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Updated: May 18, 2026
Using Human Differentially Expressed Gene Lists to Perform Downstream Pathway Enrichment Analysis and Target Prioritization
Published on: October 3, 2025
GeneFriends: an online co-expression analysis tool to identify novel gene targets for aging and complex diseases
Sipko van Dam1, Rui Cordeiro, Thomas Craig
1Integrative Genomics of Ageing Group, Institute of Integrative Biology, University of Liverpool, Liverpool, L69 7ZB, UK.
Background:
Although many diseases have been well characterized at the molecular level, the underlying mechanisms are often unknown. Nearly half of all human genes remain poorly studied, yet these genes may contribute to a number of disease processes. Genes involved in common biological processes and diseases are often co-expressed. Using known disease-associated genes in a co-expression analysis may help identify and prioritize novel candidate genes for further study.
Results:
We have created an online tool, called GeneFriends, which identifies co-expressed genes in over 1,000 mouse microarray datasets. GeneFriends can be used to assign putative functions to poorly studied genes. Using a seed list of disease-associated genes and a guilt-by-association method, GeneFriends allows users to quickly identify novel genes and transcription factors associated with a disease or process. We tested GeneFriends using seed lists for aging, cancer, and mitochondrial complex I disease. We identified several candidate genes that have previously been predicted as relevant targets. Some of the genes identified are already being tested in clinical trials, indicating the effectiveness of this approach. Co-expressed transcription factors were investigated, identifying C/ebp genes as candidate regulators of aging. Furthermore, several novel candidate genes, that may be suitable for experimental or clinical follow-up, were identified. Two of the novel candidates of unknown function that were co-expressed with cancer-associated genes were selected for experimental validation. Knock-down of their human homologs (C1ORF112 and C12ORF48) in HeLa cells slowed growth, indicating that these genes of unknown function, identified by GeneFriends, may be involved in cancer.
Conclusions:
GeneFriends is a resource for biologists to identify and prioritize novel candidate genes involved in biological processes and complex diseases. It is an intuitive online resource that will help drive experimentation. GeneFriends is available online at: http://genefriends.org/.
Insights
GeneFriends identifies novel disease-associated genes using co-expression analysis. This tool helps prioritize candidate genes for further study in aging, cancer, and other complex diseases.
Area of Science:
- Genomics
- Bioinformatics
- Molecular Biology
Background:
- Many diseases lack understanding at the molecular level, with numerous genes poorly studied but potentially disease-relevant.
- Co-expression analysis of known disease genes can identify novel candidates for complex diseases.
Purpose of the Study:
- To develop and validate an online tool, GeneFriends, for identifying co-expressed genes associated with diseases.
- To facilitate the discovery and prioritization of novel candidate genes and transcription factors for biological research.
Main Methods:
- Created GeneFriends, an online tool analyzing over 1,000 mouse microarray datasets for gene co-expression.
- Employed a guilt-by-association method using seed lists of disease-associated genes.
- Validated candidate genes through experimental testing, including gene knockdown in human cell lines.
Main Results:
- GeneFriends identified relevant candidate genes for aging, cancer, and mitochondrial complex I disease.
- Some identified genes are already in clinical trials; C/ebp genes were implicated in aging regulation.
- Experimental validation confirmed two novel cancer-associated genes (C1ORF112, C12ORF48) are involved in cell growth.
Conclusions:
- GeneFriends serves as a valuable resource for discovering and prioritizing novel candidate genes in biological processes and diseases.
- The tool aids in driving experimental research by providing an intuitive platform for gene discovery.
- GeneFriends is accessible online at http://genefriends.org/.
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