clusterProfiler 4.0: A universal enrichment tool for interpreting omics data
2021/07/01 by Tianzhi Wu, Erqiang Hu, Shuangbin Xu +11 · 215 citations
Biochemistry, Genetics and Molecular Biology · #Bioinformatics and Genomic Networks #Metabolomics and Mass Spectrometry Studies #Microbial Metabolic Engineering and Bioproduction
paper · doi:10.1016/j.xinn.2021.100141
openalex publication_date 2021/07/01 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/30
Abstract
Functional enrichment analysis is pivotal for interpreting high-throughput omics data in life science. It is crucial for this type of tool to use the latest annotation databases for as many organisms as possible. To meet these requirements, we present here an updated version of our popular Bioconductor package, clusterProfiler 4.0. This package has been enhanced considerably compared with its original version published 9 years ago. The new version provides a universal interface for functional enrichment analysis in thousands of organisms based on internally supported ontologies and pathways as well as annotation data provided by users or derived from online databases. It also extends the dplyr and ggplot2 packages to offer tidy interfaces for data operation and visualization. Other new features include gene set enrichment analysis and comparison of enrichment results from multiple gene lists. We anticipate that clusterProfiler 4.0 will be applied to a wide range of scenarios across diverse organisms.
Cited by
- Palmitic Acid Upregulates Type I Interferon–Mediated Antiviral Response and Cholesterol Biosynthesis in Human Astrocytes
- Circadian oscillations in chromatin accessibility systematically orchestrate rhythmic gene transcription in soybean
- Immunoglobulin M regulates airway hyperresponsiveness independent of T helper 2 allergic inflammation
- Bigger is better: modern <i>Cannabis</i> trichomes are larger and more productive than their landrace ancestors
- Whole-Genome Sequence of <i>Potamopyrgus antipodarum</i> —A Model System for the Maintenance of Sexual Reproduction—Reveals a Recent Whole-Genome Duplication
- Resolving the Stasis-Dynamism Paradox: Genome Evolution in Tree Ferns
- Nerve-associated macrophages control adipose homeostasis across lifespan and restrain age-related inflammation
- Hepatitis B virus is a stealth virus that minimizes proteomic and secretomic changes in primary human hepatocytes
- Adaptive radiation and social evolution of the ants
- APOE genotype determines cell-type-specific pathological landscape of Alzheimer’s disease
- Tumor-associated neutrophils attenuate the immunosensitivity of hepatocellular carcinoma
- Pericancerous cross-presentation to cytotoxic T lymphocytes impairs immunotherapeutic efficacy in hepatocellular carcinoma
- Cactus: A user-friendly and reproducible ATAC-Seq and mRNA-Seq analysis pipeline for data preprocessing, differential analysis, and enrichment analysis
- The chromosome‐level genome of <i>Hemiboea subcapitata</i> provides new insights into karst adaptation
- Cataloguing the postnatal small intestinal transcriptome during the first postnatal month
- Multi-omics identifies key genetic and metabolic networks regulating spike organ development in wheat
- PCK1 inhibits cGAS-STING activation by consumption of GTP to promote tumor immune evasion
- Multilevel Proteomics Reveals Epigenetic Signatures in BCG-Mediated Macrophage Activation
- Daya Cerna Lemak Pakan pada Avam Broiler setelah Pemberian Perasan Buah Pare (Momordica charantia L.)
- The variegated <i>canalized-1</i> tomato mutant is linked to photosystem assembly
- The <i>Silene latifolia</i> genome and its giant Y chromosome
- Extracellular vesicles released by senescent myoblasts affect recipient cells via miRNA-target interactions
- Dynamic chromatin regulatory programs of sucrose and citric acid metabolism during fruit ripening in <i>Citrus</i>
- Chromosome‐level genome of the green odorous frog ( <i>Odorrana margaretae</i> ) provides insights into the evolution of transposable elements and olfaction‐related gene families in frogs
- Neuroligin-2 is ubiquitinated by Nedd4l to control developmental astrocyte morphogenesis
- MAIT cells protect against sterile lung injury
- Multi-tissue transcriptomic aging atlas reveals predictive aging biomarkers in the killifish
- Novel targets to overcome antiangiogenesis therapy resistance in glioblastoma multiforme: Systems biology approach and suggestion of therapy by galunisertib
- Evolutionary conservation and divergence of phagocytic and coagulation programs across bilaterian circulating immune cells
- Laboratory mice engrafted with natural gut microbiota possess a wildling-like phenotype
- Gelada genomes highlight events of gene flow, hybridisation and local adaptation that track past climatic changes
- Chromosome-level genome assemblies and genetic maps reveal heterochiasmy and macrosynteny in endangered Atlantic Acropora
- Pharmacological CDK4/6 inhibition promotes vulnerability to lysosomotropic agents in breast cancer
- Next-Generation Sequencing Technology: Current Trends and Advancements
- Somatic cancer variants enriched in Alzheimer’s disease microglia-like cells drive inflammatory and proliferative states
- Cytoplasmic localization of pseudouridine synthase 7 facilitates a pseudouridine-dependent enhancement of cellular stress tolerance
- Population and single‐cell analyses reveal immune cell‐specific expression profiles associated with Alzheimer's disease risk
- Loss of angiopoietin-2 leads to region-specific brain malformations and blood-brain barrier leakage
- Inheritance of Material Wealth in a Natural Population
- Candida auris skin tropism and antifungal resistance are mediated by carbonic anhydrase Nce103
- Bile acids regulate lipid metabolism through selective actions on fatty acid absorption
- The PbrMADS1–PbrMYB169 complex has uniquely emerged to regulate lignification of stone cells in pear
- PBMCpedia: a harmonized PBMC scRNA-seq database with unified mapping and enhanced celltype annotation
- Genomic insights into chromosomal fusion and its evolutionary implications for zokors
- Modulation of the leaf transcriptome of <i>Quercus robur</i> by specialist and generalist herbivorous insects
- Single-cell analyses of tissue regeneration in two true jellyfish
- AI-assisted systems pharmacology with experimental validation reveal multi-target anticancer mechanisms of <i>Ganoderma lucidum</i> extracts against lung cancer
- Acute exercise rewires the proteomic landscape of human immune cells
- Body-wide multi-omic counteraction of aging with GLP-1R agonism
- CESA7 and microtubules pattern complex secondary cell walls in explosive fruit of <i>Cardamine hirsuta</i>
- A chromosome-level <i>Mitragyna parvifolia</i> genome unveils spirooxindole alkaloid diversification and mitraphylline biosynthesis
- Host-Associated Genetic Differentiation in the Face of Ongoing Gene Flow: Ecological Speciation in a Pathogenic Parasite of Freshwater Fish
- Elucidating the Mechanism of Temporal Adaptation to Hydrogen Peroxide‐Induced Oxidative Stress in <i>Corynebacterium glutamicum</i>
- The transcriptome response of astronaut leukocytes to long missions aboard the International Space Station reveals immune modulation
- <i>SHORT AND CROOKED AWN</i>, encoding the epigenetic regulator EMF1, promotes barley awn development
- Transgenerational effects of heat shock on gene regulation and fitness-related traits in natural <i>Drosophila</i> populations
- Serotonin transporter inhibits antitumor immunity through regulating the intratumoral serotonin axis
- Navigating the Cold: Integrative Transcriptome Sequencing Approach Reveals Ionoregulatory and Whole-Body Responses to Cold Acclimation in <i>Drosophila ananassae</i>
- Population genomic analysis unravels the evolutionary processes leading to budding speciation
- Caloric restriction prevents inheritance of polycystic ovary syndrome through oocyte-mediated DNA methylation reprogramming
- SARS-CoV-2 Exploits Host Translation and Immune Evasion Pathways via Viral RNA–Host Protein Interactions
- Phospholipid Scramblase 1 (PLSCR1) Regulates Interferon-Lambda Receptor 1 (IFN-λR1) and IFN-λ Signaling in Influenza A Virus (IAV) Infection
- Sex-specific role of epigenetic modification of a leptin upstream enhancer in adipose tissue
- Multiomics integration unveils photoperiodic plasticity in the molecular rhythms of marine phytoplankton
- ATG9 vesicles are a subtype of intracellular nanovesicle
- High-frequency rTMS mitigates acute sleep deprivation-induced anxiety-like behaviors and working memory impairments associated with hippocampal transcriptional modulation
- Epigenetic training of human bronchial epithelium cells by repeated rhinovirus infections
- Transcriptome-Wide Profiling of Nascent RNA in Neurons with Enriched H3K27ac Signal Elevates eRNA Identification Efficiency
- Nutrient-driven dedifferentiation of enteroendocrine cells promotes adaptive intestinal growth in Drosophila
- Patterns of Local Adaptation in the Northern Leopard Frog ( <i>Rana pipiens</i> ) From a Region Undergoing Rapid Climate and Land‐Use Change
- A hypothesis of mesenchymal stem cell osteogenic differentiation mediated by chelidonic acid through the calcium import: original research and computer simulation
- The gold-ringed octopus (Amphioctopus fangsiao) genome and cerebral single-nucleus transcriptomes provide insights into the evolution of karyotype and neural novelties
- Polyunsaturated lipid senolytics exploit a ferroptotic vulnerability in senescent cells
- IL1A enhances TNF-induced retinal ganglion cell death
- Multifaceted conserved functions of Notch during post-embryonic neurogenesis in the annelid Platynereis
- The impact of rearing environment on <i>C. elegans</i> : phenotypic, transcriptomic and intergenerational responses to 3D enriched habitats
- Human vascularized macrophage-islet organoids to model immune-mediated pancreatic β cell pyroptosis upon viral infection
- Evolution of Sex-Biased Gene Expression During Transitions to Separate Sexes in the <i>Silene</i> Genus
- Anti-progestin therapy targets hallmarks of breast cancer risk
- Fecal microbial load is a major determinant of gut microbiome variation and a confounder for disease associations
- Importance of De Novo Gene Evolution to Emerging Viral Threats: The ORF10 Strain-Restricted Orphan Gene of SARS-CoV-2 Promotes Pathogenesis
- Elucidating human gut microbiota interactions that robustly inhibit diverse Clostridioides difficile strains across different nutrient landscapes
- Largest-Scale Genomic Resource Reconstructing the Genetic Origin, Population Structure, and Biological Adaptations of the Hui People
- Enzyme-converted O kidneys allow ABO-incompatible transplantation without hyperacute rejection in a human decedent model
- CD71 <sup>+</sup> erythroid cell expansion in late‐onset systemic lupus erythematosus
- The nuclear pore complex acts as a hub for pri-miRNA transcription and processing in plants
- β-hydroxybutyrate is a metabolic regulator of proteostasis in the aged and Alzheimer disease brain
- PscOA: a plant scRNA-seq marker gene database for enhanced cellular transcriptome understanding
- Functional characterization of podocyte-expressed THSD7A in experimental membranous nephropathy
- Nr4a1 modulates inflammation and heart regeneration in zebrafish
- A preserved TGFβ cytostatic response through DLD-mediated metabolic modulation undermines anti-TGFβ therapy in gastric cancer
- Genome analysis of dark-adapted variants identifies the phosphatase gene <i>phsP</i> involved in the regulation of photosynthetic and dark-heterotrophic growth in the cyanobacterium <i>Leptolyngbya boryana</i>
- ASPEN: Robust detection of allelic dynamics in single cell RNA-seq
- Respiratory viral infections awaken metastatic breast cancer cells in lungs
- Genome-wide Parallelism Underlies Rapid Freshwater Adaptation Fueled by Standing Genetic Variation in a Wild Fish
- Physiological and genetic basis of superior phosphate uptake and utilization efficiency in the rice landrace Wazuhophek
- Genomic and epigenomic insight into giga-chromosome architecture and adaptive evolution of royal lily (Lilium regale)
- RNA codon expansion via programmable pseudouridine editing and decoding
- Human glial progenitors transplanted into Huntington disease mice normalize neuronal gene expression, dendritic structure, and behavior
- Denoising Single-Cell RNA-Seq Data with a Deep Learning-Embedded Statistical Framework
- Divergent Cardiovascular Adaptations and Gene Regulation in High-Elevation Natives and Recent Colonizers of the Qinghai-Tibetan Plateau
- LXR pathway drives hormonal response intensity in polycystic ovary syndrome
- A biGWAS strategy reveals the genetic architecture of the interaction between wheat and <i>Blumeria graminis</i> f. sp. <i>tritici</i>
- Pan-Genome Analysis Reveals Local Adaptation to Climate Driven by Introgression in Oak Species
- Time‐course transcriptome and chromatin accessibility analyses reveal the dynamic transcriptional regulation shaping spikelet hull size
- Single-cell atlas of endothelial and mural cells across primary and metastatic brain tumors
- Spatiotemporal single-cell roadmap of human skin wound healing
- Integration of single‐cell and bulk <scp>RNA</scp> ‐sequencing data reveals the prognostic potential of epithelial gene markers for prostate cancer
- <i>Arabidopsis</i> natural variation induces complex transcriptomic heterochronies at the floral transition and perturbs the coupling between leaf and flower development by an unexpected genetic control
- A single gene orchestrates androgen variation underlying male mating morphs in ruffs
- Circatidal control of gene expression in the deep-sea hot vent shrimp <i>Rimicaris leurokolos</i>
- Adipocyte-derived ferroptotic signaling mitigates obesity
- From silence to song: Testosterone triggers extensive transcriptional changes in the female canary <scp>HVC</scp>
- Common modes of ERK induction resolve into context-specific signalling via emergent networks and cell-type-specific transcriptional repression
- Population genomics highlights structural variations in local adaptation to saline coastal environments in woolly grape
- Under the Cover of Darkness: A Transcriptomic Exploration of Clubroot During the Night
- Phylogenomic analysis of vocal fold length evolution reveals links between vocal and auditory systems in terrestrial mammals
- Oligodendrocyte transcription factor 2 orchestrates glioblastoma immune evasion by suppressing CXCL10 and CD8+ T cell activation
- Origins and impact of extrachromosomal DNA
- Spatiotemporal regulation of arbuscular mycorrhizal symbiosis at cellular resolution
- Glutathione metabolism-related gene signature predicts prognosis and treatment response in low-grade glioma
- ATF6 activation alters colonic lipid metabolism causing tumour-associated microbial adaptation
- Full spatio-temporal analyses of migration and colonization in evolution—dense 3D mapping of cancer metastases provides new insights
- <i>SNRK3.15</i> Is a Crucial Component of the Sulfur Deprivation Response in <scp> <i>Arabidopsis thaliana</i> </scp>
- Tri-AD: Hippocampal cell-type-specific responses to age, sex and APOE genotype
- VirTrack: A Framework for Inferring Viral Influence on Disease-Associated Transcriptomes — Clinical Type-Specific Epstein–Barr Virus Pathogenesis in Multiple Sclerosis
- Inactivation of Pkd2 in adult mice results in delayed cyst formation and identifies sex as a major modifier of disease severity
- Deciphering the Impact of Temperature on Pleiotropic Consequences of RNA Polymerase Mutations
- The <i>Spirogyra</i> genome: signatures of shared and divergent division and differentiation
- The transcriptional mechanism behind Mimosa pudica leaf folding in response to mechanical disturbance
- <scp>NAXD</scp> Deficiency: Heterogeneous Phenotypes and Positive Response to Niacin Treatment
- Longitudinal clinical proteomics reveals pneumonia type–specific protein biomarkers and autoantibodies
- TM4SF1 as a Prognostic Biomarker and Therapeutic Target in Cervical Cancer
- Drought re-routes soil microbial carbon metabolism towards emission of volatile metabolites in an artificial tropical rainforest
- Newly Identified Transcriptomic Biomarkers and Gene Signature of Pathological Complete Response to Induction Chemoimmunotherapy in Locally Advanced Head and Neck Squamous Cell Carcinoma
- Comprehensive human proteome profiles across a 50-year lifespan reveal aging trajectories and signatures
- Killer-cell immunoglobulin-like receptors define a potent effector program in human γδ T cells
- EPLINα controls integrin recycling from Rab21 endosomes to drive breast cancer cell migration
- Collagen IV assembly is influenced by fluid flow in kidney cell-derived matrices
- Gene Expression and Physiological Analyses Provide New Insights Toward Adventitious Rooting in Yellow Camellia (C. nitidissima)
- Polystyrene nanoplastics modulate neurite length in a size-specific manner
- MetMiner: A user‐friendly pipeline for large‐scale plant metabolomics data analysis
- Phospho-regulation of ASCL1-mediated chromatin opening during cellular reprogramming
- Complete telomere-to-telomere genomes of cowpea reveal insights into centromere evolution in Phaseoleae
- Disruption of hnRNP A2-mediated RNA dynamics by amyloid-β drives MBP increase in Alzheimer’s disease
- Meta-Research: Understudied genes are lost in a leaky pipeline between genome-wide assays and reporting of results
- The telomere-to-telomere gapless genome of grass carp provides insights for genetic improvement
- The transcriptional mechanism behind <i>Mimosa pudica</i> leaf folding in response to mechanical disturbance
- White-Brown switching controls phenotypic plasticity and virulence of Candida auris
- Chemical reprogramming ameliorates cellular hallmarks of aging and extends lifespan
- Cerebrospinal fluid proteome of patients with persistent pain and/or postpartum depression after elective cesarean delivery: An exploratory prospective cohort study
- Population Genomics Provides Insights Into Genomic Features of Inbreeding Depression in <i>Arma Chinensis</i>
- Targeting senescent hepatocytes for treatment of metabolic dysfunction-associated steatotic liver disease and multi-organ dysfunction
- Telomere-to-telomere genome of common bean (<i>Phaseolus vulgaris</i> L., YP4)
- RNA binding as an emerging regulatory dimension in the type I IFN response
- Spontaneous aging-associated inflammation and genome instability in the immune system of turquoise killifish
- Allogeneic CD33-directed CAR-NKT cells for the treatment of bone marrow-resident myeloid malignancies
- A simple method to efficiently generate structural variation in plants
- DNA Methylation in Blood Samples from Malignant Mammary Tumors of Companion Dogs: A Pilot Study
- Temporal transcriptomic changes in the THY-Tau22 mouse model of tauopathy display cell type- and sex-specific differences
- Bnip3lb-driven mitophagy maintains fate of the embryonic hematopoietic stem cell pool
- Global analysis of protein turnover dynamics in single cells
- Population genomics of Vitis pseudoreticulata reveals the genetic basis of fungal resistance in grapevine
- Epigenetic dysregulation of IRF9 drives excessive interferon signaling in COPD
- Genomic and transcriptomic analyses of <i>Heteropoda venatoria</i> reveal the expansion of P450 family for starvation resistance in spiders
- Characterization of a novel zebrafish model of <i>MTMR5</i>-associated Charcot-Marie-Tooth disease type 4B3
- Recruitment, rewiring, and deep conservation in flowering plant gene regulation
- Epithelia mediate inflammation with myeloid cells in Crohn’s disease patients under treatment
- Asian diversity in human immune cells
- Growth of the maternal intestine during reproduction
- The telomere-to-telomere genome of flowering cherry (<i>Prunus campanulata</i>) reveals genomic evolution of the subgenus <i>Cerasus</i>
- A pan-gene catalogue of Asian cultivated rice
- Grapevine pangenome facilitates trait genetics and genomic breeding
- A multiorgan map of metabolic, signaling, and inflammatory pathways that coordinately control fasting glycemia in mice
- The multi-level effect of chlorpyrifos during clownfish metamorphosis
- K6-linked ubiquitylation marks formaldehyde-induced RNA-protein crosslinks for resolution
- <i>ggkegg</i>: analysis and visualization of KEGG data utilizing the grammar of graphics
- Systematic analysis of drug combinations against Gram-positive bacteria
- Tracing the Origins of Human Disease: A Phylogenomic Toolkit for Identifying Evolutionary Trade‐Offs
- 6PPD-quinone exposure and Alzheimer’s disease: insights from integrative network pharmacology, transcriptomics, machine learning, and molecular docking
- Harnessing the glycolysis-TCA cycle axis to boost host defense against neonatal infection
- Rapid Human Skin Barrier Disruption by Sodium Dodecyl Sulfate and Associated Molecular Mechanisms
- Multi-omics characterization of developing forebrain organoids unravels the dynamic molecular events of Rett syndrome pathogenesis
- Allelic variation at a single locus distinguishes spring and winter faba beans
- Transcriptome profiling reveals divergent response strategies in two olive cultivars with contrasting drought tolerance
- IL-17–producing γδ T cells in the tumor microenvironment promote radioresistance in mice
- The Molecular and Functional Landscape of Resistance to FOLFIRI Chemotherapy in Metastatic Colorectal Cancer
- Symbionts with eroded genomes adjust gene expression according to host life-stage and environment
- Recurrent disruption of tumour suppressor genes in cancer by somatic mutations in cleavage and polyadenylation signals
- Multi-scaled transcriptomics of chronically inflamed nasal epithelium reveals immune-epithelial dynamics and tissue remodeling in nasal polyp formation
- 3D genomic features across >50 diverse cell types reveal insights into the genomic architecture of childhood obesity
- The RNA-binding protein SRSF3 controls epicardial formation by regulating splicing and proliferation
- Contrasting epigenetic dynamics in chromosome arms and pericentromeres during ROS1-induced plant immune memory
- Psychodietetics: Food As the Key to Emotional Health
- The Human Developing Cerebral Cortex Is Characterized by an Elevated De Novo Expression of Long Noncoding RNAs in Excitatory Neurons
- Late-acting self-incompatibility in Asimina triloba: implications for the evolution of self-incompatibility in angiosperms
- Carbon dioxide fertilization effect on rice yield is not sustained over multiple generations
- Evolutionary remodeling of non-canonical ORF translation in mammals
- VirTarget: Virus-Informed Pharmacogenomics Framework Identifies Immunotherapies That Mitigate Epstein–Barr Virus–Driven Dysregulation in Multiple Sclerosis
- The innate thermogenic capacity of brown adipose tissue develops independently of sympathetic signaling
- Non-linear microglial, inflammatory and oligodendrocyte dynamics across stages of Alzheimer's disease
- SiCmiR Atlas: Single-Cell miRNA Landscapes Reveals Hub-miRNA and Network Signatures in Human Cancers
- Immunoglobulin M regulates airway hyperresponsiveness independent of T helper 2 allergic inflammation
- MITF regulates autophagy and extracellular vesicle cargo in gastrointestinal stromal tumors
- Stacking of anthocyanin related QTLs in the chromosome 10 and postulation of SmNac-like gene to be involve in anthocyanin biodhynthesis
- The life-saving benefit of dexamethasone in severe COVID-19 is linked to a reversal of monocyte dysregulation
- ANTXR1 blockade enhances cardiac function in preclinical models of heart failure
- <scp>ERSAtool</scp> : A User‐Friendly R/Shiny Comprehensive Transcriptomic Analysis Interface Suitable for Education
- Deciphering brain organoid heterogeneity by identifying key quality determinants
- Effect of complement 3/5 knockout on renal proteomics landscape after ischemia and reperfusion injury in rats
- Telomere to telomere flax (<i>Linum usitatissimum</i> L.) genome assembly unlocks insights beyond fatty acid metabolism pathways
- Laticifer-specific engineering of rubber biosynthesis in Taraxacum kok-saghyz
- Identification of traumatic intracerebral hemorrhage associated metabolites using untargeted metabolomics
- Comprehensive Bioinformatics Method to Explore Immune-Related Genes in the Pathogenesis of Myocardial Infarction
- miR-302 regulates pancreatic progenitor pool and pancreatic size
- Multiomics alterations associated with tolerance and response to simulated progressive hemorrhage in healthy adult humans
- PDGFRα+ fibroblast ablation exacerbates pathologic features in a model of house dust mite-induced allergenic asthma
Related