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Table 1 Directed network analysis for the derived AOP network built in Cytoscape and analyzed using the NetworkAnalyzer plugin

From: Adverse outcome pathways as a tool for the design of testing strategies to support the safety assessment of emerging advanced materials at the nanoscale

NodeMIE / KE / AO# Shared AOPsBetweenness
In/Out Ratio
Increased, recruitment of pro-inflammatory cellsKE30.0882359541.25
Loss of alveolar membrane integrityKE30.1274518441
Increased secretion, pro-inflammatory mediatorsKE30.09188441
Increased ROS synthesisKE30.0543677340.75
Activation, T-helper type 2 cellsKE20.0570415230.666666667
Surfactant function inhibitionKE20.0325315321.5
ECM depositionKE20.0187175321.5
Fibroblast / myofibroblast proliferationKE20.0169345321.5
Increased, TFF2 releaseKE10.0053484130.333333333
Cellular toxicityKE10.0271843120.5
Activation, epithelial cellsKE10.0169343212
Destruction of ECM, proteinases and elastasesKE10.0106953212
Chronic inflammationKE10.0049023120.5
Increased, serum amyloid A expressionKE10.0320862111
Formation, serum amyloid A-high density lipoprotein complexKE10.0267382111
Reduced lung volumeKE10.0267382111
Increased, systemic cholesterolKE10.0196082111
Increased, DNA damage and mutationKE10.0160432111
Impaired oxygenationKE10.014262111
Foam cell formationKE10.0106952111
Increased, cell proliferationKE10.0089132111
Loss of proteinase / antiproteinase enzymatic balanceKE10.0066842111
Increased secretion, pro-inflammatory and pro-fibrotic mediatorsKE10.0062392111
Blood components leak into the lungsKE10.0053482111
Increased, IL-33 expressionKE10.0017832111
Lung fibrosisAO20220Undefined
Interaction with the lung resident cell membrane componentsMIE202020
Lung cancerAO10110Undefined
Plaque progressionAO10110Undefined
Acute inhalation toxicityAO10110Undefined
Lung emphysemaAO10110Undefined
Frustrated phagocytosisMIE101010
Interaction with resident cell membrane components TLR2/4 bindingMIE101010
Interaction with epithelial cell membraneMIE101010
Interaction with lung surfactantMIE101010
  1. Betweenness centrality reflects the amount of control a KE exerts on other KEs in the network, a higher number indicates greater degree of control (and greater network disruption if removed)
  2. MIE molecular initiating event, KE key event, AO adverse outcome