Alzheimer's disease (AD) is a common disease that is partly due to protein misfolding and aggregation. Research on AD is a national priority with 5.5 million Americans affected at an annual cost of more than $250 billion and no available cure. This is despite heavy investments in the collection of diverse clinical and biological data in experimental and population-based studies. Artificial intelligence (AI) and machine learning have the potential to reveal patterns in clinical and multi-source large-scale Alzheimer’s data that have not been found using standard approaches. We propose here a comprehensive biomedical computing and health informatics research project to develop and apply cutting-edge AI algorithms and biomedical software for the analysis of large- scale AD data. At the heart of this proposed informatics program is the PennAI method and software for automating machine learning through an AI algorithm that can learn from prior analyses. This approach takes the guesswork out of picking the right machine learning algorithms and parameter settings thus making this computing technology accessible to everyone. Specifically, we will develop three novel informatics methods to tailor PennAI to the analysis of AD data. First, we will develop a Multi-Modal Interaction (M2I) feature selection algorithm for identifying genetic interactions that are predictive of AD (AIM 1). Second, we will develop a Knowledge-driven Multi-omics Integration (KMI) algorithm for combining omics features for AI analysis of AD (AIM 2). Third, we will develop a Multidimensional Brain Imaging Omics (MBIO) integration framework for the joint analysis of multi-source large-scale data for predicting AD. Finally, we will integrate all three biomedical informatics methods into our open-source PennAI software package and apply it to two large population-based studies of AD. We expect PennAI will reveal new biomarkers for AD that will open the door for better treatments and clinical decision support.

There have been no new FDA-approved drugs for Alzheimer’s disease in more than 20 years. The goal of this project is to develop artificial intelligence (AI) approaches for extracting unforeseen patterns from clinical, genetic, genomic, and imaging data that could lead to ideas for new drug development. Our proposed AI methods and software will be open-source, user-friendly, and freely available for all to use.