Integrated network analysis of transcriptomic and proteomic data in psoriasis

Abstract

Background: Psoriasis is complex inflammatory skin pathology of autoimmune origin. Several cell types are perturbed in this pathology, and underlying signaling events are complex and still poorly understood.

Results: In order to gain insight into molecular machinery underlying the disease, we conducted a comprehensive meta-analysis of proteomics and transcriptomics of psoriatic lesions from independent studies. Network-based analysis revealed similarities in regulation at both proteomics and transcriptomics level. We identified a group of transcription factors responsible for overexpression of psoriasis genes and a number of previously unknown signaling pathways that may play a role in this process. We also evaluated functional synergy between transcriptomics and proteomics results.

Conclusions: We developed network-based methodology for integrative analysis of high throughput data sets of different types. Investigation of proteomics and transcriptomics data sets on psoriasis revealed versatility in regulatory machinery underlying pathology and showed complementarities between two levels of cellular organization.

Figure 1

Representative silver-stained 2DE gel images of lesional and uninvolved skin biopsy lysates. a) - gel image of lesional skin biopsy lysate; b) - gel image of uninvolved skin biopsy lysate. Spots corresponding to proteins overexpressed in lesions are marked with red rectangles and numbered. Spot 1 correspond to 3 proteins of keratin family, spot 2 - SCCA2, spot 3 - SCCA1, spot 4 - enolase 1, spot 5 - SOD2, spot 6 - galectin-7. S100A7 is found in spots 7 and 8 and S100A9 corresponds to 9^th and 10^th spots.

Figure 2

Network illustrating regulatory pathways leading to transcription activation of proteomics markers. Red circles denote upregulated proteins. Designations of network objects and interaction types can be found in Additional file 4.

Figure 3

Common transcriptional factors important for regulation of objects at both transcriptomics and proteomic levels. Objects in MetaCore database representing transcriptional factors found to be important regulators of pathology-related genes. Red circles denote that corresponding gene is upregulated in psoriatic lesion. Designations of network objects and interaction types can be found in Additional file 4.

Figure 4

Candidate receptors with their respective upregulated ligands. Initial steps of pathways presumably activated in lesions (ligands, overexpressed at transcriptional level and their corresponding receptors) Red circles denote that corresponding gene is upregulated in psoriatic lesion. Designations of network objects and interaction types can be found in Additional file 4.

Figure 5

Upregulated candidate receptors with their respective ligands. Initial steps of pathways presumably activated in lesions (receptors, overexpressed at transcriptional level and their corresponding ligands) Red circles denote that corresponding gene is upregulated in psoriatic lesion. Designations of network objects and interaction types can be found in Additional file 4.