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Towards systems biology of human pulmonary fibrosis.

ABSTRACT: The integrated effect of multiple pathways, molecules, genetic polymorphisms, environmental stimuli, and possible infection determines the lung phenotype in idiopathic pulmonary fibrosis (IPF), a chronic progressive and often lethal lung disease. Systems biology approaches aim to provide a systemwide view of biological process using computational tools and high-throughput technologies. Although much of the analysis of genome-level transcriptional high-resolution profiles of IPF was reductionist, usually focusing on a single factor in the disease process, there are some studies that implement systems approaches. We discuss these analyses and provide examples of the global analysis of IPF, hypersensitivity pneumonitis, and nonspecific interstitial pneumonia. Detailed quantitative phenotyping and correlation with microarray results as well as high-throughput genotyping should provide us with the datasets to implement systems biology approaches in fibrosis research. Interdisciplinary teams and training of junior investigators in the vocabulary of systems biology should allow us to use these datasets integratively and generate a global model of human pulmonary fibrosis.

SUBMITTER: Studer SM

PROVIDER: S-EPMC2647618 | biostudies-literature | 2007 Jan

REPOSITORIES: biostudies-literature

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Towards systems biology of human pulmonary fibrosis.

Studer Sean M SM Kaminski Naftali N

Proceedings of the American Thoracic Society 20070101 1

The integrated effect of multiple pathways, molecules, genetic polymorphisms, environmental stimuli, and possible infection determines the lung phenotype in idiopathic pulmonary fibrosis (IPF), a chronic progressive and often lethal lung disease. Systems biology approaches aim to provide a systemwide view of biological process using computational tools and high-throughput technologies. Although much of the analysis of genome-level transcriptional high-resolution profiles of IPF was reductionist, ...[more]

PMID: 17202296

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Project description:BackgroundComprehensive understanding of molecular mechanisms underlying viral infection is a major challenge towards the discovery of new antiviral drugs and susceptibility factors of human diseases. New advances in the field are expected from systems-level modelling and integration of the incessant torrent of high-throughput "-omics" data.ResultsHere, we describe the Human Infectome protein interaction Network, a novel systems virology model of a virtual virus-infected human cell concerning 110 viruses. This in silico model was applied to comprehensively explore the molecular relationships between viruses and their associated diseases. This was done by merging virus-host and host-host physical protein-protein interactomes with the set of genes essential for viral replication and involved in human genetic diseases. This systems-level approach provides strong evidence that viral proteomes target a wide range of functional and inter-connected modules of proteins as well as highly central and bridging proteins within the human interactome. The high centrality of targeted proteins was correlated to their essentiality for viruses' lifecycle, using functional genomic RNAi data. A stealth-attack of viruses on proteins bridging cellular functions was demonstrated by simulation of cellular network perturbations, a property that could be essential in the molecular aetiology of some human diseases. Networking the Human Infectome and Diseasome unravels the connectivity of viruses to a wide range of diseases and profiled molecular basis of Hepatitis C Virus-induced diseases as well as 38 new candidate genetic predisposition factors involved in type 1 diabetes mellitus.ConclusionsThe Human Infectome and Diseasome Networks described here provide a unique gateway towards the comprehensive modelling and analysis of the systems level properties associated to viral infection as well as candidate genes potentially involved in the molecular aetiology of human diseases.

Dataset Information

Towards systems biology of human pulmonary fibrosis.

Publications

Towards systems biology of human pulmonary fibrosis.

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