Showing papers by "Institute for Systems Biology published in 2018"
Institute for Systems Biology1, BC Cancer Agency2, University of California, San Francisco3, University of North Carolina at Chapel Hill4, Columbia University5, Discovery Institute6, Massachusetts Institute of Technology7, Arizona State University8, Sage Bionetworks9, Harvard University10, Johns Hopkins University11, Stanford University12, University of Calgary13, Université libre de Bruxelles14, University of Texas MD Anderson Cancer Center15, Medical College of Wisconsin16, Qatar Airways17, Cold Spring Harbor Laboratory18, University of São Paulo19, Henry Ford Hospital20, University of Alabama at Birmingham21, Van Andel Institute22, Stony Brook University23
TL;DR: An extensive immunogenomic analysis of more than 10,000 tumors comprising 33 diverse cancer types by utilizing data compiled by TCGA identifies six immune subtypes that encompass multiple cancer types and are hypothesized to define immune response patterns impacting prognosis.
3,246 citations
Nationwide Children's Hospital1, University of North Carolina at Chapel Hill2, Henry Ford Health System3, University of Texas MD Anderson Cancer Center4, Broad Institute5, Walter Reed National Military Medical Center6, Buck Institute for Research on Aging7, New York University8, University of Pittsburgh9, Sage Bionetworks10, University of California, San Francisco11, Institute for Systems Biology12
TL;DR: These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale.
1,928 citations
Memorial Sloan Kettering Cancer Center1, Swiss Institute of Bioinformatics2, Harvard University3, Princeton University4, University of Texas at Dallas5, Washington University in St. Louis6, Institute for Systems Biology7, Bilkent University8, Van Andel Institute9, University of Pennsylvania10, University of Texas MD Anderson Cancer Center11, Mayo Clinic12, Columbia University Medical Center13, Fred Hutchinson Cancer Research Center14, University of California, San Francisco15, University of Michigan16, Peter MacCallum Cancer Centre17, Baylor College of Medicine18
TL;DR: This work charted the detailed landscape of pathway alterations in 33 cancer types, stratified into 64 subtypes, and identified patterns of co-occurrence and mutual exclusivity.
1,841 citations
TL;DR: Molecular similarities among histologically or anatomically related cancer types provide a basis for focused pan-cancer analyses, such as pan-gastrointestinal, Pan-gynecological, pan-kidney, and pan-squamous cancers, and those related by stemness features, which may inform strategies for future therapeutic development.
1,535 citations
Institute for Systems Biology1, University of Texas MD Anderson Cancer Center2, Mayo Clinic3, Massachusetts Institute of Technology4, Van Andel Institute5, University of Pennsylvania6, Baylor College of Medicine7, Texas A&M University8, University of Texas Health Science Center at Houston9, Washington University in St. Louis10, Buck Institute for Research on Aging11, University of California, San Francisco12, University of Texas at Austin13, University of Washington14
TL;DR: These frequent DDR gene alterations in many human cancers have functional consequences that may determine cancer progression and guide therapy and a new machine-learning-based classifier developed from gene expression data allowed to identify alterations that phenocopy deleterious TP53 mutations.
706 citations
TL;DR: Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment.
655 citations
Washington University in St. Louis1, Baylor College of Medicine2, Xi'an Jiaotong University3, Ontario Institute for Cancer Research4, Institute for Systems Biology5, Broad Institute6, University of Texas MD Anderson Cancer Center7, Mayo Clinic8, Kuwait University9, University of Toronto10, Princeton University11, Wake Forest University12
TL;DR: The largest investigation of predisposition variants in cancer to date finds 853 pathogenic or likely pathogenic variants in 8% of 10,389 cases from 33 cancer types, informing future guidelines of variant classification and germline genetic testing in cancer.
543 citations
TL;DR: This study constructs multiscale networks of the late-onset AD-associated virome, and elucidates networks linking molecular, clinical, and neuropathological features with viral activity and indicates viral activity constituting a general feature of AD.
495 citations
TL;DR: This work elucidates the architecture and assembly pathway across three classes of mSWI/SNF complexes-canonical BRG1/BRM-associated factor (BAF), polybromo-associated BAF (PBAF, and newly defined ncBAF complexes) and defines the requirement of each subunit for complex formation and stability.
418 citations
Memorial Sloan Kettering Cancer Center1, University of North Carolina at Chapel Hill2, Massachusetts Institute of Technology3, Wellcome Trust Sanger Institute4, Johns Hopkins University5, BC Cancer Agency6, University of Texas MD Anderson Cancer Center7, University of Tokyo8, University of California, Santa Cruz9, Institute for Systems Biology10, University of Texas at Dallas11, Brigham and Women's Hospital12, University of Bologna13, University of Pittsburgh14, University of Chicago15, University of Cambridge16, New York University17, University of Western Australia18, The Research Institute at Nationwide Children's Hospital19, National Institutes of Health20
TL;DR: A comprehensive integrated genomic study of 74 MPMs provided a deeper understanding of histology-independent determinants of aggressive behavior, defined a novel genomic subtype with TP53 and SETDB1 mutations and extensive loss of heterozygosity, and discovered strong expression of the immune-checkpoint gene VISTA in epithelioid MPM.
Abstract: Malignant pleural mesothelioma (MPM) is a highly lethal cancer of the lining of the chest cavity. To expand our understanding of MPM, we conducted a comprehensive integrated genomic study, including the most detailed analysis of BAP1 alterations to date. We identified histology-independent molecular prognostic subsets, and defined a novel genomic subtype with TP53 and SETDB1 mutations and extensive loss of heterozygosity. We also report strong expression of the immune checkpoint gene VISTA in epithelioid MPM, strikingly higher than in other solid cancers, with implications for the immune response to MPM and for its immunotherapy. Our findings highlight new avenues for further investigation of MPM biology and novel therapeutic options.
388 citations
California Institute for Quantitative Biosciences1, Rockefeller University2, Institute for Systems Biology3, Stowers Institute for Medical Research4, Indiana University5, New York University6, Howard Hughes Medical Institute7, Center for Infectious Disease Research and Policy8, Baylor College of Medicine9, Boston University10
TL;DR: The structure of the entire 552-protein nuclear pore complex of the yeast Saccharomyces cerevisiae is determined at sub-nanometre precision by satisfying a wide range of data relating to the molecular arrangement of its constituents.
Abstract: Nuclear pore complexes play central roles as gatekeepers of RNA and protein transport between the cytoplasm and nucleoplasm. However, their large size and dynamic nature have impeded a full structural and functional elucidation. Here we determined the structure of the entire 552-protein nuclear pore complex of the yeast Saccharomyces cerevisiae at sub-nanometre precision by satisfying a wide range of data relating to the molecular arrangement of its constituents. The nuclear pore complex incorporates sturdy diagonal columns and connector cables attached to these columns, imbuing the structure with strength and flexibility. These cables also tie together all other elements of the nuclear pore complex, including membrane-interacting regions, outer rings and RNA-processing platforms. Inwardly directed anchors create a high density of transport factor-docking Phe-Gly repeats in the central channel, organized into distinct functional units. This integrative structure enables us to rationalize the architecture, transport mechanism and evolutionary origins of the nuclear pore complex.
Massachusetts Institute of Technology1, Harvard University2, Van Andel Institute3, Vanderbilt University Medical Center4, Memorial Sloan Kettering Cancer Center5, Stanford University6, University of Calgary7, BC Cancer Agency8, University of Texas MD Anderson Cancer Center9, Case Western Reserve University10, Mayo Clinic11, Duke University12, George Washington University13, University of Alabama at Birmingham14, Institute for Systems Biology15
TL;DR: A group of tumors in the colon and rectum lacking hypermutation and aneuploidy termed genome stable and enriched in DNA hypermethylation and mutations in KRAS, SOX9, and PCBP1 is identified.
TL;DR: Gene fusions represent an important class of somatic alterations in cancer, and integration of gene expression, copy number, and fusion annotation data revealed that fusions involving oncogenes tend to exhibit increased expression, whereas fusion involving tumor suppressors have the opposite effect.
Van Andel Institute1, Tufts University2, University of North Carolina at Chapel Hill3, University of Texas MD Anderson Cancer Center4, BC Cancer Agency5, Memorial Sloan Kettering Cancer Center6, Institute for Systems Biology7, University of California, Santa Cruz8, University of Pennsylvania9, Children's Hospital of Philadelphia10, University of Michigan11, Baylor College of Medicine12, University of Wisconsin-Madison13, University of Hamburg14, University of Zagreb15, The Research Institute at Nationwide Children's Hospital16, Massachusetts Institute of Technology17, National Institutes of Health18, University of Southern California19
TL;DR: High-dimensional analyses identified distinct molecular patterns that characterized the major recognized histologic subtypes of TGCT: seminoma, embryonal carcinoma, yolk sac tumor, and teratoma, and a subset of pure seminomas defined by KIT mutations, increased immune infiltration, globally demethylated DNA, and decreased KRAS copy number.
Washington University in St. Louis1, Discovery Institute2, Institute for Systems Biology3, Université libre de Bruxelles4, Genome Institute of Singapore5, Johns Hopkins University6, University of Cambridge7, Baylor College of Medicine8, Broad Institute9, Harvard University10, University of Texas MD Anderson Cancer Center11, University of California, Santa Cruz12, University of North Carolina at Chapel Hill13, National Institutes of Health14
TL;DR: Results from the TCGA PanCancer Atlas project will anchor future characterization of rare and common tumor types, primary and relapsed tumors, and cancers across ancestry groups and will guide the deployment of clinical genomic sequencing.
TL;DR: expression analysis revealed MYC-associated pathways in tumor subtypes, such as immune response and growth factor signaling, and chromatin, translation, and DNA replication/repair were conserved pan-cancer, suggesting that MYC is a distinct oncogenic driver.
Abstract: Although the MYC oncogene has been implicated in cancer, a systematic assessment of alterations of MYC, related transcription factors, and co-regulatory proteins, forming the proximal MYC network (PMN), across human cancers is lacking. Using computational approaches, we define genomic and proteomic features associated with MYC and the PMN across the 33 cancers of The Cancer Genome Atlas. Pan-cancer, 28% of all samples had at least one of the MYC paralogs amplified. In contrast, the MYC antagonists MGA and MNT were the most frequently mutated or deleted members, proposing a role as tumor suppressors. MYC alterations were mutually exclusive with PIK3CA, PTEN, APC, or BRAF alterations, suggesting that MYC is a distinct oncogenic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such as immune response and growth factor signaling; chromatin, translation, and DNA replication/repair were conserved pan-cancer. This analysis reveals insights into MYC biology and is a reference for biomarkers and therapeutics for cancers with alterations of MYC or the PMN.
TL;DR: It is hoped that this review could provide a comprehensive overview of the studies on the interactions between the gut microbiota and GI cancers, which are likely to yield translational opportunities to reduce cancer morbidity and mortality by improving prevention, diagnosis, and treatment.
TL;DR: A molecular link between thymoma and the autoimmune disease myasthenia gravis is identified, characterized by tumoral overexpression of muscle autoantigens, and increased aneuploidy.
TL;DR: The isolation of catch bonds as a parameter mediating the coupling of TCR binding and signaling has important implications for TCR and antigen engineering for immunotherapy.
TL;DR: It is found that neoantigens induced by SCMs are likely several folds more immunogenic compared to missense mutations, exemplified by the recurrent GATA3 SCM, suggesting candidates for immune blockade therapy.
TL;DR: ‘metabolically rationalized standard’ assay conditions were devised, in which glutaminase-1 inhibition reduced glutamine metabolism differently in both cell lines assayed, and decreased the proliferation of one of them, which led to an improvement in reproducibility.
Abstract: Optimization of experimental conditions is critical in ensuring robust experimental reproducibility. Through detailed metabolomic analysis we found that cell culture conditions significantly impacted on glutaminase (GLS1) sensitivity resulting in variable sensitivity and irreproducibility in data. Baseline metabolite profiling highlighted that untreated cells underwent significant changes in metabolic status. Both the extracellular levels of glutamine and lactate and the intracellular levels of multiple metabolites changed drastically during the assay. We show that these changes compromise the robustness of the assay and make it difficult to reproduce. We discuss the implications of the cells' metabolic environment when studying the effects of perturbations to cell function by any type of inhibitor. We then devised 'metabolically rationalized standard' assay conditions, in which glutaminase-1 inhibition reduced glutamine metabolism differently in both cell lines assayed, and decreased the proliferation of one of them. The adoption of optimized conditions such as the ones described here should lead to an improvement in reproducibility and help eliminate false negatives as well as false positives in these assays.
University Medical Center Groningen1, Karolinska Institutet2, University of Paris3, Utrecht University4, National Health Service5, University of Southern California6, Maastricht University7, University of Crete8, University of Valencia9, University of Bologna10, Oslo University Hospital11, University of Oslo12, University of Helsinki13, McGill University14, University of Cambridge15, Institute for Systems Biology16, Boston Children's Hospital17, University of Basel18, Swiss Tropical and Public Health Institute19, University of Arizona20, Pompeu Fabra University21, University of Tampere22, French Institute of Health and Medical Research23, Radboud University Nijmegen24, National Institutes of Health25, Charité26, University of Montpellier27, University of Eastern Finland28, Université du Québec à Chicoutimi29, University of the Basque Country30, King's College London31, Stockholm County Council32
TL;DR: In this paper, a large-scale epigenome-wide association study (EWAS) within the Mechanisms of the Development of ALLergy (MeDALL) project was conducted to assess methylation profiles associated with childhood asthma.
Carlos III Health Institute1, Institute of Tropical Medicine Antwerp2, Food and Agriculture Organization3, Swiss Tropical and Public Health Institute4, University of Basel5, Institut de recherche pour le développement6, Instituto de Medicina Molecular7, World Health Organization8, University of Glasgow9, Makerere University10, University of Liverpool11, Foundation for Innovative New Diagnostics12, Institute for Systems Biology13, Pasteur Institute14, University of Dschang15
TL;DR: It is argued that a better understanding of the contribution of human and putative animal reservoirs to gambiense-HAT epidemiology is mandatory to inform elimination strategies.
University of Michigan1, Pacific Northwest Diabetes Research Institute2, University of California, San Francisco3, University of California, San Diego4, University of Massachusetts Medical School5, Translational Genomics Research Institute6, Beth Israel Deaconess Medical Center7, Harvard University8, Institute for Systems Biology9, Utrecht University10, Leiden University Medical Center11
TL;DR: Results obtained by a consortium of nine labs that independently sequenced reference, 'ground truth' samples of synthetic small RNAs and human plasma-derived RNA found that microRNA relative quantification between samples using small RNA-seq was accurate and reproducible across laboratories and methods.
Abstract: RNA-seq is increasingly used for quantitative profiling of small RNAs (for example, microRNAs, piRNAs and snoRNAs) in diverse sample types, including isolated cells, tissues and cell-free biofluids. The accuracy and reproducibility of the currently used small RNA-seq library preparation methods have not been systematically tested. Here we report results obtained by a consortium of nine labs that independently sequenced reference, 'ground truth' samples of synthetic small RNAs and human plasma-derived RNA. We assessed three commercially available library preparation methods that use adapters of defined sequence and six methods using adapters with degenerate bases. Both protocol- and sequence-specific biases were identified, including biases that reduced the ability of small RNA-seq to accurately measure adenosine-to-inosine editing in microRNAs. We found that these biases were mitigated by library preparation methods that incorporate adapters with degenerate bases. MicroRNA relative quantification between samples using small RNA-seq was accurate and reproducible across laboratories and methods.
University Medical Center Groningen1, Karolinska Institutet2, University of Paris3, Utrecht University4, National Health Service5, University of Southern California6, Maastricht University7, University of Crete8, University of Valencia9, University of Bologna10, Oslo University Hospital11, University of Oslo12, University of Helsinki13, McGill University14, Institute for Systems Biology15, University of Cambridge16, Boston Children's Hospital17, Swiss Tropical and Public Health Institute18, University of Basel19, University of Arizona20, Pompeu Fabra University21, University of Tampere22, French Institute of Health and Medical Research23, Radboud University Nijmegen24, National Institutes of Health25, University of Montpellier26, Charité27, University of Eastern Finland28, Université du Québec à Chicoutimi29, University of the Basque Country30, King's College London31, Stockholm County Council32
TL;DR: In this paper, a large-scale epigenome-wide association study (EWAS) within the Mechanisms of the Development of ALLergy (MeDALL) project was conducted to assess methylation profiles associated with childhood asthma.
Abstract: Summary Background DNA methylation profiles associated with childhood asthma might provide novel insights into disease pathogenesis. We did an epigenome-wide association study to assess methylation profiles associated with childhood asthma. Methods We did a large-scale epigenome-wide association study (EWAS) within the Mechanisms of the Development of ALLergy (MeDALL) project. We examined epigenome-wide methylation using Illumina Infinium Human Methylation450 BeadChips (450K) in whole blood in 207 children with asthma and 610 controls at age 4–5 years, and 185 children with asthma and 546 controls at age 8 years using a cross-sectional case-control design. After identification of differentially methylated CpG sites in the discovery analysis, we did a validation study in children (4–16 years; 247 cases and 2949 controls) from six additional European cohorts and meta-analysed the results. We next investigated whether replicated CpG sites in cord blood predict later asthma in 1316 children. We subsequently investigated cell-type-specific methylation of the identified CpG sites in eosinophils and respiratory epithelial cells and their related gene-expression signatures. We studied cell-type specificity of the asthma association of the replicated CpG sites in 455 respiratory epithelial cell samples, collected by nasal brushing of 16-year-old children as well as in DNA isolated from blood eosinophils (16 with asthma, eight controls [age 2–56 years]) and compared this with whole-blood DNA samples of 74 individuals with asthma and 93 controls (age 1–79 years). Whole-blood transcriptional profiles associated with replicated CpG sites were annotated using RNA-seq data of subsets of peripheral blood mononuclear cells sorted by fluorescence-activated cell sorting. Findings 27 methylated CpG sites were identified in the discovery analysis. 14 of these CpG sites were replicated and passed genome-wide significance (p −7 ) after meta-analysis. Consistently lower methylation levels were observed at all associated loci across childhood from age 4 to 16 years in participants with asthma, but not in cord blood at birth. All 14 CpG sites were significantly associated with asthma in the second replication study using whole-blood DNA, and were strongly associated with asthma in purified eosinophils. Whole-blood transcriptional signatures associated with these CpG sites indicated increased activation of eosinophils, effector and memory CD8 T cells and natural killer cells, and reduced number of naive T cells. Five of the 14 CpG sites were associated with asthma in respiratory epithelial cells, indicating cross-tissue epigenetic effects. Interpretation Reduced whole-blood DNA methylation at 14 CpG sites acquired after birth was strongly associated with childhood asthma. These CpG sites and their associated transcriptional profiles indicate activation of eosinophils and cytotoxic T cells in childhood asthma. Our findings merit further investigations of the role of epigenetics in a clinical context. Funding EU and the Seventh Framework Programme (the MeDALL project).
TL;DR: This work used cryo-electron microscopy, chemical crosslinking-mass spectrometry and biochemical reconstitution to determine the complete molecular architecture of TFIID and define the conformational landscape of T FIID in the process of TATA-box binding protein (TBP) loading onto promoter DNA.
Abstract: The general transcription factor IID (TFIID) is a critical component of the eukaryotic transcription preinitiation complex (PIC) and is responsible for recognizing the core promoter DNA and initiating PIC assembly. We used cryo-electron microscopy (cryo-EM), chemical crosslinking-mass spectrometry (CX-MS) and biochemical reconstitution to determine the complete molecular architecture of TFIID and define the conformational landscape of TFIID in the process of TATA-box binding protein (TBP) loading onto promoter DNA. Our structural analysis revealed five structural states of TFIID in the presence of TFIIA and promoter DNA, showing that the initial binding of TFIID to the downstream promoter positions the upstream DNA and facilitates scanning of TBP for a TATA-box and the subsequent engagement of the promoter. Our findings provide a mechanistic model for the specific loading of TBP by TFIID onto the promoter.
ETH Zurich1, University of Zurich2, European Bioinformatics Institute3, Université de Montréal4, University of Tübingen5, Utrecht University6, Ludwig Institute for Cancer Research7, La Jolla Institute for Allergy and Immunology8, Leiden University Medical Center9, Max Planck Society10, University of Michigan11, Technical University of Denmark12, Institute for Systems Biology13, Karolinska Institutet14, Monash University, Clayton campus15, Boston University16, University of Oxford17, Federal University of Rio Grande do Norte18, Oslo University Hospital19, Technion – Israel Institute of Technology20
TL;DR: The SysteMHC Atlas disseminates quality controlled immunopeptidomic information to the public domain and serves as a community resource toward the generation of a high-quality comprehensive map of the human immunopePTidome and the support of consistent measurement of immunopeethidomic sample cohorts.
Abstract: Mass spectrometry (MS)-based immunopeptidomics investigates the repertoire of peptides presented at the cell surface by major histocompatibility complex (MHC) molecules. The broad clinical relevance of MHC-associated peptides, e.g. in precision medicine, provides a strong rationale for the large-scale generation of immunopeptidomic datasets and recent developments in MS-based peptide analysis technologies now support the generation of the required data. Importantly, the availability of diverse immunopeptidomic datasets has resulted in an increasing need to standardize, store and exchange this type of data to enable better collaborations among researchers, to advance the field more efficiently and to establish quality measures required for the meaningful comparison of datasets. Here we present the SysteMHC Atlas (https://systemhcatlas.org), a public database that aims at collecting, organizing, sharing, visualizing and exploring immunopeptidomic data generated by MS. The Atlas includes raw mass spectrometer output files collected from several laboratories around the globe, a catalog of context-specific datasets of MHC class I and class II peptides, standardized MHC allele-specific peptide spectral libraries consisting of consensus spectra calculated from repeat measurements of the same peptide sequence, and links to other proteomics and immunology databases. The SysteMHC Atlas project was created and will be further expanded using a uniform and open computational pipeline that controls the quality of peptide identifications and peptide annotations. Thus, the SysteMHC Atlas disseminates quality controlled immunopeptidomic information to the public domain and serves as a community resource toward the generation of a high-quality comprehensive map of the human immunopeptidome and the support of consistent measurement of immunopeptidomic sample cohorts.
TL;DR: Comparative transcriptome analyses in Alzheimer's disease (AD) and other neurodegenerative proteinopathies can uncover both shared and distinct disease pathways.
Abstract: Introduction Comparative transcriptome analyses in Alzheimer's disease (AD) and other neurodegenerative proteinopathies can uncover both shared and distinct disease pathways. Methods We analyzed 940 brain transcriptomes including patients with AD, progressive supranuclear palsy (PSP; a primary tauopathy), and control subjects. Results We identified transcriptional coexpression networks implicated in myelination, which were lower in PSP temporal cortex (TCX) compared with AD. Some of these associations were retained even after adjustments for brain cell population changes. These TCX myelination network structures were preserved in cerebellum but they were not differentially expressed in cerebellum between AD and PSP. Myelination networks were downregulated in both AD and PSP, when compared with control TCX samples. Discussion Downregulation of myelination networks may underlie both PSP and AD pathophysiology, but may be more pronounced in PSP. These data also highlight conservation of transcriptional networks across brain regions and the influence of cell type changes on these networks.
TL;DR: It is found that kidney markers are strongly associated with TMAO and CVD-related proteins that are positively correlated with TmaO are identified, and it is shown that metabolites derived by the gut microbiota are strongly correlation with T MAO and that the magnitude of this correlation varies with kidney function.
TL;DR: In this paper, a cross-sectional, observational study was conducted to identify gene profiles associated with adult-onset severe asthma, which is characterized by inflammatory pathways involving eosinophils, mast cells, and group 3 innate lymphoid cells.
Abstract: Background Adult-onset severe asthma is characterized by highly symptomatic disease despite high-intensity asthma treatments. Understanding of the underlying pathways of this heterogeneous disease is needed for the development of targeted treatments. Gene set variation analysis is a statistical technique used to identify gene profiles in heterogeneous samples. Objective We sought to identify gene profiles associated with adult-onset severe asthma. Methods This was a cross-sectional, observational study in which adult patients with adult-onset of asthma (defined as starting at age ≥18 years) as compared with childhood-onset severe asthma ( Results Significant differentially enriched gene signatures in patients with adult-onset as compared with childhood-onset severe asthma were identified in nasal brushings (5 signatures), sputum (3 signatures), and endobronchial brushings (6 signatures). Signatures associated with eosinophilic airway inflammation, mast cells, and group 3 innate lymphoid cells were more enriched in adult-onset severe asthma, whereas signatures associated with induced lung injury were less enriched in adult-onset severe asthma. Conclusions Adult-onset severe asthma is characterized by inflammatory pathways involving eosinophils, mast cells, and group 3 innate lymphoid cells. These pathways could represent useful targets for the treatment of adult-onset severe asthma.