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Needles in the EST haystack: large-scale identification and analysis of excretory-secretory (ES) proteins in parasitic nematodes using expressed sequence tags (ESTs).

Nagaraj SH, Gasser RB, Ranganathan S - PLoS Negl Trop Dis (2008)

Bottom Line: Of these 4,710 proteins, 2,490 (52.8%) had orthologues in Caenorhabditis elegans, whereas 621 (13.8%) appeared to be novel, currently having no significant match to any molecule available in public databases.We report the large-scale analysis of ES proteins inferred from EST data for a range of parasitic nematodes.This set of ES proteins provides an inventory of known and novel members of ES proteins as a foundation for studies focused on understanding the biology of parasitic nematodes and their interactions with their hosts, as well as for the development of novel drugs or vaccines for parasite intervention and control.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry and Biomolecular Sciences, Macquarie University, Sydney, New South Wales, Australia.

ABSTRACT

Background: Parasitic nematodes of humans, other animals and plants continue to impose a significant public health and economic burden worldwide, due to the diseases they cause. Promising antiparasitic drug and vaccine candidates have been discovered from excreted or secreted (ES) proteins released from the parasite and exposed to the immune system of the host. Mining the entire expressed sequence tag (EST) data available from parasitic nematodes represents an approach to discover such ES targets.

Methods and findings: In this study, we predicted, using EST2Secretome, a novel, high-throughput, computational workflow system, 4,710 ES proteins from 452,134 ESTs derived from 39 different species of nematodes, parasitic in animals (including humans) or plants. In total, 2,632, 786, and 1,292 ES proteins were predicted for animal-, human-, and plant-parasitic nematodes. Subsequently, we systematically analysed ES proteins using computational methods. Of these 4,710 proteins, 2,490 (52.8%) had orthologues in Caenorhabditis elegans, whereas 621 (13.8%) appeared to be novel, currently having no significant match to any molecule available in public databases. Of the C. elegans homologues, 267 had strong "loss-of-function" phenotypes by RNA interference (RNAi) in this nematode. We could functionally classify 1,948 (41.3%) sequences using the Gene Ontology (GO) terms, establish pathway associations for 573 (12.2%) sequences using Kyoto Encyclopaedia of Genes and Genomes (KEGG), and identify protein interaction partners for 1,774 (37.6%) molecules. We also mapped 758 (16.1%) proteins to protein domains including the nematode-specific protein family "transthyretin-like" and "chromadorea ALT," considered as vaccine candidates against filariasis in humans.

Conclusions: We report the large-scale analysis of ES proteins inferred from EST data for a range of parasitic nematodes. This set of ES proteins provides an inventory of known and novel members of ES proteins as a foundation for studies focused on understanding the biology of parasitic nematodes and their interactions with their hosts, as well as for the development of novel drugs or vaccines for parasite intervention and control.

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Schematic representation of EST2Secretome workflow.EST2Secretome analysis comprising Phase I: pre-processing, assembly and conceptual translation, Phase II: identification of putative excretory-secretory (ES) proteins and Phase III: annotation of ES proteins using a suite of computational tools.
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pntd-0000301-g001: Schematic representation of EST2Secretome workflow.EST2Secretome analysis comprising Phase I: pre-processing, assembly and conceptual translation, Phase II: identification of putative excretory-secretory (ES) proteins and Phase III: annotation of ES proteins using a suite of computational tools.

Mentions: Phase I of EST2Secretome shares SeqClean, RepeatMasker and CAP3 (contig assembly program) programs with ESTExplorer [26], based on the analysis presented elsewhere [20]. The contig and singleton sequences generated by CAP3 are transferred to the program ESTScan [27] for conceptual translation into proteins, using the genetic code from the nearest organism. EST2Secretome currently implements the genetic codes for 15 organisms, covering the most studied organisms, including human, mouse, rat, pig, dog, chicken, rice, wheat, thale cress (Arabidopsis thaliana), zebrafish, fly, yeast and a free-living roundworm (Caenorhabditis elegans) (Figure 1).


Needles in the EST haystack: large-scale identification and analysis of excretory-secretory (ES) proteins in parasitic nematodes using expressed sequence tags (ESTs).

Nagaraj SH, Gasser RB, Ranganathan S - PLoS Negl Trop Dis (2008)

Schematic representation of EST2Secretome workflow.EST2Secretome analysis comprising Phase I: pre-processing, assembly and conceptual translation, Phase II: identification of putative excretory-secretory (ES) proteins and Phase III: annotation of ES proteins using a suite of computational tools.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2553489&req=5

pntd-0000301-g001: Schematic representation of EST2Secretome workflow.EST2Secretome analysis comprising Phase I: pre-processing, assembly and conceptual translation, Phase II: identification of putative excretory-secretory (ES) proteins and Phase III: annotation of ES proteins using a suite of computational tools.
Mentions: Phase I of EST2Secretome shares SeqClean, RepeatMasker and CAP3 (contig assembly program) programs with ESTExplorer [26], based on the analysis presented elsewhere [20]. The contig and singleton sequences generated by CAP3 are transferred to the program ESTScan [27] for conceptual translation into proteins, using the genetic code from the nearest organism. EST2Secretome currently implements the genetic codes for 15 organisms, covering the most studied organisms, including human, mouse, rat, pig, dog, chicken, rice, wheat, thale cress (Arabidopsis thaliana), zebrafish, fly, yeast and a free-living roundworm (Caenorhabditis elegans) (Figure 1).

Bottom Line: Of these 4,710 proteins, 2,490 (52.8%) had orthologues in Caenorhabditis elegans, whereas 621 (13.8%) appeared to be novel, currently having no significant match to any molecule available in public databases.We report the large-scale analysis of ES proteins inferred from EST data for a range of parasitic nematodes.This set of ES proteins provides an inventory of known and novel members of ES proteins as a foundation for studies focused on understanding the biology of parasitic nematodes and their interactions with their hosts, as well as for the development of novel drugs or vaccines for parasite intervention and control.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry and Biomolecular Sciences, Macquarie University, Sydney, New South Wales, Australia.

ABSTRACT

Background: Parasitic nematodes of humans, other animals and plants continue to impose a significant public health and economic burden worldwide, due to the diseases they cause. Promising antiparasitic drug and vaccine candidates have been discovered from excreted or secreted (ES) proteins released from the parasite and exposed to the immune system of the host. Mining the entire expressed sequence tag (EST) data available from parasitic nematodes represents an approach to discover such ES targets.

Methods and findings: In this study, we predicted, using EST2Secretome, a novel, high-throughput, computational workflow system, 4,710 ES proteins from 452,134 ESTs derived from 39 different species of nematodes, parasitic in animals (including humans) or plants. In total, 2,632, 786, and 1,292 ES proteins were predicted for animal-, human-, and plant-parasitic nematodes. Subsequently, we systematically analysed ES proteins using computational methods. Of these 4,710 proteins, 2,490 (52.8%) had orthologues in Caenorhabditis elegans, whereas 621 (13.8%) appeared to be novel, currently having no significant match to any molecule available in public databases. Of the C. elegans homologues, 267 had strong "loss-of-function" phenotypes by RNA interference (RNAi) in this nematode. We could functionally classify 1,948 (41.3%) sequences using the Gene Ontology (GO) terms, establish pathway associations for 573 (12.2%) sequences using Kyoto Encyclopaedia of Genes and Genomes (KEGG), and identify protein interaction partners for 1,774 (37.6%) molecules. We also mapped 758 (16.1%) proteins to protein domains including the nematode-specific protein family "transthyretin-like" and "chromadorea ALT," considered as vaccine candidates against filariasis in humans.

Conclusions: We report the large-scale analysis of ES proteins inferred from EST data for a range of parasitic nematodes. This set of ES proteins provides an inventory of known and novel members of ES proteins as a foundation for studies focused on understanding the biology of parasitic nematodes and their interactions with their hosts, as well as for the development of novel drugs or vaccines for parasite intervention and control.

Show MeSH
Related in: MedlinePlus