Figure 1.
Work flow of gene expression analysis.
The figure represents scheme of extraction of differentially expressed genes (up regulated: 420, down regulated: 308) from the raw microarray data.
Figure 2.
Hierarchical clustering of gene expression data obtained from acclimatized controls (CN) and HAPE (PE) individuals.
Hierarchical clustering distinctly separated the two groups of individuals (CN and PE) indicating unique gene expression signatures. Expression values of specific genes are represented by color intensities shown in the reference color key.
Figure 3.
Comparison of relative expression (log2 values) of selected genes obtained by microarray and real time PCR experiments (TLDA).
17 out of 20 genes show similarity of trend on both the platforms.
Figure 4.
Clustering of GO terms related to biological processes.
GO terms were clustered utilizing software BINGO and individual clusters indicated as shown in the figure.
Table 1.
KEGG Pathway-specific gene transcripts in HAPE data set (Extracted from DAVID Bioinformatics Resource).
Figure 5.
The figure represents an integrated network of multiple pathways interacting through common gene products. Specific sub-networks (gene associations within individual pathways) constituting the integrated network are highlighted in Supplementary Figure S3 (A-R). The major sub-network pathways include regulation of actin cytoskeleton, calcium signaling, MAPK pathway, immune cell signaling, cell-cell communication, VEGF signaling amongst others. The network shown was extracted from the list of differentially expressed genes utilizing ‘Pathway Miner’. Relationships between the genes (nodes connected by edges) suggest co-occurrence in a biological pathway. Weight of a specific edge is a relative representation of the number of pathways in which the associating nodes (gene products) co-occur in the KEGG pathway resource. The nodes are labeled by gene names and colored based on the respective fold changes for specific genes in the original data set.
Table 2.
Genes involved in early responses to hypoxia.
Figure 6.
Schematic representation of possible events occurring during HAPE.
The pathways suggested by the current data set have been integrated with established phenomenon such as pulmonary vasoconstriction, elevated pulmonary artery pressure which are known to precede HAPE. Perturbation of pathways such as those regulating vasoconstriction, inflammation, gap junctions and adhesion molecules can dysregulate vascular homeostasis leading to fluid leak and edema formation.