MOSES: a methylation-based gene association approach for unveiling environmentally regulated genes linked to a trait or disease DOI Creative Commons
Soyeon Kim,

Yidi Qin,

Hyun Jung Park

et al.

Clinical Epigenetics, Journal Year: 2024, Volume and Issue: 16(1)

Published: Nov. 18, 2024

DNA methylation is a critical regulatory mechanism of gene expression, influencing various human diseases and traits. While traditional expression quantitative trait loci (eQTL) studies have helped elucidate the genetic regulation there growing need to explore environmental influences on expression. Existing methods such as PrediXcan FUSION focus genotype-based associations but overlook impact factors. To address this gap, we present MOSES (methylation-based association), novel approach that utilizes identify environmentally regulated genes associated with traits or without relying measured involves training, imputation, association testing. It employs elastic-net penalized regression models estimate influence CpGs SNPs (if available) We developed compared four versions incorporating different data: (1) cis-DNA within 1 Mb promoter regions, (2) both cis-SNPs cis-CpGs, 3) cis- part trans- (±5Mb away) from regions), 4) long-range (±10 regions. Our analysis using nasal epithelium white blood cell data Epigenetic Variation Childhood Asthma in Puerto Ricans (EVA-PR) study demonstrated MOSES, particularly version (MOSES-DNAm 10 M), significantly outperformed existing like PrediXcan, MethylXcan, Biomethyl predicting MOSES-DNAm M identified more differentially expressed (DEGs) atopic asthma, those involved immune pathways, highlighting its superior performance uncovering genes. Further application lung tissue idiopathic pulmonary fibrosis (IPF) patients confirmed robustness versatility across tissues. represents an innovative advancement studies, leveraging capture factors By CpGs, provides predictive accuracy capabilities methods. This offers valuable insights into complex interplay between genetics environment, enhancing our understanding disease mechanisms potentially guiding therapeutic strategies. The user-friendly R package publicly available advance diseases, including immune-related conditions asthma.

Language: Английский

Mechanisms and technologies in cancer epigenetics DOI Creative Commons
Zaki A. Sherif, Olorunseun O. Ogunwobi, Habtom W. Ressom

et al.

Frontiers in Oncology, Journal Year: 2025, Volume and Issue: 14

Published: Jan. 7, 2025

Cancer's epigenetic landscape, a labyrinthine tapestry of molecular modifications, has long captivated researchers with its profound influence on gene expression and cellular fate. This review discusses the intricate mechanisms underlying cancer epigenetics, unraveling complex interplay between DNA methylation, histone chromatin remodeling, non-coding RNAs. We navigate through tumultuous seas dysregulation, exploring how these processes conspire to silence tumor suppressors unleash oncogenic potential. The narrative pivots cutting-edge technologies, revolutionizing our ability decode epigenome. From granular insights single-cell epigenomics holistic view offered by multi-omics approaches, we examine tools are reshaping understanding heterogeneity evolution. also highlights emerging techniques, such as spatial long-read sequencing, which promise unveil hidden dimensions regulation. Finally, probed transformative potential CRISPR-based epigenome editing computational analysis transmute raw data into biological insights. study seeks synthesize comprehensive yet nuanced contemporary landscape future directions research.

Language: Английский

Citations

0
DNA methylation as a contributor to dysregulation of STX6 and other frontotemporal lobar degeneration genetic risk-associated loci DOI Creative Commons
Naiomi Rambarack, Katherine Fodder, Megha Murthy

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 21, 2025

Frontotemporal Lobar Degeneration (FTLD) represents a spectrum of clinically, genetically, and pathologically heterogeneous neurodegenerative disorders characterised by progressive atrophy the frontal temporal lobes brain. The two major FTLD pathological subgroups are FTLD-TDP FTLD-tau. While majority cases sporadic, heterogeneity also exists within familial cases, typically involving mutations in MAPT, GRN or C9orf72, which is not fully explained known genetic mechanisms. We sought to address this gap investigating effect epigenetic modifications, specifically DNA methylation variation, on genes associated with risk different subtypes. compiled list using text-mining databases literature searches. Frontal cortex profiles were derived from three datasets containing FTLD-tau: FTLD1m (N = 23) type A C9orf72 mutation carriers TDP Type C sporadic FTLD2m 48) FTLD-Tau MAPT carriers, B FTLD3m 163) supranuclear palsy (PSP) corresponding controls. To investigate downstream effects further, we then leveraged transcriptomic proteomic for controls examine gene protein expression levels. Our analysis revealed shared promoter region hypomethylation STX6 across FTLD-tau subtypes, though largest size was observed PSP compared (delta-beta -32%, adjusted-p value=0.002). dysregulation Additionally, performed detailed examination subtypes without presence nominally significant differentially methylated CpGs variable positions genes, often unique patterns consequences gene/protein carriers. highlight contribution at regions regulating previously FTLD, including STX6. analysed relationship mechanism increase our understanding how these mechanisms interact FTLD.

Language: Английский

Citations

0
Features That Distinguish Age-Related Macular Degeneration from Aging DOI
Dorota Skowronska‐Krawczyk, Silvia C. Finnemann, Maria B. Grant

et al.

Experimental Eye Research, Journal Year: 2025, Volume and Issue: 254, P. 110303 - 110303

Published: Feb. 20, 2025

Language: Английский

Citations

0
Integrative genome-wide aberrant DNA methylation and transcriptome analysis identifies diagnostic markers for colorectal cancer DOI

Hengyang Shen,

Zhenling Wang, Yang Chen

et al.

Archives of Toxicology, Journal Year: 2025, Volume and Issue: unknown

Published: March 10, 2025

Language: Английский

Citations

0
Using Genomics to Develop Personalized Cardiovascular Treatments DOI
Mihir M. Sanghvi, William J. Young, Hafiz Naderi

et al.

Arteriosclerosis Thrombosis and Vascular Biology, Journal Year: 2025, Volume and Issue: unknown

Published: April 17, 2025

Advances in genomic technologies have significantly enhanced our understanding of both monogenic and polygenic etiologies cardiovascular disease. In this review, we explore how the utilization information is bringing personalized medicine approaches to forefront disease management. We discuss data can resolve diagnostic uncertainty, support cascade screening, inform treatment strategies. The role that genome-wide association studies had identifying thousands risk variants for diseases, these insights, harnessed through development scores, could advance prediction beyond traditional clinical algorithms. detail pharmacogenomics leverage genotype guide drug selection mitigate adverse events. Finally, present paradigm-shifting approach gene therapy, which holds promise being a curative intervention conditions.

Language: Английский

Citations

0
Cell-type specific epigenetic clocks to quantify biological age at cell-type resolution DOI Creative Commons
Huige Tong, Xiaolong Guo, Macsue Jacques

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 31, 2024

The ability to accurately quantify biological age could help monitor and control healthy aging. Epigenetic clocks have emerged as promising tools for estimating age, yet they been developed from heterogeneous bulk tissues, are thus composites of two aging processes, one reflecting the change cell-type composition with another individual cell-types. There is a need dissect these components epigenetic clocks, develop that can yield estimates at resolution. Here we demonstrate in blood brain, approximately 39% 12% an accuracy driven by underlying shifts lymphocyte neuronal subsets, respectively. Using brain liver tissue prototypes, build validate neuron hepatocyte specific DNA methylation improved chronological corresponding cell tissue-types. We find glia display acceleration Alzheimers Disease effect being strongest temporal lobe. Moreover, CpGs small but significant overlap causal DamAge-clock, mapping key genes implicated neurodegeneration. clock found accelerated under various pathological conditions. In contrast, non-cell-type do not age-acceleration, or only so marginally. summary, this work highlights importance dissecting quantifying

Language: Английский

Citations

2
Cell-type specific epigenetic clocks to quantify biological age at cell-type resolution DOI Creative Commons
Huige Tong, Xiaolong Guo, Macsue Jacques

et al.

Aging, Journal Year: 2024, Volume and Issue: 16(22), P. 13452 - 13504

Published: Dec. 29, 2024

The ability to accurately quantify biological age could help monitor and control healthy aging. Epigenetic clocks have emerged as promising tools for estimating age, yet they been developed from heterogeneous bulk tissues, are thus composites of two aging processes, one reflecting the change cell-type composition with another individual cell-types. There is a need dissect these components epigenetic clocks, develop that can yield estimates at resolution. Here we demonstrate in blood brain, approximately 39% 12% an clock's accuracy driven by underlying shifts lymphocyte neuronal subsets, respectively. Using brain liver tissue prototypes, build validate neuron hepatocyte specific DNA methylation improved chronological corresponding cell tissue-types. We find glia display acceleration Alzheimer's Disease effect being strongest temporal lobe. Moreover, CpGs small but significant overlap causal DamAge-clock, mapping key genes implicated neurodegeneration. clock found accelerated under various pathological conditions. In contrast, non-cell-type do not age-acceleration, or only so marginally. summary, this work highlights importance dissecting quantifying

Language: Английский

Citations

2
Epigenetics and aging: relevance for sleep medicine DOI
Rene Cortese

Current Opinion in Pulmonary Medicine, Journal Year: 2024, Volume and Issue: unknown

Published: July 31, 2024

Sleep disorders encompass a wide range of conditions with substantial individual variability. Epigenetics, the study heritable changes beyond DNA sequence, offers promising avenue for personalized medicine in this field.

Language: Английский

Citations

1
Integrating Genetic Insights, Technological Advancements, Screening, and Personalized Pharmacological Interventions in Childhood Obesity DOI Creative Commons
Robert Šket, Barbara Slapnik, Primož Kotnik

et al.

Advances in Therapy, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 13, 2024

Childhood obesity is a significant global health challenge with rising prevalence over the past 50 years, affecting both immediate and long-term outcomes. The increase in from 0.7% to 5.6% girls 0.9% 7.8% boys highlights urgency of addressing this epidemic. By 2025, it estimated that 206 million children adolescents aged 5-19 years will be living obesity. This review explores complex interplay genomics genetics pediatric obesity, transitioning monogenic polygenic epigenetics, incorporating advancements omics technologies. evolutionary purpose adiposity, systemic evaluation hyperphagia, role various genetic factors are discussed. Technological genotyping offer new insights interventions. integration screening into clinical practice for early identification personalized treatment strategies emphasized.

Language: Английский

Citations

1
MOSES: a methylation-based gene association approach for unveiling environmentally regulated genes linked to a trait or disease DOI Creative Commons
Soyeon Kim,

Yidi Qin,

Hyun Jung Park

et al.

Clinical Epigenetics, Journal Year: 2024, Volume and Issue: 16(1)

Published: Nov. 18, 2024

DNA methylation is a critical regulatory mechanism of gene expression, influencing various human diseases and traits. While traditional expression quantitative trait loci (eQTL) studies have helped elucidate the genetic regulation there growing need to explore environmental influences on expression. Existing methods such as PrediXcan FUSION focus genotype-based associations but overlook impact factors. To address this gap, we present MOSES (methylation-based association), novel approach that utilizes identify environmentally regulated genes associated with traits or without relying measured involves training, imputation, association testing. It employs elastic-net penalized regression models estimate influence CpGs SNPs (if available) We developed compared four versions incorporating different data: (1) cis-DNA within 1 Mb promoter regions, (2) both cis-SNPs cis-CpGs, 3) cis- part trans- (±5Mb away) from regions), 4) long-range (±10 regions. Our analysis using nasal epithelium white blood cell data Epigenetic Variation Childhood Asthma in Puerto Ricans (EVA-PR) study demonstrated MOSES, particularly version (MOSES-DNAm 10 M), significantly outperformed existing like PrediXcan, MethylXcan, Biomethyl predicting MOSES-DNAm M identified more differentially expressed (DEGs) atopic asthma, those involved immune pathways, highlighting its superior performance uncovering genes. Further application lung tissue idiopathic pulmonary fibrosis (IPF) patients confirmed robustness versatility across tissues. represents an innovative advancement studies, leveraging capture factors By CpGs, provides predictive accuracy capabilities methods. This offers valuable insights into complex interplay between genetics environment, enhancing our understanding disease mechanisms potentially guiding therapeutic strategies. The user-friendly R package publicly available advance diseases, including immune-related conditions asthma.

Language: Английский

Citations

0