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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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) |
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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. |
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<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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