Massively parallel sequencing and analysis of the Necator americanus transcriptome.

<h4>Background</h4>The blood-feeding hookworm Necator americanus infects hundreds of millions of people worldwide. In order to elucidate fundamental molecular biological aspects of this hookworm, the transcriptome of the adult stage of Necator americanus was explored using next-generatio...

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Autores principales: Cinzia Cantacessi, Makedonka Mitreva, Aaron R Jex, Neil D Young, Bronwyn E Campbell, Ross S Hall, Maria A Doyle, Stuart A Ralph, Elida M Rabelo, Shoba Ranganathan, Paul W Sternberg, Alex Loukas, Robin B Gasser
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spelling oai:doaj.org-article:053f295660fe4b018dcf66c980fd7c822021-12-02T20:24:30ZMassively parallel sequencing and analysis of the Necator americanus transcriptome.1935-27271935-273510.1371/journal.pntd.0000684https://doaj.org/article/053f295660fe4b018dcf66c980fd7c822010-05-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20485481/?tool=EBIhttps://doaj.org/toc/1935-2727https://doaj.org/toc/1935-2735<h4>Background</h4>The blood-feeding hookworm Necator americanus infects hundreds of millions of people worldwide. In order to elucidate fundamental molecular biological aspects of this hookworm, the transcriptome of the adult stage of Necator americanus was explored using next-generation sequencing and bioinformatic analyses.<h4>Methodology/principal findings</h4>A total of 19,997 contigs were assembled from the sequence data; 6,771 of these contigs had known orthologues in the free-living nematode Caenorhabditis elegans, and most of them encoded proteins with WD40 repeats (10.6%), proteinase inhibitors (7.8%) or calcium-binding EF-hand proteins (6.7%). Bioinformatic analyses inferred that the C. elegans homologues are involved mainly in biological pathways linked to ribosome biogenesis (70%), oxidative phosphorylation (63%) and/or proteases (60%); most of these molecules were predicted to be involved in more than one biological pathway. Comparative analyses of the transcriptomes of N. americanus and the canine hookworm, Ancylostoma caninum, revealed qualitative and quantitative differences. For instance, proteinase inhibitors were inferred to be highly represented in the former species, whereas SCP/Tpx-1/Ag5/PR-1/Sc7 proteins ( = SCP/TAPS or Ancylostoma-secreted proteins) were predominant in the latter. In N. americanus, essential molecules were predicted using a combination of orthology mapping and functional data available for C. elegans. Further analyses allowed the prioritization of 18 predicted drug targets which did not have homologues in the human host. These candidate targets were inferred to be linked to mitochondrial (e.g., processing proteins) or amino acid metabolism (e.g., asparagine t-RNA synthetase).<h4>Conclusions</h4>This study has provided detailed insights into the transcriptome of the adult stage of N. americanus and examines similarities and differences between this species and A. caninum. Future efforts should focus on comparative transcriptomic and proteomic investigations of the other predominant human hookworm, A. duodenale, for both fundamental and applied purposes, including the prevalidation of anti-hookworm drug targets.Cinzia CantacessiMakedonka MitrevaAaron R JexNeil D YoungBronwyn E CampbellRoss S HallMaria A DoyleStuart A RalphElida M RabeloShoba RanganathanPaul W SternbergAlex LoukasRobin B GasserPublic Library of Science (PLoS)articleArctic medicine. Tropical medicineRC955-962Public aspects of medicineRA1-1270ENPLoS Neglected Tropical Diseases, Vol 4, Iss 5, p e684 (2010)
institution DOAJ
collection DOAJ
language EN
topic Arctic medicine. Tropical medicine
RC955-962
Public aspects of medicine
RA1-1270
spellingShingle Arctic medicine. Tropical medicine
RC955-962
Public aspects of medicine
RA1-1270
Cinzia Cantacessi
Makedonka Mitreva
Aaron R Jex
Neil D Young
Bronwyn E Campbell
Ross S Hall
Maria A Doyle
Stuart A Ralph
Elida M Rabelo
Shoba Ranganathan
Paul W Sternberg
Alex Loukas
Robin B Gasser
Massively parallel sequencing and analysis of the Necator americanus transcriptome.
description <h4>Background</h4>The blood-feeding hookworm Necator americanus infects hundreds of millions of people worldwide. In order to elucidate fundamental molecular biological aspects of this hookworm, the transcriptome of the adult stage of Necator americanus was explored using next-generation sequencing and bioinformatic analyses.<h4>Methodology/principal findings</h4>A total of 19,997 contigs were assembled from the sequence data; 6,771 of these contigs had known orthologues in the free-living nematode Caenorhabditis elegans, and most of them encoded proteins with WD40 repeats (10.6%), proteinase inhibitors (7.8%) or calcium-binding EF-hand proteins (6.7%). Bioinformatic analyses inferred that the C. elegans homologues are involved mainly in biological pathways linked to ribosome biogenesis (70%), oxidative phosphorylation (63%) and/or proteases (60%); most of these molecules were predicted to be involved in more than one biological pathway. Comparative analyses of the transcriptomes of N. americanus and the canine hookworm, Ancylostoma caninum, revealed qualitative and quantitative differences. For instance, proteinase inhibitors were inferred to be highly represented in the former species, whereas SCP/Tpx-1/Ag5/PR-1/Sc7 proteins ( = SCP/TAPS or Ancylostoma-secreted proteins) were predominant in the latter. In N. americanus, essential molecules were predicted using a combination of orthology mapping and functional data available for C. elegans. Further analyses allowed the prioritization of 18 predicted drug targets which did not have homologues in the human host. These candidate targets were inferred to be linked to mitochondrial (e.g., processing proteins) or amino acid metabolism (e.g., asparagine t-RNA synthetase).<h4>Conclusions</h4>This study has provided detailed insights into the transcriptome of the adult stage of N. americanus and examines similarities and differences between this species and A. caninum. Future efforts should focus on comparative transcriptomic and proteomic investigations of the other predominant human hookworm, A. duodenale, for both fundamental and applied purposes, including the prevalidation of anti-hookworm drug targets.
format article
author Cinzia Cantacessi
Makedonka Mitreva
Aaron R Jex
Neil D Young
Bronwyn E Campbell
Ross S Hall
Maria A Doyle
Stuart A Ralph
Elida M Rabelo
Shoba Ranganathan
Paul W Sternberg
Alex Loukas
Robin B Gasser
author_facet Cinzia Cantacessi
Makedonka Mitreva
Aaron R Jex
Neil D Young
Bronwyn E Campbell
Ross S Hall
Maria A Doyle
Stuart A Ralph
Elida M Rabelo
Shoba Ranganathan
Paul W Sternberg
Alex Loukas
Robin B Gasser
author_sort Cinzia Cantacessi
title Massively parallel sequencing and analysis of the Necator americanus transcriptome.
title_short Massively parallel sequencing and analysis of the Necator americanus transcriptome.
title_full Massively parallel sequencing and analysis of the Necator americanus transcriptome.
title_fullStr Massively parallel sequencing and analysis of the Necator americanus transcriptome.
title_full_unstemmed Massively parallel sequencing and analysis of the Necator americanus transcriptome.
title_sort massively parallel sequencing and analysis of the necator americanus transcriptome.
publisher Public Library of Science (PLoS)
publishDate 2010
url https://doaj.org/article/053f295660fe4b018dcf66c980fd7c82
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