Dataset Information

Heterogeneous Network Model to Identify Potential Associations Between Plasmodium vivax and Human Proteins.

ABSTRACT: Integration of multiple sources and data levels provides a great insight into the complex associations between human and malaria systems. In this study, a meta-analysis framework was developed based on a heterogeneous network model for integrating human-malaria protein similarities, a human protein interaction network, and a Plasmodium vivax protein interaction network. An iterative network propagation was performed on the heterogeneous network until we obtained stabilized weights. The association scores were calculated for qualifying a novel potential human-malaria protein association. This method provided a better performance compared to random experiments. After that, the stabilized network was clustered into association modules. The potential association candidates were then thoroughly analyzed by statistical enrichment analysis with protein complexes and known drug targets. The most promising target proteins were the succinate dehydrogenase protein complex in the human citrate (TCA) cycle pathway and the nicotinic acetylcholine receptor in the human central nervous system. Promising associations and potential drug targets were also provided for further studies and designs in therapeutic approaches for malaria at a systematic level. In conclusion, this method is efficient to identify new human-malaria protein associations and can be generalized to infer other types of association studies to further advance biomedical science.

SUBMITTER: Suratanee A

PROVIDER: S-EPMC7072978 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Heterogeneous Network Model to Identify Potential Associations Between <i>Plasmodium vivax</i> and Human Proteins.

Suratanee Apichat A Plaimas Kitiporn K

International journal of molecular sciences 20200215 4

Integration of multiple sources and data levels provides a great insight into the complex associations between human and malaria systems. In this study, a meta-analysis framework was developed based on a heterogeneous network model for integrating human-malaria protein similarities, a human protein interaction network, and a <i>Plasmodium vivax</i> protein interaction network. An iterative network propagation was performed on the heterogeneous network until we obtained stabilized weights. The as ...[more]

PMID: 32075230

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Project description:MicroRNAs (miRNAs) are closely associated with the occurrences and developments of many complex human diseases. Increasing studies have shown that miRNAs emerge as new therapeutic targets of small molecule (SM) drugs. Since traditional experiment methods are expensive and time consuming, it is particularly crucial to find efficient computational approaches to predict potential small molecule-miRNA (SM-miRNA) associations. Considering that integrating multi-source heterogeneous information related with SM-miRNA association prediction would provide a comprehensive insight into the features of both SMs and miRNAs, we proposed a novel model of Small Molecule-MiRNA Association prediction based on Heterogeneous Network Representation Learning (SMMA-HNRL) for more precisely predicting the potential SM-miRNA associations. In SMMA-HNRL, a novel heterogeneous information network was constructed with SM nodes, miRNA nodes and disease nodes. To access and utilize of the topological information of the heterogeneous information network, feature vectors of SM and miRNA nodes were obtained by two different heterogeneous network representation learning algorithms (HeGAN and HIN2Vec) respectively and merged with connect operation. Finally, LightGBM was chosen as the classifier of SMMA-HNRL for predicting potential SM-miRNA associations. The 10-fold cross validations were conducted to evaluate the prediction performance of SMMA-HNRL, it achieved an area under of ROC curve of 0.9875, which was superior to other three state-of-the-art models. With two independent validation datasets, the test experiment results revealed the robustness of our model. Moreover, three case studies were performed. As a result, 35, 37, and 22 miRNAs among the top 50 predicting miRNAs associated with 5-FU, cisplatin, and imatinib were validated by experimental literature works respectively, which confirmed the effectiveness of SMMA-HNRL. The source code and experimental data of SMMA-HNRL are available at https://github.com/SMMA-HNRL/SMMA-HNRL.

Project description:BackgroundHyperbilirubinaemia (bilirubin >51.3 μmol/L) alone is not indicative of severe malaria, and the immune response underlying hyperbilirubinaemia remains largely unexplored. Liver damage associated with hyperbilirubinaemia may alter the expression of hepcidin, which regulates systemic iron by degrading ferroportin. For this study, the association between hepcidin and the levels of cytokines and chemokines in the serum of individuals with mild and severe vivax malaria and subjects with malaria with isolated hyperbilirubinaemia was evaluated.MethodsCytokines/chemokines and hepcidin were measured in individuals with mild (n = 72) and severe (n = 17) vivax malaria, as well as in the serum of subjects with vivax malaria with isolated hyperbilirubinaemia (n = 14) from the Brazilian Amazon between 2009 and 2013 by multiplex assay and ELISA, respectively. The polymorphism 744 G > T in the ferroportin gene was identified by restriction fragment-length polymorphism analysis and the restriction enzyme PvuII.ResultsThe polymorphism at position 744 G > T in the ferroportin gene was typed and no differences in the distributions of genotypes or alleles were observed between the study groups. Subjects with severe malaria had higher levels of interleukin (IL)-2 and IL-13 than subjects with hyperbilirubinaemia. No differences in the expression of immune markers were observed between subjects with mild malaria and those with hyperbilirubinaemia. However, hepcidin levels were higher in individuals with severe malaria and hyperbilirubinaemia than those with mild malaria (p = 0.0002 and p = 0.0004, respectively) and cut-off values of hepcidin differentiated these groups from subjects with mild malaria. Hepcidin was positively associated with IL-6 and IL-10 levels and with parasitaemia in subjects with mild malaria and with IFN-γ in subjects with severe malaria.ConclusionsMalaria in the presence of hyperbilirubinaemia produces a less robust inflammatory response compared to severe cases of malaria. Hepcidin levels are positively associated with immune markers in vivax malaria outcomes.

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Dataset Information

Heterogeneous Network Model to Identify Potential Associations Between Plasmodium vivax and Human Proteins.

Publications

Heterogeneous Network Model to Identify Potential Associations Between <i>Plasmodium vivax</i> and Human Proteins.

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