The eukaryotic promoter database in its 30th year: focus on non-vertebrate organisms

Dreos, René; Ambrosini, Giovanna; Groux, Romain; Périer, Rouaïda Cavin; Bücher, Philipp

doi:10.1093/nar/gkw1069

Cited by 246 publications

(272 citation statements)

References 23 publications

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“…CGI annotations were downloaded from the UCSC database (http://genome. ucsc.edu/index.html) and TSSs from the Eukaryotic Promoter Database (EPD: http: //epd.vital-it.ch/) (Dreos et al 2017) for human and mouse, and from the Ensembl website (http://www.ensembl.org/index.html) (Aken et al 2016) for chicken.…”

Section: Methodsmentioning

confidence: 99%

Evolution of Replication Origins in Vertebrate Genomes: Rapid Turnover Despite Selective Constraints

Massip

Laurent

Brossas

et al. 2018

Preprint

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Background:The replication programme of vertebrate genomes is driven by the chromosomal distribution and timing of activation of tens of thousands of replication origins. Genome-wide studies have shown the frequent association of origins with promoters and CpG islands, and their enrichment in G-quadruplex sequence motifs (G4). However, the genetic determinants driving their activity remain poorly understood. To gain insight on the functional constraints operating on replication origins and their spatial distribution, we conducted the first evolutionary comparison of genome-wide origins maps across vertebrates. Results:We generated a high resolution genome-wide map of chicken replication origins (the first of a bird genome), and performed an extensive comparison with human and mouse maps. The analysis of intra-species polymorphism revealed a strong depletion of genetic diversity on an ∼ 40 bp region centred on the replication initiation loci. Surprisingly, this depletion in genetic diversity was not linked to the presence of G4 motifs, nor to the association with promoters or CpG islands. In contrast, we also showed that origins experienced a rapid turnover during vertebrates evolution, since pairwise comparisons of origin maps revealed that only 4 to 24% of them were conserved between any two species. Conclusions:This study unravels the existence of a novel genetic determinant of replication origins, the precise functional role of which remains to be determined. Despite the importance of replication initiation activity for the fitness of organisms, the distribution of replication origins along vertebrate chromosomes is highly flexible.

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Section: Methodsmentioning

confidence: 99%

Evolution of Replication Origins in Vertebrate Genomes: Rapid Turnover Despite Selective Constraints

Massip

Laurent

Brossas

et al. 2018

Preprint

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“…Table 1A shows that multiple GWAS disease risk SNPs located within the glutamate receptor subnetwork can be annotated as enhancers associated with tobacco smoking status, chronic schizophrenia (ICD diagnostic code F20), and bipolar 1 disorder (ICD diagnostic codes F31.0 -F31.64). (37), column 6, enhancer status determined using annotation from (38,(48)(49)(50)(51)(52)(53)(54)(55)(56)(57)(58)(59)(60), and column 7 using Hi-C data from (46,61,62). eQTL data support the results shown in column 7 (63,64).…”

Section: Gwas Disease Risk Snps and Hi-c Loops Discriminate 2 Ketaminmentioning

confidence: 61%

Ketamine’s pharmacogenomic network in human brain contains sub-networks associated with glutamate neurotransmission and with neuroplasticity

Higgins

Handelman

Allyn-Feurer

et al. 2020

Preprint

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The pharmacogenomic network responsible for the rapid antidepressant action of ketamine and concomitant adverse events in patients has been poorly defined. Integrative, multiscale biological data analytics helps explain ketamine's action. Using a validated computational pipeline, candidate ketamine-response genes and regulatory RNAs from published literature, binding affinity studies, and single nucleotide polymorphisms (SNPs) from genomewide association studies (GWAS), we identified 108 SNPs associated with 110 genes and regulatory RNAs. All of these SNPs are classified as enhancers, and additional chromatin interaction mapping in human neural cell lines and tissue shows enhancer-promoter interactions involving other network members. Pathway analysis and gene set optimization identified three composite sub-networks within the broader ketamine pharmacogenomic network. Expression patterns of ketamine network genes within the postmortem human brain are concordant with ketamine neurocircuitry based on the results of 24 published functional neuroimaging studies. The ketamine pharmacogenomic network is enriched in forebrain regions known to be rapidly activated by ketamine, including cingulate cortex and frontal cortex, and is significantly regulated by ketamine (p=6.26E-33; Fisher's exact test). The ketamine pharmacogenomic network can be partitioned into distinct enhancer sub-networks associated with: (1) glutamate neurotransmission, chromatin remodeling, smoking behavior, schizophrenia, pain, nausea, vomiting, and post-operative delirium; (2) neuroplasticity, depression, and alcohol consumption; and (3) pharmacokinetics. The component sub-networks explain the diverse action mechanisms of ketamine and its analogs.These results may be useful for optimizing pharmacotherapy in patients diagnosed with depression, pain or related stress disorders. GRIA4 (12), and many other known (8,13) and unknown pharmacodynamic targets within human brain. Ketamine and its metabolites strongly induce the expression of the CYP2B6 gene in human brain, which encodes a drug metabolizing enzyme that contributes to first-and second-pass metabolism of the drug and its metabolites (14). Recent genomewide association studies (GWAS) in humans demonstrate association of ketamine response and adverse events with enhancers of genes and long non-coding RNAs (lncRNAs) related to the roundabout guidance receptor 2 (ROBO2) gene, whose product binds members of the slit guidance ligand family (SLIT1, SLIT2) that are involved in dendrite guidance and synaptic plasticity (15,16). Like phencyclidine, a structurally related compound, ketamine induces acute dissociation, with both drugs exhibiting species-specific differences in response. In sum, the central nervous system (CNS) pathway(s) responsible for the rapid antidepressant effects of ketamine and its enantiomers in patients diagnosed with treatment-resistant depression (TRD) remain poorly defined, including emergence of on-and off-target effects and individual differences in response and adverse eve...

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“…A variant could be assigned to one or more Ensembl genes based on SNPEff annotations splice_region_variant, start_loss, stop_gained, stop_lost, and stop_retained_variant mutations. We also included variants located within experimentally derived promoter regions and Ensembl-derived Tarbase miRNA binding sites; and regulatory variants located within 1000 bases of a particular gene, including ChIP-seq determined transcription factor binding sites (TFBS), and Ensembl-derived CTCF, TFBS, and promoter sites [ [44][45][46]. Group set variants were filtered by requiring either a FATHMM-XF score > 0.5 or a CDTS < 1% constrained region score [ 47,48 ].…”

Section: Statistical Analysesmentioning

confidence: 99%

Whole-Genome Association Analyses of Sleep-disordered Breathing Phenotypes in the NHLBI TOPMed Program

Cade

Lee

Sofer

et al. 2019

Preprint

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Sleep-disordered breathing (SDB) is a common disorder associated with significant morbidity. Through the NHLBI Trans-Omics for Precision Medicine (TOPMed) program we report the first whole-genome sequence analysis of SDB. We identified 4 rare gene-based associations with SDB traits in 7,988 individuals of diverse ancestry and 4 replicated common variant associations with inclusion of additional samples (n=13,257). We identified a multi-ethnic set-based rare-variant association (p = 3.48 × 10 -8 ) on chromosome X with ARMCX3.Transcription factor binding site enrichment identified associations with genes implicated with respiratory and craniofacial traits. Results highlighted associations in genes that modulate lung development, inflammation, respiratory rhythmogenesis and HIF1A-mediated hypoxic response.

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The eukaryotic promoter database in its 30th year: focus on non-vertebrate organisms

Cited by 246 publications

References 23 publications

Evolution of Replication Origins in Vertebrate Genomes: Rapid Turnover Despite Selective Constraints

Evolution of Replication Origins in Vertebrate Genomes: Rapid Turnover Despite Selective Constraints

Ketamine’s pharmacogenomic network in human brain contains sub-networks associated with glutamate neurotransmission and with neuroplasticity

Whole-Genome Association Analyses of Sleep-disordered Breathing Phenotypes in the NHLBI TOPMed Program

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