Sage Bionetworks announces the launch of the Agora platform (agora.ampadportal.org) an interactive, web-based tool that allows researchers to explore curated genomic analyses of Alzheimer’s Disease (AD), including a list of early candidate target nominations for AD. The analyses accessible through Agora represent the culmination of over five years of research from the dozens of scientists that are part of the NIH-led Accelerating Medicines Partnership – Alzheimer’s Disease (AMP-AD) Target Discovery and Preclinical Validation Project. AMP-AD is a precompetitive public private partnership led by NIH’s National Institute on Aging (NIA) and managed by the Foundation for the NIH (FNIH), bringing together the government, industry and non-profit sectors to transform the way disease-relevant therapeutic targets are discovered and validated.
The AMP-AD program has generated a wealth of genomic, RNA expression, proteomic, and metabolomic data from over 3000 human brain and plasma samples collected in several NIA-supported AD cohorts and brain banks. The raw and processed data have been made widely accessible to qualified researchers through the AMP-AD Knowledge Portal. The datasets available through the Knowledge Portal have been used by the AMP-AD consortia members to produce hundreds of novel scientific research papers. In addition to AMP-AD investigators, external researchers have benefitted from the data sharing policy mandating rapid and broad sharing of data and have made critical new observations, including a recently published study that highlighted a previously uncharacterized relationship of human herpes virus with AD.
Although use of primary data is typically limited to investigators with bioinformatic expertise, AMP-AD investigators have also generated analyses that should be useful to a broader set of researchers. The launch of the Agora portal represents the first time that the analyses have been shared outside of the AMP-AD consortia members, which should enable additional groundbreaking discoveries.
“Agora enables researchers to leverage AMP-AD analyses to advance their own scientific questions,” says Ben Logsdon, Director of Neurodegenerative Disease Research at Sage Bionetworks and the lead investigator on the Agora project. “These results were developed to answer questions posed by AMP-AD researchers, but they are broadly useful. Agora provides an easy tool to enable the exploration and reuse of these results by anyone.”
“The most exciting results featured in this early release of Agora is the AMP-AD nominated targets list – a set of genes and proteins derived from unbiased computational analyses of rich human multi-omics data,” said Suzana Petanceska, Ph.D., Program Director at the NIA, overseeing the AMP-AD Target Discovery Consortium. “These molecular signals could illuminate new disease biology or serve as novel therapeutic targets, she explained. “We are purposely releasing them at an early stage of the target evaluation process to allow us to integrate the input of external researchers and to crowdsource the follow-on evaluation,” added Petanceska.
“Because AMP-AD operates under open science principles, researchers rapidly disclose data and results and, in turn, they receive early peer review to help guide research decisions,” said Lara Mangravite, President of Sage Bionetworks and an AMP-AD Principal Investigator. “Agora extends this approach so that external investigators can get actively involved in evaluation of the AMP-AD targets as well as further their own research by evaluating the performance of their genes of interest against multiple computational meta-analyses.”
“AMP-AD is a clear response to the National Plan to Address Alzheimer’s Disease,” said Eliezer Masliah, M.D., director of the Division of Neuroscience at NIA. “It is enabling precision medicine and facilitating the principles of open science and rapid dissemination of new targets with more shots on goal for AD.”
Agora will be frequently updated to incorporate the latest analyses from AMP-AD and its affiliate AD consortia. The initial release includes differential expression and co-expression network meta-analyses across four human RNA-sequence data sets. Future releases will expand to include human proteomic and metabolomic analyses, comparative evaluations of disease signatures across species, and integration of druggability and tractability information to guide selection of targets for early drug discovery. Analyses developed within other consortia in the NIA’s AD Translational Research portfolio including MODEL-AD, M2OVE-AD, and AD Resilience will also be integrated into future iterations.