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Modular organization of the human disease genes: a text-based network inference.

ABSTRACT: The analysis of disease phenotype data with genetic information indicated that genes associated with clinically similar diseases tend to be functionally related and work together to perform a specific biological function. Therefore, it is of interest to relate disease phenotype data to mirror modular property implied in the association map of disease genes. Hence, we constructed a textbased human disease gene network (HDGN) by using the phenotypic similarity of their associated disease phenotype records in the OMIM database. Analysis shows that the network is highly modular and it is highly correlated with the physiological classification of genetic diseases. Using a graph clustering algorithm, we found 139 gene modules in the network of 1,865 genes and their gene products (proteins) in these gene modules tend to interact with each other via the computation of PPI intensity. Genes in such gene modules are functionally related and may represent the shared genetic basis of their corresponding diseases. These genes, alone or in combination, could be considered as potential therapeutic targets in future clinical therapy.

SUBMITTER: Xuan H

PROVIDER: S-EPMC4620620 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Modular organization of the human disease genes: a text-based network inference.

Xuan Hongdong H Li Xin X Ren Shenrong S Zhang Shihua S

Bioinformation 20150930 9

The analysis of disease phenotype data with genetic information indicated that genes associated with clinically similar diseases tend to be functionally related and work together to perform a specific biological function. Therefore, it is of interest to relate disease phenotype data to mirror modular property implied in the association map of disease genes. Hence, we constructed a textbased human disease gene network (HDGN) by using the phenotypic similarity of their associated disease phenotype ...[more]

PMID: 26527852

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Project description:MotivationOver the past few years, experimental evidence has highlighted the role of microRNAs to human diseases. miRNAs are critical for the regulation of cellular processes, and, therefore, their aberration can be among the triggering causes of pathological phenomena. They are just one member of the large class of non-coding RNAs, which include transcribed ultra-conserved regions (T-UCRs), small nucleolar RNAs (snoRNAs), PIWI-interacting RNAs (piRNAs), large intergenic non-coding RNAs (lincRNAs) and, the heterogeneous group of long non-coding RNAs (lncRNAs). Their associations with diseases are few in number, and their reliability is questionable. In literature, there is only one recent method proposed by Yang et al. (2014) to predict lncRNA-disease associations. This technique, however, lacks in prediction quality. All these elements entail the need to investigate new bioinformatics tools for the prediction of high quality ncRNA-disease associations. Here, we propose a method called ncPred for the inference of novel ncRNA-disease association based on recommendation technique. We represent our knowledge through a tripartite network, whose nodes are ncRNAs, targets, or diseases. Interactions in such a network associate each ncRNA with a disease through its targets. Our algorithm, starting from such a network, computes weights between each ncRNA-disease pair using a multi-level resource transfer technique that at each step takes into account the resource transferred in the previous one.ResultsThe results of our experimental analysis show that our approach is able to predict more biologically significant associations with respect to those obtained by Yang et al. (2014), yielding an improvement in terms of the average area under the ROC curve (AUC). These results prove the ability of our approach to predict biologically significant associations, which could lead to a better understanding of the molecular processes involved in complex diseases.AvailabilityAll the ncPred predictions together with the datasets used for the analysis are available at the following url: http://alpha.dmi.unict.it/ncPred/

Project description:Most complex cognitive tasks require the coordinated interplay of multiple brain networks, but the act of retrieving an episodic memory may place especially heavy demands for communication between the frontoparietal control network (FPCN) and the default mode network (DMN), two networks that do not strongly interact with one another in many task contexts. We applied graph theoretical analysis to task-related fMRI functional connectivity data from 20 human participants and found that global brain modularity-a measure of network segregation-is markedly reduced during episodic memory retrieval relative to closely matched analogical reasoning and visuospatial perception tasks. Individual differences in modularity were correlated with memory task performance, such that lower modularity levels were associated with a lower false alarm rate. Moreover, the FPCN and DMN showed significantly elevated coupling with each other during the memory task, which correlated with the global reduction in brain modularity. Both networks also strengthened their functional connectivity with the hippocampus during the memory task. Together, these results provide a novel demonstration that reduced modularity is conducive to effective episodic retrieval, which requires close collaboration between goal-directed control processes supported by the FPCN and internally oriented self-referential processing supported by the DMN.SIGNIFICANCE STATEMENT Modularity, an index of the degree to which nodes of a complex system are organized into discrete communities, has emerged as an important construct in the characterization of brain connectivity dynamics. We provide novel evidence that the modularity of the human brain is reduced when individuals engage in episodic memory retrieval, relative to other cognitive tasks, and that this state of lower modularity is associated with improved memory performance. We propose a neural systems mechanism for this finding where the nodes of the frontoparietal control network and default mode network strengthen their interaction with one another during episodic retrieval. Such across-network communication likely facilitates effective access to internally generated representations of past event knowledge.

Dataset Information

Modular organization of the human disease genes: a text-based network inference.

Publications

Modular organization of the human disease genes: a text-based network inference.

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