Researchers who study complex human disease with genetic technologies are on the cusp of innovative science. To perform these cutting-edge experiments, they need to be able to use existing data resources to integrate genetic data from many sources. Interactive open-source tools that address this need allow researchers to answer key research questions and foster scientific discovery. The NIH Common Fund Data Ecosystem (CFDE), which aims to accelerate research by enabling the broad use of data generated across multiple Common Fund programs, is supporting research into the development of these interactive open-source tools.

With funding from CFDE, Avi Ma’ayan, Ph.D., and colleagues at the Icahn School of Medicine at Mount Sinai are working to make these tools a reality. They developed a new open-sourced web-based tool called GeneSetCart. GeneSetCart allows users to upload their own genetic datasets, compare and combine that data to make biological discoveries, and receive recommendations from a large-language model (LLM) that suggests possible alternative genes for analysis and experimentation. This tool simplifies the handling of sets of genes and proteins, including data from eight different NIH Common Fund supported programs. Dr. Ma’ayan and colleagues intend to add more NIH Common Fund dataset libraries to the tool as they are made available. 

To demonstrate the potential of GeneSetCart, Dr. Ma’ayan and colleagues used the tool to explore new genes and FDA approved drugs that may be relevant to Alexander disease. Alexander disease is a rare brain disorder that mostly impacts infants. It can cause seizures, developmental delays, fluid buildup in the brain, and other symptoms for which there is no cure. The tool allowed them to identify potential drug treatments to reverse the genetic impact of the disease. More work is needed to determine if these drugs are effective, but GeneSetCart helped researchers better understand the molecules involved in the disease and identify possible treatment options for further exploration. 

GeneSetCart helps researchers uncover scientific insights using small, tailored gene set collections. While it’s not suited for large-scale analyses and LLM-generated outputs require review, this feature helps researchers accelerate the discovery of genetic markers linked to disease, enabling more effective, personalized treatments. 

Dr. Ma’ayan’s team is one of ten research groups across the country that use data tools like GeneSetCart to tackle Alexander disease for possible treatments and cures. Read more about Alexander Disease and the role of artificial intelligence and data science: Dad Uses AI To Help Find Treatment For Son's Rare Disease. 

Reference:Marino GB, Olaiya S, Evangelista JE, Clarke DJB, Ma'ayan A. GeneSetCart: assembling, augmenting, combining, visualizing, and analyzing gene sets. Gigascience. 2025 Jan 6;14: giaf025. doi: 10.1093/gigascience/giaf025. PMID: 40208796.