Enrichr: a comprehensive gene set enrichment analysis web server 2016 update

Kuleshov, Maxim V.; Jones, Matthew R.; Rouillard, Andrew D.; Fernandez, Nicolas; Duan, Qiaonan; Wang, Zichen; Koplev, Simon; Jenkins, Sherry L.; Jagodnik, Kathleen M.; Lachmann, Alexander; McDermott, Michael G.; Monteiro, Caroline D.; Gundersen, Gregory W.; Ma’ayan, Avi

doi:10.1093/nar/gkw377

Cited by 7,794 publications

(7,343 citation statements)

References 41 publications

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“…Three hundred seventy‐five such genes were analyzed for enrichment using EnrichR, a collection of distinct gene set libraries (Kuleshov et al., 2016) (Figure S2). CheA library compared existing ChIP‐Seq data sets with our list of genes and identified binding sites for PPAR, LXR, and their heterodimer partner RXR significantly enriched in our gene set.…”

Section: Resultsmentioning

confidence: 99%

Changes at the nuclear lamina alter binding of pioneer factor Foxa2 in aged liver

et al. 2018

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SummaryIncreasing evidence suggests that regulation of heterochromatin at the nuclear envelope underlies metabolic disease susceptibility and age‐dependent metabolic changes, but the mechanism is unknown. Here, we profile lamina‐associated domains (LADs) using lamin B1 ChIP‐Seq in young and old hepatocytes and find that, although lamin B1 resides at a large fraction of domains at both ages, a third of lamin B1‐associated regions are bound exclusively at each age in vivo. Regions occupied by lamin B1 solely in young livers are enriched for the forkhead motif, bound by Foxa pioneer factors. We also show that Foxa2 binds more sites in Zmpste24 mutant mice, a progeroid laminopathy model, similar to increased Foxa2 occupancy in old livers. Aged and Zmpste24‐deficient livers share several features, including nuclear lamina abnormalities, increased Foxa2 binding, de‐repression of PPAR‐ and LXR‐dependent gene expression, and fatty liver. In old livers, additional Foxa2 binding is correlated to loss of lamin B1 and heterochromatin (H3K9me3 occupancy) at these loci. Our observations suggest that changes at the nuclear lamina are linked to altered Foxa2 binding, enabling opening of chromatin and de‐repression of genes encoding lipid synthesis and storage targets that contribute to etiology of hepatic steatosis.

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Section: Resultsmentioning

confidence: 99%

Changes at the nuclear lamina alter binding of pioneer factor Foxa2 in aged liver

et al. 2018

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“…For each disease, we included SNPs with a P < 5 × 10 −4 , and excluded SNPs in the MHC region due to the long stretches of LD in this region. We also performed a pathway analysis looking at KEGG pathways using enrichr38, 39 in order to compare results.…”

Section: Methodsmentioning

confidence: 99%

Genomics implicates adaptive and innate immunity in Alzheimer's and Parkinson's diseases

Gagliano

Pouget

Hardy

et al. 2016

Ann Clin Transl Neurol

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ObjectivesWe assessed the current genetic evidence for the involvement of various cell types and tissue types in the etiology of neurodegenerative diseases, especially in relation to the neuroinflammatory hypothesis of neurodegenerative diseases.MethodsWe obtained large‐scale genome‐wide association study (GWAS) summary statistics from Parkinson's disease (PD), Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS). We used multiple sclerosis (MS), an autoimmune disease of the central nervous system, as a positive control. We applied stratified LD score regression to determine if functional marks for cell type and tissue activity, and gene‐set lists were enriched for genetic heritability. We compared our results to those from two gene‐set enrichment methods (Ingenuity Pathway Analysis and enrichr).ResultsThere were no significant heritability enrichments for annotations marking genes active within brain regions, but there were significant heritability enrichments for annotations marking genes active within cell types that form part of both the innate and adaptive immune systems. We found this for MS (as expected) and also for AD and PD. The strongest signals were from the adaptive immune system (e.g., T cells) for PD, and from both the adaptive (e.g., T cells) and innate (e.g., CD14: a marker for monocytes, and CD15: a marker for neutrophils) immune systems for AD. Annotations from the liver were also significant for AD. Pathway analysis provided complementary results.InterpretationFor AD and PD, we found significant enrichment of heritability in annotations marking gene activity in immune cells.

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“…Alternatively, selection in these lineages may have targeted different genes involved in similar biological processes. Therefore, we performed a KEGG pathway analysis 41 of thylacine and canid positively selected genes using Enrichr 42 . We identified one pathway, inflammatory mediator regulation of TRP channels (hsa04750), among the top terms in both canids and the thylacine (Supplementary Tables 19 and 20).…”

Section: Nature Ecology and Evolutionmentioning

confidence: 99%

Genome of the Tasmanian tiger provides insights into the evolution and demography of an extinct marsupial carnivore

et al. 2017

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The Tasmanian tiger or thylacine (Thylacinus cynocephalus) was the largest carnivorous Australian marsupial to survive into the modern era. Despite last sharing a common ancestor with the eutherian canids ~160 million years ago, their phenotypic resemblance is considered the most striking example of convergent evolution in mammals. The last known thylacine died in captivity in 1936 and many aspects of the evolutionary history of this unique marsupial apex predator remain unknown. Here we have sequenced the genome of a preserved thylacine pouch young specimen to clarify the phylogenetic position of the thylacine within the carnivorous marsupials, reconstruct its historical demography and examine the genetic basis of its convergence with canids. Retroposon insertion patterns placed the thylacine as the basal lineage in Dasyuromorphia and suggest incomplete lineage sorting in early dasyuromorphs. Demographic analysis indicated a long-term decline in genetic diversity starting well before the arrival of humans in Australia. In spite of their extraordinary phenotypic convergence, comparative genomic analyses demonstrated that amino acid homoplasies between the thylacine and canids are largely consistent with neutral evolution. Furthermore, the genes and pathways targeted by positive selection differ markedly between these species. Together, these findings support models of adaptive convergence driven primarily by cis-regulatory evolution.

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Enrichr: a comprehensive gene set enrichment analysis web server 2016 update

Cited by 7,794 publications

References 41 publications

Changes at the nuclear lamina alter binding of pioneer factor Foxa2 in aged liver

Changes at the nuclear lamina alter binding of pioneer factor Foxa2 in aged liver

Genomics implicates adaptive and innate immunity in Alzheimer's and Parkinson's diseases

Genome of the Tasmanian tiger provides insights into the evolution and demography of an extinct marsupial carnivore

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