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Domain analysis of symbionts and hosts (DASH) in a genome-wide survey of pathogenic human viruses.

Gonzalez MW, Spouge JL - BMC Res Notes (2013)

Bottom Line: Yet, pairwise-sequence searches have limited sensitivity resulting in poor identification of divergent homologies.Our results indicate that HHV-8 shares at least 29% of its genes with humans (fourteen immunomodulatory and ten metabolic genes).Our results validate our approach, showing that DASH has potential as a pipeline for making therapeutic discoveries in other host-symbiont systems.

View Article: PubMed Central - HTML - PubMed

Affiliation: National Institutes of Health, National Library of Medicine, National Center for Biotechnology Information, 8600 Rockville Pike, Building 38A, Room 6N611-M, Bethesda, MD 20894, USA. mileidywgonzalez@gmail.com

ABSTRACT

Background: In the coevolution of viruses and their hosts, viruses often capture host genes, gaining advantageous functions (e.g. immune system control). Identifying functional similarities shared by viruses and their hosts can help decipher mechanisms of pathogenesis and accelerate virus-targeted drug and vaccine development. Cellular homologs in viruses are usually documented using pairwise-sequence comparison methods. Yet, pairwise-sequence searches have limited sensitivity resulting in poor identification of divergent homologies.

Results: Methods based on profiles from multiple sequences provide a more sensitive alternative to identify similarities in host-pathogen systems. The present work describes a profile-based bioinformatics pipeline that we call the Domain Analysis of Symbionts and Hosts (DASH). DASH provides a web platform for the functional analysis of viral and host genomes. This study uses Human Herpesvirus 8 (HHV-8) as a model to validate the methodology. Our results indicate that HHV-8 shares at least 29% of its genes with humans (fourteen immunomodulatory and ten metabolic genes). DASH also suggests functions for fifty-one additional HHV-8 structural and metabolic proteins. We also perform two other comparative genomics studies of human viruses: (1) a broad survey of eleven viruses of disparate sizes and transcription strategies; and (2) a closer examination of forty-one viruses of the order Mononegavirales. In the survey, DASH detects human homologs in 4/5 DNA viruses. None of the non-retro-transcribing RNA viruses in the survey showed evidence of homology to humans. The order Mononegavirales are also non-retro-transcribing RNA viruses, however, and DASH found homology in 39/41 of them. Mononegaviruses display larger fractions of human similarities (up to 75%) than any of the other RNA or DNA viruses (up to 55% and 29% respectively).

Conclusions: We conclude that gene sharing probably occurs between humans and both DNA and RNA viruses, in viral genomes of differing sizes, regardless of transcription strategies. Our method (DASH) simultaneously analyzes the genomes of two interacting species thereby mining functional information to identify shared as well as exclusive domains to each organism. Our results validate our approach, showing that DASH has potential as a pipeline for making therapeutic discoveries in other host-symbiont systems. DASH results are available at http://tinyurl.com/spouge-dash.

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Functional domains shared by humans and forty-one RNA non-retro-transcribing viruses. A species tree of the order Mononegavirales from the NCBI taxonomy. Colored dots on the tree show the mononegaviruses with homologous domains in human. The lower left-hand side of the diagram maps colors to functional domains in the form of [color]/[PfamA accession]/[functional domain description]/[number of mononegaviruses showing given function].
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Figure 3: Functional domains shared by humans and forty-one RNA non-retro-transcribing viruses. A species tree of the order Mononegavirales from the NCBI taxonomy. Colored dots on the tree show the mononegaviruses with homologous domains in human. The lower left-hand side of the diagram maps colors to functional domains in the form of [color]/[PfamA accession]/[functional domain description]/[number of mononegaviruses showing given function].

Mentions: DASH detects homologs between 39/41 mononegaviruses and human (Figure 3 and Table 4). The percent of viral genome shared with the host in the thirty-nine mononegaviruses ranged from 8% (Pneumonia virus of mice) to 75% (Hendra virus), with a median of 44%. Based on the results of Table 4, the median non-retro-transcribing RNA virus shows higher fractions of homologous host genes than the median DNA virus (11%) or median retrovirus (41%) from Table 3.


Domain analysis of symbionts and hosts (DASH) in a genome-wide survey of pathogenic human viruses.

Gonzalez MW, Spouge JL - BMC Res Notes (2013)

Functional domains shared by humans and forty-one RNA non-retro-transcribing viruses. A species tree of the order Mononegavirales from the NCBI taxonomy. Colored dots on the tree show the mononegaviruses with homologous domains in human. The lower left-hand side of the diagram maps colors to functional domains in the form of [color]/[PfamA accession]/[functional domain description]/[number of mononegaviruses showing given function].
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3672079&req=5

Figure 3: Functional domains shared by humans and forty-one RNA non-retro-transcribing viruses. A species tree of the order Mononegavirales from the NCBI taxonomy. Colored dots on the tree show the mononegaviruses with homologous domains in human. The lower left-hand side of the diagram maps colors to functional domains in the form of [color]/[PfamA accession]/[functional domain description]/[number of mononegaviruses showing given function].
Mentions: DASH detects homologs between 39/41 mononegaviruses and human (Figure 3 and Table 4). The percent of viral genome shared with the host in the thirty-nine mononegaviruses ranged from 8% (Pneumonia virus of mice) to 75% (Hendra virus), with a median of 44%. Based on the results of Table 4, the median non-retro-transcribing RNA virus shows higher fractions of homologous host genes than the median DNA virus (11%) or median retrovirus (41%) from Table 3.

Bottom Line: Yet, pairwise-sequence searches have limited sensitivity resulting in poor identification of divergent homologies.Our results indicate that HHV-8 shares at least 29% of its genes with humans (fourteen immunomodulatory and ten metabolic genes).Our results validate our approach, showing that DASH has potential as a pipeline for making therapeutic discoveries in other host-symbiont systems.

View Article: PubMed Central - HTML - PubMed

Affiliation: National Institutes of Health, National Library of Medicine, National Center for Biotechnology Information, 8600 Rockville Pike, Building 38A, Room 6N611-M, Bethesda, MD 20894, USA. mileidywgonzalez@gmail.com

ABSTRACT

Background: In the coevolution of viruses and their hosts, viruses often capture host genes, gaining advantageous functions (e.g. immune system control). Identifying functional similarities shared by viruses and their hosts can help decipher mechanisms of pathogenesis and accelerate virus-targeted drug and vaccine development. Cellular homologs in viruses are usually documented using pairwise-sequence comparison methods. Yet, pairwise-sequence searches have limited sensitivity resulting in poor identification of divergent homologies.

Results: Methods based on profiles from multiple sequences provide a more sensitive alternative to identify similarities in host-pathogen systems. The present work describes a profile-based bioinformatics pipeline that we call the Domain Analysis of Symbionts and Hosts (DASH). DASH provides a web platform for the functional analysis of viral and host genomes. This study uses Human Herpesvirus 8 (HHV-8) as a model to validate the methodology. Our results indicate that HHV-8 shares at least 29% of its genes with humans (fourteen immunomodulatory and ten metabolic genes). DASH also suggests functions for fifty-one additional HHV-8 structural and metabolic proteins. We also perform two other comparative genomics studies of human viruses: (1) a broad survey of eleven viruses of disparate sizes and transcription strategies; and (2) a closer examination of forty-one viruses of the order Mononegavirales. In the survey, DASH detects human homologs in 4/5 DNA viruses. None of the non-retro-transcribing RNA viruses in the survey showed evidence of homology to humans. The order Mononegavirales are also non-retro-transcribing RNA viruses, however, and DASH found homology in 39/41 of them. Mononegaviruses display larger fractions of human similarities (up to 75%) than any of the other RNA or DNA viruses (up to 55% and 29% respectively).

Conclusions: We conclude that gene sharing probably occurs between humans and both DNA and RNA viruses, in viral genomes of differing sizes, regardless of transcription strategies. Our method (DASH) simultaneously analyzes the genomes of two interacting species thereby mining functional information to identify shared as well as exclusive domains to each organism. Our results validate our approach, showing that DASH has potential as a pipeline for making therapeutic discoveries in other host-symbiont systems. DASH results are available at http://tinyurl.com/spouge-dash.

Show MeSH
Related in: MedlinePlus