Table 1.
Role in sepsis of the pathways for which gene ensemble noise associates positively (increases) with the disease states (healthy < early/survived < late/deceased).
| Pathways/Complexes | Role in sepsis pathology | References |
|---|---|---|
| KEGG: HIF-1 signalling pathway | Metabolic reprogramming of innate immune cells during the hyperinflammatory and immunotolerant phases of sepsis | 30,31 |
| KEGG: Peroxisome | Defective peroxisome recycling alters cellular redox homeostasis and leads to exaggerated oxidative stress response to endotoxin (infection) and sepsis | 32 |
| KEGG: Necroptosis | Necroptosis is implicated in pulmonary diseases and sepsis-associated organ injury | 33,34 |
| KEGG: NOD-like receptor signalling pathway | Activation of Toll-like and NOD-like receptor signalling protects mice from polymicrobial sepsis-associated lethality | 35 |
| KEGG: Fc epsilon RI signalling pathway | Fc receptors bind to antibodies attached to invading pathogens and their up-regulation can serve a potential biomarker for sepsis. Mice deficient for FCER1G gene encoding the γ-subunit of Fc epsilon RI show increased resistance to sepsis | 36,37 |
| KEGG: Autophagy—other | Autophagy is an adaptive protective process that eliminates damaged proteins, organelles and pathogens. It is thought to be a promising target in treatment of sepsis | 38 |
| KEGG: Biosynthesis of amino acids | Sepsis results in significant disorders in amino acids metabolism | 39 |
| KEGG: Glucagon signalling pathway | Glucagon levels negatively associate with clinical outcome in sepsis patients | 40 |
| KEGG: Propanoate (propionate) metabolism | Propionic acidaemia caused by altered propionate metabolism often results in sepsis and death | 41 |
| KEGG: Circadian rhythm | There is accumulating evidence for association between circadian misalignment and severity of inflammatory responses in sepsis | 42 |
| KEGG: Dopaminergic synapse | Dopamine mediates neuroimmune communications and dopaminergic is implicated in inflammation and sepsis | 43,44 |
| KEGG: Amyotrophic lateral sclerosis (ALS) | ALS patients often develop pulmonary insufficiency and have increased risk of sepsis | 45 |
| CORUM: Respiratory chain complex I, mitochondrial | Mitochondrial disfunction resulting in reduced respiratory chain complex I activity and low ATP levels is a whole mark for sepsis | 46 |
| KEGG: Osteoclast differentiation | Mean expression of osteoclast differentiation genes is up-regulated in human septic shock | 47 |
| KEGG: Tight junction | Sepsis disrupts intestinal barrier which leads to a multiple organ dysfunction syndrome and alters the expression of tight junction proteins | 48 |