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The translational network for metabolic disease - from protein interaction to disease co-occurrence.

ABSTRACT: BACKGROUND:The recent advances in human disease network have provided insights into establishing the relationships between the genotypes and phenotypes of diseases. In spite of the great progress, it yet remains as only a map of topologies between diseases, but not being able to be a pragmatic diagnostic/prognostic tool in medicine. It can further evolve from a map to a translational tool if it equips with a function of scoring that measures the likelihoods of the association between diseases. Then, a physician, when practicing on a patient, can suggest several diseases that are highly likely to co-occur with a primary disease according to the scores. In this study, we propose a method of implementing 'n-of-1 utility' (n potential diseases of one patient) to human disease network-the translational disease network. RESULTS:We first construct a disease network by introducing the notion of walk in graph theory to protein-protein interaction network, and then provide a scoring algorithm quantifying the likelihoods of disease co-occurrence given a primary disease. Metabolic diseases, that are highly prevalent but have found only a few associations in previous studies, are chosen as entries of the network. CONCLUSIONS:The proposed method substantially increased connectivity between metabolic diseases and provided scores of co-occurring diseases. The increase in connectivity turned the disease network info-richer. The result lifted the AUC of random guessing up to 0.72 and appeared to be concordant with the existing literatures on disease comorbidity.

SUBMITTER: Nam Y

PROVIDER: S-EPMC6854734 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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The translational network for metabolic disease - from protein interaction to disease co-occurrence.

Nam Yonghyun Y Lee Dong-Gi DG Bang Sunjoo S Kim Ju Han JH Kim Jae-Hoon JH Shin Hyunjung H

BMC bioinformatics 20191113 1

<h4>Background</h4>The recent advances in human disease network have provided insights into establishing the relationships between the genotypes and phenotypes of diseases. In spite of the great progress, it yet remains as only a map of topologies between diseases, but not being able to be a pragmatic diagnostic/prognostic tool in medicine. It can further evolve from a map to a translational tool if it equips with a function of scoring that measures the likelihoods of the association between dis ...[more]

PMID: 31722666

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Project description:Dynamic protein-protein interactions control cellular behavior, from motility to DNA replication to signal transduction. However, monitoring dynamic interactions among multiple proteins in a protein interaction network is technically difficult. Here, we present a protocol for Quantitative Multiplex Immunoprecipitation (QMI), which allows quantitative assessment of fold changes in protein interactions based on relative fluorescence measurements of Proteins in Shared Complexes detected by Exposed Surface epitopes (PiSCES). In QMI, protein complexes from cell lysates are immunoprecipitated onto microspheres, and then probed with a labeled antibody for a different protein in order to quantify the abundance of PiSCES. Immunoprecipitation antibodies are conjugated to different MagBead spectral regions, which allows a flow cytometer to differentiate multiple parallel immunoprecipitations and simultaneously quantify the amount of probe antibody associated with each. QMI does not require genetic tagging and can be performed using minimal biomaterial compared to other immunoprecipitation methods. QMI can be adapted for any defined group of interacting proteins, and has thus far been used to characterize signaling networks in T cells and neuronal glutamate synapses. Results have led to new hypothesis generation with potential diagnostic and therapeutic applications. This protocol includes instructions to perform QMI, from the initial antibody panel selection through to running assays and analyzing data. The initial assembly of a QMI assay involves screening antibodies to generate a panel, and empirically determining an appropriate lysis buffer. The subsequent reagent preparation includes covalently coupling immunoprecipitation antibodies to MagBeads, and biotinylating probe antibodies so they can be labeled by a streptavidin-conjugated fluorophore. To run the assay, lysate is mixed with MagBeads overnight, and then beads are divided and incubated with different probe antibodies, and then a fluorophore label, and read by flow cytometry. Two statistical tests are performed to identify PiSCES that differ significantly between experimental conditions, and results are visualized using heatmaps or node-edge diagrams.

Dataset Information

The translational network for metabolic disease - from protein interaction to disease co-occurrence.

Publications

The translational network for metabolic disease - from protein interaction to disease co-occurrence.

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