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Deciphering RNA Regulatory Elements Involved in the Developmental and Environmental Gene Regulation of Trypanosoma brucei.

Gazestani VH, Salavati R - PLoS ONE (2015)

Bottom Line: Here, benefiting from a new graph-based approach for finding functional regulatory elements in RNA (GRAFFER), we have predicted 88 new RNA regulatory elements that are potentially involved in the gene regulatory network of T. brucei.Moreover, we found that 11 of predicted elements strikingly resemble previously identified regulatory elements for the parasite.Additionally, comparison with previously predicted motifs on T. brucei suggested the superior performance of our approach based on the current limited knowledge of regulatory elements in T. brucei.

View Article: PubMed Central - PubMed

Affiliation: Institute of Parasitology, McGill University, 21111 Lakeshore Road, Ste. Anne de Bellevue, Montreal, Quebec, Canada.

ABSTRACT
Trypanosoma brucei is a vector-borne parasite with intricate life cycle that can cause serious diseases in humans and animals. This pathogen relies on fine regulation of gene expression to respond and adapt to variable environments, with implications in transmission and infectivity. However, the involved regulatory elements and their mechanisms of actions are largely unknown. Here, benefiting from a new graph-based approach for finding functional regulatory elements in RNA (GRAFFER), we have predicted 88 new RNA regulatory elements that are potentially involved in the gene regulatory network of T. brucei. We show that many of these newly predicted elements are responsive to both transcriptomic and proteomic changes during the life cycle of the parasite. Moreover, we found that 11 of predicted elements strikingly resemble previously identified regulatory elements for the parasite. Additionally, comparison with previously predicted motifs on T. brucei suggested the superior performance of our approach based on the current limited knowledge of regulatory elements in T. brucei.

No MeSH data available.


Related in: MedlinePlus

Motif enrichment analysis using available transcriptome and proteome data of T. brucei.For each GRAFFER motif, transcripts containing the motif in their 3′-UTR were selected and then tested for a statistically significant pattern in each cell state using standard Mann-Whitney rank sum statistic. (a) Developmental transcriptome responses of the eleven GRAFFER motifs that matched with the previously known RREs in T. brucei. For illustrative purposes, the full transcriptome enrichment analysis for the rest of the predicted motifs is not represented here. The complete results of this analysis are illustrated in S8 and S9 Figs. (b) Proteome enrichment analysis revealed that 19 motifs showed significant enrichment under at least one condition. The outer layer of circle indicates the motif id, excluding “GBM_TB” term due to illustration limitations. The intermediate circular layers indicate the up- or down-regulation of the motifs in a specific condition. The inner circular layer represents the consensus patterns of motifs. The center of circle shows the conditions that were tested for the enrichment with the reference for the study that data was extracted from.
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pone.0142342.g002: Motif enrichment analysis using available transcriptome and proteome data of T. brucei.For each GRAFFER motif, transcripts containing the motif in their 3′-UTR were selected and then tested for a statistically significant pattern in each cell state using standard Mann-Whitney rank sum statistic. (a) Developmental transcriptome responses of the eleven GRAFFER motifs that matched with the previously known RREs in T. brucei. For illustrative purposes, the full transcriptome enrichment analysis for the rest of the predicted motifs is not represented here. The complete results of this analysis are illustrated in S8 and S9 Figs. (b) Proteome enrichment analysis revealed that 19 motifs showed significant enrichment under at least one condition. The outer layer of circle indicates the motif id, excluding “GBM_TB” term due to illustration limitations. The intermediate circular layers indicate the up- or down-regulation of the motifs in a specific condition. The inner circular layer represents the consensus patterns of motifs. The center of circle shows the conditions that were tested for the enrichment with the reference for the study that data was extracted from.

Mentions: Additionally, we examined whether the predicted motifs showed specific expression patterns in the transcriptome data of each cell state. This analysis revealed that 84 out of 88 (95%) predicted motifs showed significant enrichment under at least one condition (Fig 2a and S8 and S9 Figs in S1 Text). We also considered the available proteomics data [32–34] to further demonstrate the functionality of predicted motifs at the proteome level. Following the same approach as the transcriptome data, we found that 19 motifs (22%) showed significant enrichment under at least one condition (Fig 2b). Notably, the available proteomics data, compared with the transcriptome data, were from a limited set of conditions. Therefore, we can expect this number to increase as more proteomic data becomes available. As discussed later, we show that enrichment results for several motifs are consistent with previous knowledge on the gene regulatory network of T. brucei.


Deciphering RNA Regulatory Elements Involved in the Developmental and Environmental Gene Regulation of Trypanosoma brucei.

Gazestani VH, Salavati R - PLoS ONE (2015)

Motif enrichment analysis using available transcriptome and proteome data of T. brucei.For each GRAFFER motif, transcripts containing the motif in their 3′-UTR were selected and then tested for a statistically significant pattern in each cell state using standard Mann-Whitney rank sum statistic. (a) Developmental transcriptome responses of the eleven GRAFFER motifs that matched with the previously known RREs in T. brucei. For illustrative purposes, the full transcriptome enrichment analysis for the rest of the predicted motifs is not represented here. The complete results of this analysis are illustrated in S8 and S9 Figs. (b) Proteome enrichment analysis revealed that 19 motifs showed significant enrichment under at least one condition. The outer layer of circle indicates the motif id, excluding “GBM_TB” term due to illustration limitations. The intermediate circular layers indicate the up- or down-regulation of the motifs in a specific condition. The inner circular layer represents the consensus patterns of motifs. The center of circle shows the conditions that were tested for the enrichment with the reference for the study that data was extracted from.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4631447&req=5

pone.0142342.g002: Motif enrichment analysis using available transcriptome and proteome data of T. brucei.For each GRAFFER motif, transcripts containing the motif in their 3′-UTR were selected and then tested for a statistically significant pattern in each cell state using standard Mann-Whitney rank sum statistic. (a) Developmental transcriptome responses of the eleven GRAFFER motifs that matched with the previously known RREs in T. brucei. For illustrative purposes, the full transcriptome enrichment analysis for the rest of the predicted motifs is not represented here. The complete results of this analysis are illustrated in S8 and S9 Figs. (b) Proteome enrichment analysis revealed that 19 motifs showed significant enrichment under at least one condition. The outer layer of circle indicates the motif id, excluding “GBM_TB” term due to illustration limitations. The intermediate circular layers indicate the up- or down-regulation of the motifs in a specific condition. The inner circular layer represents the consensus patterns of motifs. The center of circle shows the conditions that were tested for the enrichment with the reference for the study that data was extracted from.
Mentions: Additionally, we examined whether the predicted motifs showed specific expression patterns in the transcriptome data of each cell state. This analysis revealed that 84 out of 88 (95%) predicted motifs showed significant enrichment under at least one condition (Fig 2a and S8 and S9 Figs in S1 Text). We also considered the available proteomics data [32–34] to further demonstrate the functionality of predicted motifs at the proteome level. Following the same approach as the transcriptome data, we found that 19 motifs (22%) showed significant enrichment under at least one condition (Fig 2b). Notably, the available proteomics data, compared with the transcriptome data, were from a limited set of conditions. Therefore, we can expect this number to increase as more proteomic data becomes available. As discussed later, we show that enrichment results for several motifs are consistent with previous knowledge on the gene regulatory network of T. brucei.

Bottom Line: Here, benefiting from a new graph-based approach for finding functional regulatory elements in RNA (GRAFFER), we have predicted 88 new RNA regulatory elements that are potentially involved in the gene regulatory network of T. brucei.Moreover, we found that 11 of predicted elements strikingly resemble previously identified regulatory elements for the parasite.Additionally, comparison with previously predicted motifs on T. brucei suggested the superior performance of our approach based on the current limited knowledge of regulatory elements in T. brucei.

View Article: PubMed Central - PubMed

Affiliation: Institute of Parasitology, McGill University, 21111 Lakeshore Road, Ste. Anne de Bellevue, Montreal, Quebec, Canada.

ABSTRACT
Trypanosoma brucei is a vector-borne parasite with intricate life cycle that can cause serious diseases in humans and animals. This pathogen relies on fine regulation of gene expression to respond and adapt to variable environments, with implications in transmission and infectivity. However, the involved regulatory elements and their mechanisms of actions are largely unknown. Here, benefiting from a new graph-based approach for finding functional regulatory elements in RNA (GRAFFER), we have predicted 88 new RNA regulatory elements that are potentially involved in the gene regulatory network of T. brucei. We show that many of these newly predicted elements are responsive to both transcriptomic and proteomic changes during the life cycle of the parasite. Moreover, we found that 11 of predicted elements strikingly resemble previously identified regulatory elements for the parasite. Additionally, comparison with previously predicted motifs on T. brucei suggested the superior performance of our approach based on the current limited knowledge of regulatory elements in T. brucei.

No MeSH data available.


Related in: MedlinePlus