Alzheimer’s disease is complex. It involves many genes that can heighten the risk of developing the disease. There are currently no reliable treatments to prevent or slow its progression.
TREAT-AD (TaRget Enablement to Accelerate Therapy Development for AD) is a National Institutes of Health (NIH)–funded venture comprising two centers. The Alzheimer’s Disease Drug Discovery Center (AD3C), led by IU School of Medicine in partnership with Purdue University, aims to address challenges in discovering new therapeutic targets and drugs for the disease and to accelerate development of promising new treatments.
We spoke with Associate Director Robert Quick about the Cyberinfrastructure Integration Research Center’s (CIRC’s) involvement in TREAT-AD.
PTI: How is CIRC a part of this project?
Robert Quick: The NIH has an open science mission, which means they encourage sharing information that advances research into prevention, treatments, and cures. So, the drug discovery center needs a way to share its data, methods, and tools with researchers from academia, nonprofit research organizations, biotech, and the pharmaceutical industry for use in drug discovery and basic biology research.
As part of the AD3C Bioinformatics and Computational Biology (BCB) Core, CIRC staff are leading development of an open access data sharing platform called the BCB portal. The portal establishes an infrastructure for curating, processing, analyzing, visualizing, and sharing data; develops new data integration methods for predicting and prioritizing druggable targets; and provides bioinformatics data processing and analysis support for the entire project.
PTI: Why is CIRC’s involvement crucial?
Quick: Drug discovery research is critical to the future of Alzheimer’s and other diseases. Few projects I’ve worked on have the potential for immediate, real-world impact like TREAT-AD. In the BCB portal, we’re giving researchers easy access to what they need for this research. The idea is to pull all of these various Alzheimer’s disease–related tools and data together behind a single gateway interface.
Integrating the various researcher-designed applications, externally and internally hosted data sources, campus and national cyberinfrastructure compute resources, diverse visualization tools, and a uniform presentation layer into a well maintained and operated science gateway environment creates a powerful research tool for Alzheimer’s disease researchers. The BCB portal plays a critical role in providing a virtual environment for researchers within the AD3C collaboration, as well as external researchers who want to leverage the software, data, and research products the center produces.
PTI: What tools and data will be available through the BCB portal?
Quick: The core components of the BCB will bring together in one place open source, researcher-created analysis software; openly available public data sets and locally hosted experimental and clinical data sources; national, local, and cloud computing resources; and data management and sharing functionality.
Examples of the tools that will be available through the portal include Alzheimer’s Disease Explorer, an integrated bioinformatics platform that provides bioinformatics support; Biolearns, a cloud-based online learning portal; TSUNAMI, a bioinformatics tool suite for gene co-expression network mining; and the Top-down mass spectrometry based Proteoform Identification and Characterization (TopPIC) Suite, which provides several applications for mass spectrometry data analysis for public use.
PTI: What’s the software framework for the portal?
Quick: The BCB portal runs on Apache Airavata. Airavata enables users to compose, manage, execute, and monitor large-scale application executions and workflows on distributed computing resources. We made this choice based on the strength and history of Airavata in providing similar gateway services and on the local support and hosting provided by CIRC. Airvata also provides a uniform web interface for the multiple projects, which is important for new or external researchers to get the full benefits of an end-to-end data sharing platform.
PTI: What are CIRC’s future plans for supporting Alzheimer’s research?
Quick: We’re in year two of five, and we’re really beginning to understand the complexity. We’ll be expanding the public data portal to support the other TREAT-AD center, the Emory-Sage-Structural Genomics Consortium, to avoid confusion that could result from presenting the same or similar data in two different interfaces.
We’re also revisiting the workflow between the structural biology, medicinal chemistry, and high throughput screening groups. One thing we’ve heard repeatedly is that the structural biologists and medicinal chemists speak a different language. They’d like to find a mutually agreeable format so that when they find a target, both can easily understand its promising aspects, as well as potential pitfalls. Just because medicinal chemists see promise in a drug, that doesn’t necessarily mean the biologists will agree with this assessment. Communication among these groups is important, and we want to provide a format for documentation where everyone can quickly determine whether a drug is a target for additional research efforts.