Identifying neuroinflammation in omics datasets with a computational biological network model of reactive astrogliosis

      Barkhuizen, M.; Mathis, C.; Peitsch, M. C.; Talikka, M.

      Conference date
      Jul 26, 2021
      Conference name
      Alzheimer's Association International Conference (AAIC) 2021

      Introduction • 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. Objectives 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.