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Comparative analysis of protein interaction networks reveals that conserved pathways are susceptible to HIV-1 interception.

Qian X, Yoon BJ - BMC Bioinformatics (2011)

Bottom Line: Our analysis shows that the conserved pathways have a significantly higher probability of being intercepted by HIV-1.We expect that comparative multiple network analysis of various species that have different levels of susceptibility to similar lentiviruses may provide a very effective framework for generating novel, and experimentally verifiable hypotheses on the mechanisms of HIV-1.We believe that the proposed framework has the potential to expedite the elucidation of the important mechanisms of HIV-1, and ultimately, the discovery of novel anti-HIV drugs.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Computer Science and Engineering, University of South Florida, Tampa, FL, USA. xqian@cse.usf.edu

ABSTRACT

Background: Human immunodeficiency virus type one (HIV-1) is the major pathogen that causes the acquired immune deficiency syndrome (AIDS). With the availability of large-scale protein-protein interaction (PPI) measurements, comparative network analysis can provide a promising way to study the host-virus interactions and their functional significance in the pathogenesis of AIDS. Until now, there have been a large number of HIV studies based on various animal models. In this paper, we present a novel framework for studying the host-HIV interactions through comparative network analysis across different species.

Results: Based on the proposed framework, we test our hypothesis that HIV-1 attacks essential biological pathways that are conserved across species. We selected the Homo sapiens and Mus musculus PPI networks with the largest coverage among the PPI networks that are available from public databases. By using a local network alignment algorithm based on hidden Markov models (HMMs), we first identified the pathways that are conserved in both networks. Next, we analyzed the HIV-1 susceptibility of these pathways, in comparison with random pathways in the human PPI network. Our analysis shows that the conserved pathways have a significantly higher probability of being intercepted by HIV-1. Furthermore, Gene Ontology (GO) enrichment analysis shows that most of the enriched GO terms are related to signal transduction, which has been conjectured to be one of the major mechanisms targeted by HIV-1 for the takeover of the host cell.

Conclusions: This proof-of-concept study clearly shows that the comparative analysis of PPI networks across different species can provide important insights into the host-HIV interactions and the detailed mechanisms of HIV-1. We expect that comparative multiple network analysis of various species that have different levels of susceptibility to similar lentiviruses may provide a very effective framework for generating novel, and experimentally verifiable hypotheses on the mechanisms of HIV-1. We believe that the proposed framework has the potential to expedite the elucidation of the important mechanisms of HIV-1, and ultimately, the discovery of novel anti-HIV drugs.

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The number of proteins that interact with HIV-1 proteins in conserved pathways (with no gaps) and randomly extracted pathways. (A) The histograms for pathways of size L = 16. (B) The histograms for pathways of size L = 32. (C) The histograms for pathways of size L = 64.
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Figure 2: The number of proteins that interact with HIV-1 proteins in conserved pathways (with no gaps) and randomly extracted pathways. (A) The histograms for pathways of size L = 16. (B) The histograms for pathways of size L = 32. (C) The histograms for pathways of size L = 64.

Mentions: Based on the identified conserved pathways and the randomly extracted pathways, we first computed how many proteins within each pathway can be intercepted by HIV-1, by mapping the predicted human/HIV-1 interactions in [12] onto these pathways. Figure 2 shows the histogram of the number of HIV-1 interacting proteins in conserved pathways as well as the histogram for random pathways. From the figure, there is a clear distinction between the two types of histograms. Typically, the separation between the two histograms increases with the length of the pathways. We can clearly see that highly conserved pathways are more susceptible to HIV-1 interception, in general.


Comparative analysis of protein interaction networks reveals that conserved pathways are susceptible to HIV-1 interception.

Qian X, Yoon BJ - BMC Bioinformatics (2011)

The number of proteins that interact with HIV-1 proteins in conserved pathways (with no gaps) and randomly extracted pathways. (A) The histograms for pathways of size L = 16. (B) The histograms for pathways of size L = 32. (C) The histograms for pathways of size L = 64.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3044273&req=5

Figure 2: The number of proteins that interact with HIV-1 proteins in conserved pathways (with no gaps) and randomly extracted pathways. (A) The histograms for pathways of size L = 16. (B) The histograms for pathways of size L = 32. (C) The histograms for pathways of size L = 64.
Mentions: Based on the identified conserved pathways and the randomly extracted pathways, we first computed how many proteins within each pathway can be intercepted by HIV-1, by mapping the predicted human/HIV-1 interactions in [12] onto these pathways. Figure 2 shows the histogram of the number of HIV-1 interacting proteins in conserved pathways as well as the histogram for random pathways. From the figure, there is a clear distinction between the two types of histograms. Typically, the separation between the two histograms increases with the length of the pathways. We can clearly see that highly conserved pathways are more susceptible to HIV-1 interception, in general.

Bottom Line: Our analysis shows that the conserved pathways have a significantly higher probability of being intercepted by HIV-1.We expect that comparative multiple network analysis of various species that have different levels of susceptibility to similar lentiviruses may provide a very effective framework for generating novel, and experimentally verifiable hypotheses on the mechanisms of HIV-1.We believe that the proposed framework has the potential to expedite the elucidation of the important mechanisms of HIV-1, and ultimately, the discovery of novel anti-HIV drugs.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Computer Science and Engineering, University of South Florida, Tampa, FL, USA. xqian@cse.usf.edu

ABSTRACT

Background: Human immunodeficiency virus type one (HIV-1) is the major pathogen that causes the acquired immune deficiency syndrome (AIDS). With the availability of large-scale protein-protein interaction (PPI) measurements, comparative network analysis can provide a promising way to study the host-virus interactions and their functional significance in the pathogenesis of AIDS. Until now, there have been a large number of HIV studies based on various animal models. In this paper, we present a novel framework for studying the host-HIV interactions through comparative network analysis across different species.

Results: Based on the proposed framework, we test our hypothesis that HIV-1 attacks essential biological pathways that are conserved across species. We selected the Homo sapiens and Mus musculus PPI networks with the largest coverage among the PPI networks that are available from public databases. By using a local network alignment algorithm based on hidden Markov models (HMMs), we first identified the pathways that are conserved in both networks. Next, we analyzed the HIV-1 susceptibility of these pathways, in comparison with random pathways in the human PPI network. Our analysis shows that the conserved pathways have a significantly higher probability of being intercepted by HIV-1. Furthermore, Gene Ontology (GO) enrichment analysis shows that most of the enriched GO terms are related to signal transduction, which has been conjectured to be one of the major mechanisms targeted by HIV-1 for the takeover of the host cell.

Conclusions: This proof-of-concept study clearly shows that the comparative analysis of PPI networks across different species can provide important insights into the host-HIV interactions and the detailed mechanisms of HIV-1. We expect that comparative multiple network analysis of various species that have different levels of susceptibility to similar lentiviruses may provide a very effective framework for generating novel, and experimentally verifiable hypotheses on the mechanisms of HIV-1. We believe that the proposed framework has the potential to expedite the elucidation of the important mechanisms of HIV-1, and ultimately, the discovery of novel anti-HIV drugs.

Show MeSH
Related in: MedlinePlus