Non-coding variants impactcis-regulatory coordination in a cell type-specific manner DOI Creative Commons
Olga Pushkarev, Guido van Mierlo, Judith F. Kribelbauer

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 11, 2023

Abstract BACKGROUND Interactions among cis -regulatory elements (CREs) play a crucial role in gene regulation. Various approaches have been developed to map these interactions genome-wide, including those relying on interindividual epigenomic variation identify groups of covariable regulatory elements, referred as chromatin modules (CMs). While CM mapping allows investigate the relationship between modularity and expression, computational principles used for identification vary their application outcomes. RESULTS We comprehensively evaluate streamline existing tools present guidelines optimal utilization epigenome data from diverse population individuals assess coordination across human genome. showcase effectiveness our recommended practices by analysing distinct cell types demonstrate type-specificity CRE CMs relevance expression. Integration genotype information revealed that many non-coding disease-associated variants affect activity type-specific manner affecting binding transcription factors. provide example cases illustrate detail how can be deconstruct GWAS loci, understand variable expression surface receptors immune cells reveal genetic impact prognostic markers chronic lymphocytic leukaemia. CONCLUSIONS Our study presents an strategy mapping, reveals capture CREs its Non-coding disrupt this coordination, we highlight may lead disease predisposition manner.

Language: Английский

Non-coding variants impact cis-regulatory coordination in a cell type-specific manner DOI Creative Commons
Olga Pushkarev, Guido van Mierlo, Judith F. Kribelbauer

et al.

Genome biology, Journal Year: 2024, Volume and Issue: 25(1)

Published: July 18, 2024

Abstract Background Interactions among cis -regulatory elements (CREs) play a crucial role in gene regulation. Various approaches have been developed to map these interactions genome-wide, including those relying on interindividual epigenomic variation identify groups of covariable regulatory elements, referred as chromatin modules (CMs). While CM mapping allows investigate the relationship between modularity and expression, computational principles used for identification vary their application outcomes. Results We comprehensively evaluate streamline existing tools present guidelines optimal utilization epigenome data from diverse population individuals assess coordination across human genome. showcase effectiveness our recommended practices by analyzing distinct cell types demonstrate type specificity CRE CMs relevance expression. Integration genotype information revealed that many non-coding disease-associated variants affect activity type-specific manner affecting binding transcription factors. provide example cases illustrate detail how can be deconstruct GWAS loci, variable expression surface receptors immune cells, reveal genetic impact prognostic markers chronic lymphocytic leukemia. Conclusions Our study presents an strategy reveals capture CREs its Non-coding disrupt this coordination, we highlight may lead disease predisposition manner.

Language: Английский

Citations

2
Identifying genetic variants associated with chromatin looping and genome function DOI Creative Commons
Sourya Bhattacharyya, Ferhat Ay

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Sept. 18, 2024

Abstract Here we present a comprehensive HiChIP dataset on naïve CD4 T cells (nCD4) from 30 donors and identify QTLs that associate with genotype-dependent and/or allele-specific variation of contacts defining loops between active regulatory regions (iQTLs). We observe substantial overlap iQTLs previously defined eQTLs histone QTLs, an enrichment for fine-mapped GWAS variants. Furthermore, describe distinct subset nCD4 iQTLs, which the significant chromatin in are translated into eQTL trends cell memory subsets. Finally, define connectivity-QTLs as significantly associated concordant changes over broad genomic region (e.g., SNP RNASET2 locus). Our results demonstrate importance complementary modality QTL mapping their power identifying uncharacterized linked to cell-specific gene expression connectivity.

Language: Английский

Citations

2
Non-coding variants impactcis-regulatory coordination in a cell type-specific manner DOI Creative Commons
Olga Pushkarev, Guido van Mierlo, Judith F. Kribelbauer

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 11, 2023

Abstract BACKGROUND Interactions among cis -regulatory elements (CREs) play a crucial role in gene regulation. Various approaches have been developed to map these interactions genome-wide, including those relying on interindividual epigenomic variation identify groups of covariable regulatory elements, referred as chromatin modules (CMs). While CM mapping allows investigate the relationship between modularity and expression, computational principles used for identification vary their application outcomes. RESULTS We comprehensively evaluate streamline existing tools present guidelines optimal utilization epigenome data from diverse population individuals assess coordination across human genome. showcase effectiveness our recommended practices by analysing distinct cell types demonstrate type-specificity CRE CMs relevance expression. Integration genotype information revealed that many non-coding disease-associated variants affect activity type-specific manner affecting binding transcription factors. provide example cases illustrate detail how can be deconstruct GWAS loci, understand variable expression surface receptors immune cells reveal genetic impact prognostic markers chronic lymphocytic leukaemia. CONCLUSIONS Our study presents an strategy mapping, reveals capture CREs its Non-coding disrupt this coordination, we highlight may lead disease predisposition manner.

Language: Английский

Citations

0