance. Ferroportin disease is due to loss-of-function mutation of SLC40A1 that impairs the iron export efficiency of ferroportin, causes iron retention in reticuloendothelial cell and hyperferritinemia with normal transferrin saturation. Aceruloplasminemia is caused by defective iron release from storage and lead to mild microcytic anemia, low serum iron, and iron retention in several organs including the brain, causing severe neurological manifestations. Atransferrinemia and DMT1 deficiency are characterized by iron deficient erythropoiesis, severe microcytic anemia with high transferrin saturation and parenchymal iron overload due to secondary hepcidin suppression. Diagnosis of the different forms of hereditary iron overload disorders involves a sequential strategy that combines clinical, imaging, biochemical, and genetic data. Management of iron overload relies on two main therapies: blood removal and iron chelators. Specific therapeutic options are indicated in patients with atransferrinemia, DMT1 deficiency and aceruloplasminemia.

Dataset Information

A survey of protein interaction data and multigenic inherited disorders.

Publications

A survey of protein interaction data and multigenic inherited disorders.

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