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Development of the first oligonucleotide microarray for global gene expression profiling in guinea pigs: defining the transcription signature of infectious diseases.

Jain R, Dey B, Tyagi AK - BMC Genomics (2012)

Bottom Line: To validate and demonstrate the merit of this microarray, we have studied, as an example, the expression profile of guinea pig lungs during the advanced phase of M. tuberculosis infection.A significant upregulation of 1344 genes and a marked down regulation of 1856 genes in the lungs identified a disease signature of pulmonary tuberculosis infection.An important gap in the area of infectious diseases has been addressed and a valuable molecular tool is provided to optimally harness the potential of guinea pig model to develop better vaccines and therapies against human diseases.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biochemistry, University of Delhi South Campus, Benito Juarez Road, New Delhi, 110021, India.

ABSTRACT

Background: The Guinea pig (Cavia porcellus) is one of the most extensively used animal models to study infectious diseases. However, despite its tremendous contribution towards understanding the establishment, progression and control of a number of diseases in general and tuberculosis in particular, the lack of fully annotated guinea pig genome sequence as well as appropriate molecular reagents has severely hampered detailed genetic and immunological analysis in this animal model.

Results: By employing the cross-species hybridization technique, we have developed an oligonucleotide microarray with 44,000 features assembled from different mammalian species, which to the best of our knowledge is the first attempt to employ microarray to study the global gene expression profile in guinea pigs. To validate and demonstrate the merit of this microarray, we have studied, as an example, the expression profile of guinea pig lungs during the advanced phase of M. tuberculosis infection. A significant upregulation of 1344 genes and a marked down regulation of 1856 genes in the lungs identified a disease signature of pulmonary tuberculosis infection.

Conclusion: We report the development of first comprehensive microarray for studying the global gene expression profile in guinea pigs and validation of its usefulness with tuberculosis as a case study. An important gap in the area of infectious diseases has been addressed and a valuable molecular tool is provided to optimally harness the potential of guinea pig model to develop better vaccines and therapies against human diseases.

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Pulmonary gene expression signature of guinea pigs at 10 weeks post M. tuberculosis infection. Transcriptional profile of lungs of guinea pig was analysed by microarray. The figure depicts the clustered heat maps obtained thereof for the genes expressed in a differential manner between the experimental and control groups. By using unsupervised hierarchical clustering algorithm, the most similar expression profiles are joined together to form a group. These are further joined in a tree structure, until all data forms a single group. Clustering is based on Average- distance between two clusters, which is the average of the pair-wise distance between entities in the two clusters. For the measurement of similarity between conditions, Pearson coefficient correlation clustering algorithm is used. The color scheme for the hierarchical clustering is yellow: no change in expression, magenta: higher expression in infected lungs relative to normal lungs and green: lower expression in infected samples relative to normal uninfected lungs. 1: Uninfected lung; 2: Infected Lung 1; 3: Infected Lung 2; 4: Infected Lung 3.
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Figure 3: Pulmonary gene expression signature of guinea pigs at 10 weeks post M. tuberculosis infection. Transcriptional profile of lungs of guinea pig was analysed by microarray. The figure depicts the clustered heat maps obtained thereof for the genes expressed in a differential manner between the experimental and control groups. By using unsupervised hierarchical clustering algorithm, the most similar expression profiles are joined together to form a group. These are further joined in a tree structure, until all data forms a single group. Clustering is based on Average- distance between two clusters, which is the average of the pair-wise distance between entities in the two clusters. For the measurement of similarity between conditions, Pearson coefficient correlation clustering algorithm is used. The color scheme for the hierarchical clustering is yellow: no change in expression, magenta: higher expression in infected lungs relative to normal lungs and green: lower expression in infected samples relative to normal uninfected lungs. 1: Uninfected lung; 2: Infected Lung 1; 3: Infected Lung 2; 4: Infected Lung 3.

Mentions: Based on this, several unique genes were identified that exhibited a significant regulation in response to infection. While, 1344 unique genes exhibited a marked up regulation, 1856 genes were significantly down regulated in the lungs of infected guinea pigs as compared to the lungs of uninfected animals as depicted by a heat map in Figure3. The genes exhibiting significant regulation are listed in Additional file3.


Development of the first oligonucleotide microarray for global gene expression profiling in guinea pigs: defining the transcription signature of infectious diseases.

Jain R, Dey B, Tyagi AK - BMC Genomics (2012)

Pulmonary gene expression signature of guinea pigs at 10 weeks post M. tuberculosis infection. Transcriptional profile of lungs of guinea pig was analysed by microarray. The figure depicts the clustered heat maps obtained thereof for the genes expressed in a differential manner between the experimental and control groups. By using unsupervised hierarchical clustering algorithm, the most similar expression profiles are joined together to form a group. These are further joined in a tree structure, until all data forms a single group. Clustering is based on Average- distance between two clusters, which is the average of the pair-wise distance between entities in the two clusters. For the measurement of similarity between conditions, Pearson coefficient correlation clustering algorithm is used. The color scheme for the hierarchical clustering is yellow: no change in expression, magenta: higher expression in infected lungs relative to normal lungs and green: lower expression in infected samples relative to normal uninfected lungs. 1: Uninfected lung; 2: Infected Lung 1; 3: Infected Lung 2; 4: Infected Lung 3.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3475082&req=5

Figure 3: Pulmonary gene expression signature of guinea pigs at 10 weeks post M. tuberculosis infection. Transcriptional profile of lungs of guinea pig was analysed by microarray. The figure depicts the clustered heat maps obtained thereof for the genes expressed in a differential manner between the experimental and control groups. By using unsupervised hierarchical clustering algorithm, the most similar expression profiles are joined together to form a group. These are further joined in a tree structure, until all data forms a single group. Clustering is based on Average- distance between two clusters, which is the average of the pair-wise distance between entities in the two clusters. For the measurement of similarity between conditions, Pearson coefficient correlation clustering algorithm is used. The color scheme for the hierarchical clustering is yellow: no change in expression, magenta: higher expression in infected lungs relative to normal lungs and green: lower expression in infected samples relative to normal uninfected lungs. 1: Uninfected lung; 2: Infected Lung 1; 3: Infected Lung 2; 4: Infected Lung 3.
Mentions: Based on this, several unique genes were identified that exhibited a significant regulation in response to infection. While, 1344 unique genes exhibited a marked up regulation, 1856 genes were significantly down regulated in the lungs of infected guinea pigs as compared to the lungs of uninfected animals as depicted by a heat map in Figure3. The genes exhibiting significant regulation are listed in Additional file3.

Bottom Line: To validate and demonstrate the merit of this microarray, we have studied, as an example, the expression profile of guinea pig lungs during the advanced phase of M. tuberculosis infection.A significant upregulation of 1344 genes and a marked down regulation of 1856 genes in the lungs identified a disease signature of pulmonary tuberculosis infection.An important gap in the area of infectious diseases has been addressed and a valuable molecular tool is provided to optimally harness the potential of guinea pig model to develop better vaccines and therapies against human diseases.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biochemistry, University of Delhi South Campus, Benito Juarez Road, New Delhi, 110021, India.

ABSTRACT

Background: The Guinea pig (Cavia porcellus) is one of the most extensively used animal models to study infectious diseases. However, despite its tremendous contribution towards understanding the establishment, progression and control of a number of diseases in general and tuberculosis in particular, the lack of fully annotated guinea pig genome sequence as well as appropriate molecular reagents has severely hampered detailed genetic and immunological analysis in this animal model.

Results: By employing the cross-species hybridization technique, we have developed an oligonucleotide microarray with 44,000 features assembled from different mammalian species, which to the best of our knowledge is the first attempt to employ microarray to study the global gene expression profile in guinea pigs. To validate and demonstrate the merit of this microarray, we have studied, as an example, the expression profile of guinea pig lungs during the advanced phase of M. tuberculosis infection. A significant upregulation of 1344 genes and a marked down regulation of 1856 genes in the lungs identified a disease signature of pulmonary tuberculosis infection.

Conclusion: We report the development of first comprehensive microarray for studying the global gene expression profile in guinea pigs and validation of its usefulness with tuberculosis as a case study. An important gap in the area of infectious diseases has been addressed and a valuable molecular tool is provided to optimally harness the potential of guinea pig model to develop better vaccines and therapies against human diseases.

Show MeSH
Related in: MedlinePlus