ArticleFrontiers in immunology2021
Genetic Prioritization, Therapeutic Repositioning and Cross-Disease Comparisons Reveal Inflammatory Targets Tractable for Kidney Stone Disease.
Article in Frontiers in immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 11 citations in OpenAlex.
- Machine learning and 4D-LFQ quantitative proteomic analysis explore the molecular mechanism of kidney stone formation.Heliyon · 2024Article
- A cross-disease, pleiotropy-driven approach for therapeutic target prioritization and evaluation.Cell reports methods · 2024Article
- Priority index for critical Covid-19 identifies clinically actionable targets and drugs.Communications biology · 2024Article
- Inflammation-associated ectopic mineralization.Fundamental research · 2023Review
- OpenXGR: a web-server update for genomic summary data interpretation.Nucleic acids research · 2023Article
- PiER: web-based facilities tailored for genetic target prioritisation harnessing human disease genetics, functional genomics and protein interactions.Nucleic acids research · 2022Article
- Genomic Evidence Supports the Recognition of Endometriosis as an Inflammatory Systemic Disease and Reveals Disease-Specific Therapeutic Potentials of Targeting Neutrophil Degranulation.Frontiers in immunology · 2022Article
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Authors and funding
2 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background: Formation of kidney stones resulting in urological disorders remains a major cause of morbidity in renal diseases and many others. Innate immunity, mainly inflammasome, has demonstrated a key role in the development of kidney stone disease (or "nephrolithiasis"), but a molecular rationale for therapeutic intervention targeting immunity is far from clear. We reason that identifying inflammatory gene networks underlying disease risk would inform immunotherapeutic targets for candidate drug discovery. Results: We generated an atlas of genetic target prioritization, with the top targets highly enriched for genes involved in the NF-kB regulation, including interaction neighbors of inflammasome genes. We identified a network of highly ranked and interconnecting genes that are of functional relevance to nephrolithiasis and mediate crosstalk between inflammatory pathways. Crosstalk genes can be utilized for therapeutic repositioning, as highlighted by identification of ulixertinib and losmapimod that are both under clinical investigation as inhibitors of inflammatory mediators. Finally, we performed cross-disease comparisons and druggable pocket predictions, identifying inflammatory targets that are specific to and tractable for nephrolithiasis. Conclusion: Genetic targets and candidate drugs,
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