Microphysiological systems to Advance Precision medicine for Alzheimer's Disease and Related Dementias (MAP-AD)

PROJECT ABSTRACT/SUMMARY Bioinformatics and Computational Biology Core (BCB) Alzheimer’s disease (AD) affects about 40 million people worldwide today and is the most common form of dementia found predominantly in the elderly. AD is a highly heterogeneous disease with major symptoms including progressive memory and cognitive domain deterioration over years, which eventually leads to death about 3-9 years after diagnosis. During the past few decades, many hypotheses have been proposed as potential mechanisms for AD, which involve multiple biological processes such as proteopathogenesis, mitochondrial abnormality, viral infection, and other glia cell-mediated immunological responses. However, the disease etiology and mechanisms still remain unclear, and currently, there is still no curative treatment for AD. During the past years, multiple endeavors have been taken by the AD research community to identify potential drug targets and large amount of data have been generated which enable mining for evidence for drug targets. As part of the Indiana University Microphysiological System for Alzheimer’s Disease (IU MAP-AD) Center, the Bioinformatics and Computational Biology Core (BCB Core) will play a critical role. Specifically, the BCB Core will implement advanced bioinformatics and imaging data processing and analysis pipelines for the data generated for the MPS models to be developed by the MMDV Core of the center. The analysis results will provide quantitative characterization of the models, which will be linked to public and disease phenotypic data to establish and validate the relevance of the models to AD or ADRD phenotypes. The data analysis pipelines will be driven by advanced AI and machine learning methods to enable effective integration of multi-scale and multi-modal data. Based on these pipelines and methods, the BCB core will collaborate with the PES Core to quantitatively characterize the changes in the models associated with various treatments and identify biomarkers for predicting the treatment effects. Last but not the least, the BCB Core will provide biostatistics design and bioinformatics data analysis support for the entire center covering the lifecycle of the MPS model development and validation by closely collaborating and coordinating with other cores for the MPS-AD Center. The BCB core will maintain frequent interactions with the rest of the center and also actively communicate with the consortium as well as the AD Knowledge Portal maintained by Sage Bionetworks for data standards, data and tool sharing, and best practices for data analysis and dissemination.