ArticleNature communications2019
Quantitating the epigenetic transformation contributing to cholesterol homeostasis using Gaussian process.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- Codon-optimizedMolecular therapy. Nucleic acids · 2026Article
- Alpha-1 antitrypsin deficiency: genetics, clinical manifestations, AI prognostics, and advanced imaging in liver disease.Annals of medicine and surgery (2012) · 2025Review
- Exploration of Bromodomain Proteins as Drug Targets for Niemann-Pick Type C Disease.International journal of molecular sciences · 2025Article
- Spatial covariance reveals isothiocyanate natural products adjust redox stress to restore function in alpha-1-antitrypsin deficiency.Cell reports. Medicine · 2025Article
- Mutant induced neurons and humanized mice enable identification of Niemann-Pick type C1 proteostatic therapies.JCI insight · 2024Article
- COPII cage assembly factor Sec13 integrates information flow regulating endomembrane function in response to human variation.Scientific reports · 2024Article
- Tracing genetic diversity captures the molecular basis of misfolding disease.Nature communications · 2024Article
- Advances in research on potential therapeutic approaches for Niemann-Pick C1 disease.Frontiers in pharmacology · 2024Review
- MicroRNA Profile, Putative Diagnostic Biomarkers and RNA-Based Therapies in the Inherited Lipid Storage Disease Niemann-Pick Type C.Biomedicines · 2023Review
- Understanding the host-pathogen evolutionary balance through Gaussian process modeling of SARS-CoV-2.Patterns (New York, N.Y.) · 2023Article
- Capturing the conversion of the pathogenic alpha-1-antitrypsin fold by ATF6 enhanced proteostasis.Cell chemical biology · 2023Article
- Species-specific differences in NPC1 protein trafficking govern therapeutic response in Niemann-Pick type C disease.JCI insight · 2022Article
- Triangulating variation in the population to define mechanisms for precision management of genetic disease.Structure (London, England : 1993) · 2022Article
- Spatial covariance analysis reveals the residue-by-residue thermodynamic contribution of variation to the CFTR fold.Communications biology · 2022Article
- AI in health and medicine.Nature medicine · 2022Review
- Leveraging Population Genomics for Individualized Correction of the Hallmarks of Alpha-1 Antitrypsin Deficiency.Chronic obstructive pulmonary diseases (Miami, Fla.) · 2020Review
- TRANSPIRE: A Computational Pipeline to Elucidate Intracellular Protein Movements from Spatial Proteomics Data Sets.Journal of the American Society for Mass Spectrometry · 2020Article
- Correction of Niemann-Pick type C1 trafficking and activity with the histone deacetylase inhibitor valproic acid.The Journal of biological chemistry · 2020Article
- Cholesterol Transport in Wild-Type NPC1 and P691S: Molecular Dynamics Simulations Reveal Changes in Dynamical Behavior.International journal of molecular sciences · 2020Article
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
To understand the impact of epigenetics on human misfolding disease, we apply Gaussian-process regression (GPR) based machine learning (ML) (GPR-ML) through variation spatial profiling (VSP). VSP generates population-based matrices describing the spatial covariance (SCV) relationships that link genetic diversity to fitness of the individual in response to histone deacetylases inhibitors (HDACi). Niemann-Pick C1 (NPC1) is a Mendelian disorder caused by >300 variants in the NPC1 gene that disrupt cholesterol homeostasis leading to the rapid onset and progression of neurodegenerative disease. We determine the sequence-to-function-to-structure relationships of the NPC1 polypeptide fold required for membrane trafficking and generation of a tunnel that mediates cholesterol flux in late endosomal/lysosomal (LE/Ly) compartments. HDACi treatment reveals unanticipated epigenomic plasticity in SCV relationships that restore NPC1 functionality. GPR-ML based matrices capture the epigenetic processes impacting information flow through central dogma, providing a framework for quantifying the effect of the environment on the healthspan of the individual.
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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.