ArticleNature communications2017
Identifying therapeutic targets by combining transcriptional data with ordinal clinical measurements.
Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
20 citing papers in PubMed, 29 citations in OpenAlex.
- An exploratory metabolomic comparison of participants with fast or absent functional progression from 2CARE, a randomized, double-blind clinical trial in Huntington's disease.Scientific reports · 2024Trial
- Proteo-Metabolomic Profiling of PMM2-CDG Reveals Dysregulation of Retinoic Acid Synthesis, Myo-Inositol, and the Hexosamine Pathway.Journal of inherited metabolic disease · 2026Article
- Fingolimod Effects on Motor Function and BDNF-TrkB Signaling in a Huntington's Mouse Model Are Disease-Stage-Dependent.International journal of molecular sciences · 2026Article
- Diet Driven Differences in Host Tolerance Are Linked to Shifts in Global Gene Expression in a Common Avian Host-Pathogen System.Molecular ecology · 2025Article
- Review
- Recent Insight into the Role of Sphingosine-1-Phosphate Lyase in Neurodegeneration.International journal of molecular sciences · 2023Review
- Treatment with THI, an inhibitor of sphingosine-1-phosphate lyase, modulates glycosphingolipid metabolism and results therapeutically effective in experimental models of Huntington's disease.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Role of sphingolipid metabolism in neurodegeneration.Journal of neurochemistry · 2021Review
- Preclinical and Clinical Evidence for the Involvement of Sphingosine 1-Phosphate Signaling in the Pathophysiology of Vascular Cognitive Impairment.Neuromolecular medicine · 2021Review
- A Rationale for Hypoxic and Chemical Conditioning in Huntington's Disease.International journal of molecular sciences · 2021Review
- Bioenergetic deficits in Huntington's disease iPSC-derived neural cells and rescue with glycolytic metabolites.Human molecular genetics · 2020Article
- The S1P-S1PR Axis in Neurological Disorders-Insights into Current and Future Therapeutic Perspectives.Cells · 2020Review
- A Multi-Omics Interpretable Machine Learning Model Reveals Modes of Action of Small Molecules.Scientific reports · 2020Article
- Gene Expression Predicts Histological Severity and Reveals Distinct Molecular Profiles of Nonalcoholic Fatty Liver Disease.Scientific reports · 2019Article
- The Role of Ceramide and Sphingosine-1-Phosphate in Alzheimer's Disease and Other Neurodegenerative Disorders.Molecular neurobiology · 2019Review
- Stimulation of Sphingosine Kinase 1 (SPHK1) Is Beneficial in a Huntington's Disease Pre-clinical Model.Frontiers in molecular neuroscience · 2019Article
- Sphingosine 1-Phosphate Receptors and Metabolic Enzymes as Druggable Targets for Brain Diseases.Frontiers in pharmacology · 2019Review
- Turning omics data into therapeutic insights.Current opinion in pharmacology · 2018Review
- Sphingolipid Metabolism: A New Therapeutic Opportunity for Brain Degenerative Disorders.Frontiers in neuroscience · 2018Review
- Article
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 1 country.
Funding
Abstract
The immense and growing repositories of transcriptional data may contain critical insights for developing new therapies. Current approaches to mining these data largely rely on binary classifications of disease vs. control, and are not able to incorporate measures of disease severity. We report an analytical approach to integrate ordinal clinical information with transcriptomics. We apply this method to public data for a large cohort of Huntington's disease patients and controls, identifying and prioritizing phenotype-associated genes. We verify the role of a high-ranked gene in dysregulation of sphingolipid metabolism in the disease and demonstrate that inhibiting the enzyme, sphingosine-1-phosphate lyase 1 (SPL), has neuroprotective effects in Huntington's disease models. Finally, we show that one consequence of inhibiting SPL is intracellular inhibition of histone deacetylases, thus linking our observations in sphingolipid metabolism to a well-characterized Huntington's disease pathway. Our approach is easily applied to any data with ordinal clinical measurements, and may deepen our understanding of disease processes.Identifying gene subsets affecting disease phenotypes from transcriptome data is challenge. Here, the authors develop a method that combines transcriptional data with disease ordinal clinical measurements to discover a sphingolipid metabolism regulator involving in Huntington's disease progression.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.