| Domain | Preferred concept / identifier | Suggested ontology terms / codes | Practical note |
|---|---|---|---|
| Disease | Sepsis | **MeSH:** Sepsis (D018805); **ICD-10-CM:** A41.9, Sepsis, unspecified organism; **ICD-11 candidates:** 1G40, sepsis without septic shock; 1G41, sepsis with septic shock; **MONDO:** general sepsis identifier requires release-level verification | Sepsis is infection-associated, life-threatening organ dysfunction caused by a dysregulated host response; do not equate it with uncomplicated infection, bacteremia, or SIRS (pqac-00000001, pqac-00000017). |
| Disease subtype | Bacterial infectious disease with sepsis | **MONDO:** MONDO:0005229 (verified in retrieved Open Targets mapping) | A narrower concept than all-cause sepsis; sepsis may also be viral, fungal, or parasitic (pqac-00000007). |
| Disease subtype | Infectious disease with sepsis | **MONDO:** MONDO:1040015 (verified in retrieved Open Targets mapping) | Broad infection-with-sepsis concept found in Open Targets; confirm intended hierarchy before production use (pqac-00000007). |
| Disease severity | Septic shock | **ICD-10-CM:** R65.21; **ICD-11 candidate:** 1G41; **SNOMED CT:** use current-release “Septic shock” concept | Clinical subset with vasopressor-dependent hypotension and elevated lactate despite adequate volume resuscitation; substantially higher mortality than sepsis without shock (pqac-00000001, pqac-00000018). |
| Phenotype | Fever or hypothermia | **HPO:** Fever (HP:0001945); Hypothermia (HP:0002045) | Variable and episodic acute signs; absence of fever does not exclude sepsis. Temperature responses depend on host age, severity, and environment (pqac-00000001, pqac-00000011). |
| Phenotype | Tachycardia and hypotension | **HPO:** Tachycardia (HP:0001649); Hypotension (HP:0002615) | Cardiovascular manifestations range from compensated tachycardia to vasoplegia, myocardial depression, and shock (pqac-00000010). |
| Phenotype | Tachypnea, hypoxemia, respiratory failure | **HPO:** Tachypnea (HP:0002789); Hypoxemia (HP:0012418); Respiratory failure (term; verify current HPO identifier) | Alveolar–capillary injury causes noncardiogenic edema, impaired compliance, and reduced gas exchange; respiratory dysfunction commonly contributes to SOFA-defined sepsis (pqac-00000000, pqac-00000010). |
| Phenotype | Altered consciousness, delirium, encephalopathy | **HPO:** Delirium (HP:0031258); Encephalopathy (HP:0001298); Altered mental status (term; verify current HPO identifier) | May be an early sign or sepsis-associated encephalopathy; exclude CNS infection, structural lesions, drugs, metabolic disease, and primary neurologic causes (pqac-00000010). |
| Phenotype | Oliguria and acute kidney injury | **HPO:** Oliguria (HP:0100520); Acute kidney injury (term; verify current HPO identifier) | Dynamic organ dysfunction assessed using urine output and creatinine; may require renal replacement therapy in severe cases (pqac-00000010, pqac-00000039). |
| Phenotype | Thrombocytopenia and coagulopathy | **HPO:** Thrombocytopenia (HP:0001873); Abnormality of coagulation (HP:0001928); Disseminated intravascular coagulation (term; verify current HPO identifier) | Reflects platelet consumption, coagulation activation, endothelial injury, and—in severe disease—DIC (pqac-00000010, pqac-00000011). |
| Phenotype | Hyperbilirubinemia and hepatic dysfunction | **HPO:** Hyperbilirubinemia (HP:0002904); Abnormal liver function (term; verify current HPO identifier) | SOFA hepatic dysfunction is bilirubin-based; mechanisms include cholestasis, inflammation, hypoxia, and shock (pqac-00000010). |
| Laboratory phenotype | Hyperlactatemia | **HPO:** Increased circulating lactate concentration (term; verify current HPO identifier); **LOINC:** use specimen/method-specific lactate code | Lactate supports severity assessment and resuscitation monitoring but is neither sepsis-specific nor a pure measure of tissue hypoxia (pqac-00000018, pqac-00000019). |
| Organ | Lung | **UBERON:** lung (UBERON:0002048) | Frequent infection source and target of secondary injury; manifestations include pneumonia, hypoxemia, and ARDS (pqac-00000000, pqac-00000010). |
| Organ | Kidney | **UBERON:** kidney (UBERON:0002113) | Sepsis-associated AKI involves microcirculatory, inflammatory, endothelial, and metabolic injury rather than hypoperfusion alone (pqac-00000010). |
| Organ | Liver | **UBERON:** liver (UBERON:0002107) | Hepatic dysfunction may present with cholestasis, hyperbilirubinemia, impaired clearance, or hypoxic hepatitis (pqac-00000010). |
| Organ | Heart | **UBERON:** heart (UBERON:0000948) | Sepsis-induced cardiomyopathy can affect both ventricles; mild troponin elevation is common but nonspecific (pqac-00000010). |
| Organ | Brain | **UBERON:** brain (UBERON:0000955) | Neuroinflammation, blood–brain-barrier dysfunction, microglial activation, and systemic metabolic disturbances contribute to encephalopathy and long-term cognitive deficits (pqac-00000001, pqac-00000010). |
| System/tissue | Blood and vascular endothelium | **UBERON:** blood (UBERON:0000178); vasculature (term; verify site-specific UBERON code) | Endothelial activation converts an anticoagulant surface into a proadhesive, procoagulant interface and promotes capillary leak and immunothrombosis (pqac-00000010). |
| Cell type | Neutrophil | **CL:** neutrophil (CL:0000775) | Performs phagocytosis and NET formation; dysregulated NETs trap pathogens but can damage endothelium and amplify thrombosis and inflammation (pqac-00000009, pqac-00000011). |
| Cell type | Monocyte | **CL:** monocyte (CL:0000576) | Key pathogen-sensing and antigen-presenting cell; reduced monocyte HLA-DR is used experimentally to define sepsis-induced immunoparalysis (pqac-00000008, pqac-00000040). |
| Cell type | Macrophage | **CL:** macrophage (CL:0000235) | Produces inflammatory cytokines after PRR activation; later polarization and uptake of apoptotic cells can increase IL-10 and TGF-β and suppress immunity (pqac-00000008, pqac-00000009). |
| Cell type | Dendritic cell | **CL:** dendritic cell (CL:0000451) | Apoptotic depletion and impaired antigen presentation contribute to immunosuppression (pqac-00000008). |
| Cell type | T lymphocyte | **CL:** T cell (CL:0000084) | Lymphopenia, apoptosis, PD-1 expression, TH2/regulatory skewing, and functional exhaustion are associated with persistent immune dysfunction (pqac-00000008). |
| Cell type | B lymphocyte | **CL:** B cell (CL:0000236) | Sepsis-associated apoptosis reduces adaptive immune-cell numbers and may impair subsequent antimicrobial immunity (pqac-00000008). |
| Cell type | Platelet | **CL:** platelet (CL:0000233) | Platelets link coagulation to innate immunity through fibrin binding, P-selectin-mediated leukocyte recruitment, and microthrombus formation (pqac-00000010). |
| Cell type | Endothelial cell | **CL:** endothelial cell (CL:0000115) | Central effector of permeability, leukocyte adhesion, vasoplegia, coagulation activation, and microvascular organ injury (pqac-00000009, pqac-00000010). |
| Mechanism | Pattern-recognition receptor signaling | **GO-BP:** innate immune response (GO:0045087); inflammatory response (GO:0006954); Toll-like receptor signaling pathway (GO:0002224) | PAMPs and DAMPs activate TLRs, NOD proteins, dectins, RAGE, and RNA sensors, converging on NF-κB, AP-1, and IRFs (pqac-00000008). |
| Mechanism | Cytokine production and signaling | **GO-BP:** cytokine-mediated signaling pathway (GO:0019221); positive regulation of cytokine production (GO:0001819) | TNF, IL-1, IL-6, chemokines, and interferons drive systemic inflammation, while IL-10 and TGF-β contribute to compensatory immunosuppression (pqac-00000008, pqac-00000011). |
| Mechanism | Complement activation | **GO-BP:** complement activation (GO:0006956) | C3a, C4a, and particularly C5a amplify inflammation, alter neutrophil function, and can promote immune-cell apoptosis (pqac-00000009, pqac-00000014). |
| Mechanism | Coagulation and immunothrombosis | **GO-BP:** blood coagulation (GO:0007596); platelet activation (GO:0030168) | Inflammation, endothelial activation, platelets, fibrin, and leukocytes generate microvascular thrombi; excessive activation may progress to consumptive coagulopathy or DIC (pqac-00000010, pqac-00000011). |
| Mechanism | Programmed cell death | **GO-BP:** apoptotic process (GO:0006915); pyroptosis (GO:0070269) | Human autopsy and experimental evidence support lymphocyte and dendritic-cell apoptosis as drivers of immunosuppression; pyroptosis is a plausible inflammatory mechanism but requires evidence-specific annotation (pqac-00000008). |
| Mechanism | Neutrophil extracellular-trap formation | **GO-BP:** neutrophil extracellular trap formation (GO:0140725) | NETs support antimicrobial defense but expose histones and proteases that injure endothelium and amplify cytokine signaling (pqac-00000009). |
| Mechanism | Mitochondrial/metabolic dysfunction | **GO-BP:** cellular response to oxidative stress (GO:0034599); cellular respiration (GO:0045333); **GO-CC:** mitochondrion (GO:0005739) | Bioenergetic failure, oxidative stress, and metabolic reprogramming may cause organ dysfunction despite restored macrocirculation; many candidate signatures remain investigational (pqac-00000012, pqac-00000035). |
| Mechanism | Immune suppression/exhaustion | **GO-BP:** negative regulation of immune response (GO:0050777); regulation of T-cell apoptotic process (suggested term) | PD-1/PD-L1 signaling, reduced MHC-II/HLA-DR, lymphocyte apoptosis, impaired cytokine production, and regulatory-cell expansion can coexist with inflammation (pqac-00000008). |
| Subcellular site | Plasma membrane and extracellular compartment | **GO-CC:** plasma membrane (GO:0005886); extracellular region (GO:0005576) | PRRs, adhesion molecules, complement, cytokines, coagulation proteins, and NET components act across these compartments (pqac-00000008, pqac-00000009, pqac-00000010). |
| Chemical | Lipopolysaccharide | **ChEBI:** lipopolysaccharide (CHEBI:16412) | Gram-negative PAMP and experimental endotoxemia trigger; LPS models are reproducible but do not reproduce live, heterogeneous human infection (pqac-00000029, pqac-00000030). |
| Chemical/biomarker | Lactate | **ChEBI:** lactate (CHEBI:24996) | Measure specimen-specific blood lactate clinically; elevation has multiple causes, including adrenergic glycolysis, impaired clearance, and hypoperfusion (pqac-00000018, pqac-00000019). |
| Chemical/intervention | Norepinephrine | **ChEBI:** noradrenaline (CHEBI:18357); **NCIt suggested term:** Norepinephrine | Preferred first-line vasopressor in septic shock; receptor-target associations in Open Targets reflect therapeutic biology rather than causal sepsis genes (pqac-00000007, pqac-00000019). |
| Chemical/intervention | Vasopressin | **ChEBI:** vasopressin (verify current ChEBI identifier); **NCIt suggested term:** Vasopressin | Common adjunct to norepinephrine when escalating vasopressor support; not a pathogen-directed therapy (pqac-00000018, pqac-00000019). |
| Chemical/intervention | Hydrocortisone | **ChEBI:** hydrocortisone (CHEBI:17650); **NCIt suggested term:** Hydrocortisone | Suggested for septic shock with an ongoing vasopressor requirement; annotate as adjunctive corticosteroid therapy, not general sepsis monotherapy (pqac-00000019). |
| Intervention | Broad-spectrum antimicrobial therapy | **NCIt suggested terms:** Antibiotic Therapy; Anti-Infective Therapy; Antimicrobial Treatment | Start promptly after appropriate cultures when this does not cause harmful delay; select empirically by source, resistance risk, prior exposure, and local ecology, then de-escalate when possible (pqac-00000015). |
| Intervention | Source control | **NCIt suggested terms:** Surgical Procedure; Drainage Procedure; Device Removal | Drain infected collections, debride necrotic tissue, relieve obstruction, or remove infected devices as soon as medically and logistically practical (pqac-00000015). |
| Intervention | Intravenous crystalloid resuscitation | **NCIt suggested terms:** Fluid Therapy; Intravenous Infusion; Crystalloid Solution | Initial resuscitation is individualized; balanced crystalloids are generally preferred, and repeated reassessment is needed to avoid fluid accumulation and organ edema (pqac-00000019). |
| Intervention | Vasopressor therapy | **NCIt suggested terms:** Vasopressor Therapy; Norepinephrine Therapy | Used to restore perfusion pressure when hypotension persists during/after initial fluid resuscitation; peripheral initiation may avoid harmful delay while central access is arranged (pqac-00000019). |
| Intervention | Mechanical ventilation / ARDS care | **NCIt suggested terms:** Mechanical Ventilation; Lung Protective Ventilation | Use lung-protective ventilation for sepsis-associated ARDS; ventilatory support treats organ failure but not the infectious trigger (pqac-00000010, pqac-00000019). |
| Intervention | Renal replacement therapy | **NCIt suggested term:** Renal Replacement Therapy | Reserved for standard urgent indications or severe persistent AKI; trials evaluate need and timing as outcomes rather than establishing sepsis-specific dialysis criteria (pqac-00000019, pqac-00000039). |
| Intervention | Post-sepsis rehabilitation and follow-up | **NCIt suggested terms:** Rehabilitation; Physical Therapy; Occupational Therapy; Cognitive Assessment | Assess physical, cognitive, emotional, medication, social, and economic needs after discharge; long-term disability and failure to return to work are common (pqac-00000003, pqac-00000005). |


*Table: Compact knowledge-base mappings for sepsis disease concepts, phenotypes, anatomy, cells, mechanisms, chemicals, and interventions. Verified identifiers are distinguished from suggested terms or codes requiring release-level validation.*