Computational analysis and experimental validation of gene predictions in Toxoplasma gondii.

<h4>Background</h4>Toxoplasma gondii is an obligate intracellular protozoan that infects 20 to 90% of the population. It can cause both acute and chronic infections, many of which are asymptomatic, and, in immunocompromised hosts, can cause fatal infection due to reactivation from an asy...

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Main Authors: Joseph M Dybas, Carlos J Madrid-Aliste, Fa-Yun Che, Edward Nieves, Dmitry Rykunov, Ruth Hogue Angeletti, Louis M Weiss, Kami Kim, Andras Fiser
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2008-01-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0003899&type=printable
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author Joseph M Dybas
Carlos J Madrid-Aliste
Fa-Yun Che
Edward Nieves
Dmitry Rykunov
Ruth Hogue Angeletti
Louis M Weiss
Kami Kim
Andras Fiser
author_facet Joseph M Dybas
Carlos J Madrid-Aliste
Fa-Yun Che
Edward Nieves
Dmitry Rykunov
Ruth Hogue Angeletti
Louis M Weiss
Kami Kim
Andras Fiser
author_sort Joseph M Dybas
collection DOAJ
description <h4>Background</h4>Toxoplasma gondii is an obligate intracellular protozoan that infects 20 to 90% of the population. It can cause both acute and chronic infections, many of which are asymptomatic, and, in immunocompromised hosts, can cause fatal infection due to reactivation from an asymptomatic chronic infection. An essential step towards understanding molecular mechanisms controlling transitions between the various life stages and identifying candidate drug targets is to accurately characterize the T. gondii proteome.<h4>Methodology/principal findings</h4>We have explored the proteome of T. gondii tachyzoites with high throughput proteomics experiments and by comparison to publicly available cDNA sequence data. Mass spectrometry analysis validated 2,477 gene coding regions with 6,438 possible alternative gene predictions; approximately one third of the T. gondii proteome. The proteomics survey identified 609 proteins that are unique to Toxoplasma as compared to any known species including other Apicomplexan. Computational analysis identified 787 cases of possible gene duplication events and located at least 6,089 gene coding regions. Commonly used gene prediction algorithms produce very disparate sets of protein sequences, with pairwise overlaps ranging from 1.4% to 12%. Through this experimental and computational exercise we benchmarked gene prediction methods and observed false negative rates of 31 to 43%.<h4>Conclusions/significance</h4>This study not only provides the largest proteomics exploration of the T. gondii proteome, but illustrates how high throughput proteomics experiments can elucidate correct gene structures in genomes.
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spelling doaj-art-c6d74269926f478db88cc441996b1e102025-08-20T02:38:29ZengPublic Library of Science (PLoS)PLoS ONE1932-62032008-01-01312e389910.1371/journal.pone.0003899Computational analysis and experimental validation of gene predictions in Toxoplasma gondii.Joseph M DybasCarlos J Madrid-AlisteFa-Yun CheEdward NievesDmitry RykunovRuth Hogue AngelettiLouis M WeissKami KimAndras Fiser<h4>Background</h4>Toxoplasma gondii is an obligate intracellular protozoan that infects 20 to 90% of the population. It can cause both acute and chronic infections, many of which are asymptomatic, and, in immunocompromised hosts, can cause fatal infection due to reactivation from an asymptomatic chronic infection. An essential step towards understanding molecular mechanisms controlling transitions between the various life stages and identifying candidate drug targets is to accurately characterize the T. gondii proteome.<h4>Methodology/principal findings</h4>We have explored the proteome of T. gondii tachyzoites with high throughput proteomics experiments and by comparison to publicly available cDNA sequence data. Mass spectrometry analysis validated 2,477 gene coding regions with 6,438 possible alternative gene predictions; approximately one third of the T. gondii proteome. The proteomics survey identified 609 proteins that are unique to Toxoplasma as compared to any known species including other Apicomplexan. Computational analysis identified 787 cases of possible gene duplication events and located at least 6,089 gene coding regions. Commonly used gene prediction algorithms produce very disparate sets of protein sequences, with pairwise overlaps ranging from 1.4% to 12%. Through this experimental and computational exercise we benchmarked gene prediction methods and observed false negative rates of 31 to 43%.<h4>Conclusions/significance</h4>This study not only provides the largest proteomics exploration of the T. gondii proteome, but illustrates how high throughput proteomics experiments can elucidate correct gene structures in genomes.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0003899&type=printable
spellingShingle Joseph M Dybas
Carlos J Madrid-Aliste
Fa-Yun Che
Edward Nieves
Dmitry Rykunov
Ruth Hogue Angeletti
Louis M Weiss
Kami Kim
Andras Fiser
Computational analysis and experimental validation of gene predictions in Toxoplasma gondii.
PLoS ONE
title Computational analysis and experimental validation of gene predictions in Toxoplasma gondii.
title_full Computational analysis and experimental validation of gene predictions in Toxoplasma gondii.
title_fullStr Computational analysis and experimental validation of gene predictions in Toxoplasma gondii.
title_full_unstemmed Computational analysis and experimental validation of gene predictions in Toxoplasma gondii.
title_short Computational analysis and experimental validation of gene predictions in Toxoplasma gondii.
title_sort computational analysis and experimental validation of gene predictions in toxoplasma gondii
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0003899&type=printable
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