Table 6 Top biological pathways and terms identified by gene set analysis in the meta-analysis between heme-stimulated endothelial cells versus other gene expression studies in sickle cell disease.

From: Role of innate immunity-triggered pathways in the pathogenesis of Sickle Cell Disease: a meta-analysis of gene expression studies

Biological pathway

Library

Meta-analysis

Complement and coagulation cascades

KEGG

1, 2, 3

Cytokine cytokine receptor interaction

 

1, 2

Porphyrin and chlorophyll metabolism

 

3

Glutathione metabolism

 

3

Cell adhesion molecules

 

1

Interferon alpha/beta signaling

Reactome

1, 2, 3

Extracellular matrix organization

 

1, 2, 3

Cell surface interactions at the vascular wall

 

1

Synthesis of prostaglandins and thromboxanes

 

1, 3

Platelet degranulation

 

1, 3

VEGF binds to VEGFR

 

1, 3

Formation of Fibrin Clot

 

1

Heme Biosynthesis

Wiki

3

Oxidative Stress

 

2, 3

Transcriptional activation by NRF2

Pathways

2

Cytokines and inflammatory response

 

1

Gene ontology term

Library

Meta-analysis

Defense response to other organism

Gene ontology biological process

1, 3

Cellular response to type I interferon

1, 2, 3

Inflammatory response

1, 3

Regulation of angiogenesis

1,2, 3

Regulation of vasculature development

 

1, 3

Cellular response to cytokine stimulus

 

1, 3

Blood coagulation

 

1, 2

Platelet activation

 

1, 3

Regulation of cellular response to VEGF stimulus

 

1, 3

Regulation of vascular permeability

 

2

Regulation of cell adhesion

 

2

Positive regulation of vasodilation

 

3

Response to hypoxia

 

3

Cellular response to reactive oxygen species

 

3

Regulation of acute inflammatory response

 

3

NIK/NF-kappaB signaling

 

3

  1. GSA (gene set analysis) was performed using the EnrichR tool, that includes 69 different gene set libraries. Pathways or terms identified in the meta-analysis between heme-stimulated endothelial cells versus 3 additional gene expression studies involving SCD patient samples are presented. The meta-analysis compared heme-stimulated endothelial cells versus: (1) adults in steady-state; (2) pulmonary endothelial cells stimulated with plasma from patients with SCD during acute chest syndrome; and (3) children with SCD in acute crisis.