Identifying neuroinflammation in omics datasets with a computational biological network model of reactive astrogliosis
• Reactive astrogliosis is a change in the molecular phenotype of astrocytes in CNS injuries and diseases, including neurodegenerative diseases such as Alzheimer’s disease .
• Signaling changes in reactive astrogliosis are heterogeneous and correspond to specific injuries.
• Neuroinflammation (and neurodegenerative diseases) induces a neurotoxic "A1" phenotype, and ischemic stroke induces a protective "A2" phenotype.
• There is a core set of pan-reactive genes that are regulated by both inflammation and ischemia.
• Transcriptomics allows us to capture large-scale changes in gene expression in different disease states; but gaining mechanistic understanding is challenging.
• Here, we present a new tool for interpreting transcriptomic data within the context of reactive astrogliosis.
To construct causal biological network (CBN) models for interpreting astrogliosis transcriptomic data, which can:
• Facilitate comparison of the extent of reactive astrogliosis between different conditions in a dataset .
• Identify key molecular drivers of reactive astrogliosis in the dataset to aid mechanistic interpretation and help identify disease-specific reactive astrogliosis states.