Limits...
Gene set enrichment analysis identifies LIF as a negative regulator of human Th2 cell differentiation.

Ullah U, Tripathi P, Lahesmaa R, Rao KV - Sci Rep (2012)

Bottom Line: In this study we show that IL-4 is crucial during reinforcement window of human Th2 differentiation for optimal Th2 development.We have also shown here that during this stage, IL-4 helps in cellular decision-making process of differentiation versus proliferation.This approach can be generalized to analyze "omics" data to identify key regulatory modules.

View Article: PubMed Central - PubMed

Affiliation: Immunology Group International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi-110067, India.

ABSTRACT
In this study we show that IL-4 is crucial during reinforcement window of human Th2 differentiation for optimal Th2 development. We have also shown here that during this stage, IL-4 helps in cellular decision-making process of differentiation versus proliferation. We have combined computational and experimental methods to analyze Th2 transcription network to name novel players of the process of Th2 differentiation. Here we report that LIF through STAT3 negatively regulates Th2 differentiation. This approach can be generalized to analyze "omics" data to identify key regulatory modules.

Show MeSH

Related in: MedlinePlus

Gene Set Enrichment Analysis (GSEA).Panel a shows enrichment score (ES) distribution of all the enriched gene sets. Panel b shows variation of p value (Red) and q value (Blue) with Normalized Enrichment Score (NES). Please see text for detail. Panel c is a network of all core enriched genes of all the pathways taken together. Node size is a measure of Betweenness Centrality (BC). Larger is the size higher is the BC. Nodes with highest BC values are highlighted in yellow. Panel d shows degree distribution of network shown in panel c with fitted power law line.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3376453&req=5

f3: Gene Set Enrichment Analysis (GSEA).Panel a shows enrichment score (ES) distribution of all the enriched gene sets. Panel b shows variation of p value (Red) and q value (Blue) with Normalized Enrichment Score (NES). Please see text for detail. Panel c is a network of all core enriched genes of all the pathways taken together. Node size is a measure of Betweenness Centrality (BC). Larger is the size higher is the BC. Nodes with highest BC values are highlighted in yellow. Panel d shows degree distribution of network shown in panel c with fitted power law line.

Mentions: To identify pathways enriched in TIL4 treated samples over the samples treated with neutralizing antibodies, GSEA was performed on day 6transcription data. Results are shown in Table 5. Overview of GSEA analysis is illustrated in Figure 3a and b. Panel a shows distribution of enrichment score (ES) of all the gene sets enriched. On the X axis, gene sets that are present before “0” mark were overrepresented in the background set and those that are present after it were the sets enriched in the test set (TIL4 as opposed to TIL4ABS group). A dot plot of significance and Normalized Enrichment Score NES for is given in Figure 3b. This Figure (Figure 3b) shows that gene sets bearing NES, either less than -1 or more than +1 are significant at the cut off FDR q value of less than 25 %. Although in TIL4ABS samples, there were many gene sets with nominal p value less than 0.25, or even 0.05, but none of them was enriched at FDR q value of less than 0.25. The nominal p value is less relevant for comparing across the gene sets than FDR q value. Parameters used for the analysis are detailed in Methods section. Details on statistics used are described elsewhere17. As shown in Table 5 many pathways known to be associated with cytokine signaling were enriched in TCR + IL-4 treated sample. Enriched pathways can be classified under the heads of signaling pathways and metabolic pathways.


Gene set enrichment analysis identifies LIF as a negative regulator of human Th2 cell differentiation.

Ullah U, Tripathi P, Lahesmaa R, Rao KV - Sci Rep (2012)

Gene Set Enrichment Analysis (GSEA).Panel a shows enrichment score (ES) distribution of all the enriched gene sets. Panel b shows variation of p value (Red) and q value (Blue) with Normalized Enrichment Score (NES). Please see text for detail. Panel c is a network of all core enriched genes of all the pathways taken together. Node size is a measure of Betweenness Centrality (BC). Larger is the size higher is the BC. Nodes with highest BC values are highlighted in yellow. Panel d shows degree distribution of network shown in panel c with fitted power law line.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3376453&req=5

f3: Gene Set Enrichment Analysis (GSEA).Panel a shows enrichment score (ES) distribution of all the enriched gene sets. Panel b shows variation of p value (Red) and q value (Blue) with Normalized Enrichment Score (NES). Please see text for detail. Panel c is a network of all core enriched genes of all the pathways taken together. Node size is a measure of Betweenness Centrality (BC). Larger is the size higher is the BC. Nodes with highest BC values are highlighted in yellow. Panel d shows degree distribution of network shown in panel c with fitted power law line.
Mentions: To identify pathways enriched in TIL4 treated samples over the samples treated with neutralizing antibodies, GSEA was performed on day 6transcription data. Results are shown in Table 5. Overview of GSEA analysis is illustrated in Figure 3a and b. Panel a shows distribution of enrichment score (ES) of all the gene sets enriched. On the X axis, gene sets that are present before “0” mark were overrepresented in the background set and those that are present after it were the sets enriched in the test set (TIL4 as opposed to TIL4ABS group). A dot plot of significance and Normalized Enrichment Score NES for is given in Figure 3b. This Figure (Figure 3b) shows that gene sets bearing NES, either less than -1 or more than +1 are significant at the cut off FDR q value of less than 25 %. Although in TIL4ABS samples, there were many gene sets with nominal p value less than 0.25, or even 0.05, but none of them was enriched at FDR q value of less than 0.25. The nominal p value is less relevant for comparing across the gene sets than FDR q value. Parameters used for the analysis are detailed in Methods section. Details on statistics used are described elsewhere17. As shown in Table 5 many pathways known to be associated with cytokine signaling were enriched in TCR + IL-4 treated sample. Enriched pathways can be classified under the heads of signaling pathways and metabolic pathways.

Bottom Line: In this study we show that IL-4 is crucial during reinforcement window of human Th2 differentiation for optimal Th2 development.We have also shown here that during this stage, IL-4 helps in cellular decision-making process of differentiation versus proliferation.This approach can be generalized to analyze "omics" data to identify key regulatory modules.

View Article: PubMed Central - PubMed

Affiliation: Immunology Group International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi-110067, India.

ABSTRACT
In this study we show that IL-4 is crucial during reinforcement window of human Th2 differentiation for optimal Th2 development. We have also shown here that during this stage, IL-4 helps in cellular decision-making process of differentiation versus proliferation. We have combined computational and experimental methods to analyze Th2 transcription network to name novel players of the process of Th2 differentiation. Here we report that LIF through STAT3 negatively regulates Th2 differentiation. This approach can be generalized to analyze "omics" data to identify key regulatory modules.

Show MeSH
Related in: MedlinePlus