Three-dimensional CRISPR screening reveals epigenetic interaction with anti-angiogenic therapy View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2021-07-15

AUTHORS

Michael Y. He, Michael M. Halford, Ruofei Liu, James P. Roy, Zoe L. Grant, Leigh Coultas, Niko Thio, Omer Gilan, Yih-Chih Chan, Mark A. Dawson, Marc G. Achen, Steven A. Stacker

ABSTRACT

Angiogenesis underlies development, physiology and pathogenesis of cancer, eye and cardiovascular diseases. Inhibiting aberrant angiogenesis using anti-angiogenic therapy (AAT) has been successful in the clinical treatment of cancer and eye diseases. However, resistance to AAT inevitably occurs and its molecular basis remains poorly understood. Here, we uncover molecular modifiers of the blood endothelial cell (EC) response to a widely used AAT bevacizumab by performing a pooled genetic screen using three-dimensional microcarrier-based cell culture and CRISPR–Cas9. Functional inhibition of the epigenetic reader BET family of proteins BRD2/3/4 shows unexpected mitigating effects on EC survival and/or proliferation upon VEGFA blockade. Moreover, transcriptomic and pathway analyses reveal an interaction between epigenetic regulation and anti-angiogenesis, which may affect chromosomal structure and activity in ECs via the cell cycle regulator CDC25B phosphatase. Collectively, our findings provide insight into epigenetic regulation of the EC response to VEGFA blockade and may facilitate development of quality biomarkers and strategies for overcoming resistance to AAT. More... »

PAGES

878

References to SciGraph publications

  • 2018-07-09. Phenotype molding of stromal cells in the lung tumor microenvironment in NATURE MEDICINE
  • 2016-08-11. Transcript-level expression analysis of RNA-seq experiments with HISAT, StringTie and Ballgown in NATURE PROTOCOLS
  • 2010-11-10. Suppression of inflammation by a synthetic histone mimic in NATURE
  • 2015-09-14. BET inhibitor resistance emerges from leukaemia stem cells in NATURE
  • 2017-04-04. Epigenetic approach for angiostatic therapy: promising combinations for cancer treatment in ANGIOGENESIS
  • 2014-12-05. MAGeCK enables robust identification of essential genes from genome-scale CRISPR/Cas9 knockout screens in GENOME BIOLOGY
  • 2016-08-30. Atezolizumab in combination with bevacizumab enhances antigen-specific T-cell migration in metastatic renal cell carcinoma in NATURE COMMUNICATIONS
  • 2010-09-24. Selective inhibition of BET bromodomains in NATURE
  • 2016-01-06. Response and resistance to BET bromodomain inhibitors in triple-negative breast cancer in NATURE
  • 2016-01-18. Ten years of anti-vascular endothelial growth factor therapy in NATURE REVIEWS DRUG DISCOVERY
  • 2014-12-05. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2 in GENOME BIOLOGY
  • 2017-05-24. Vascular heterogeneity and specialization in development and disease in NATURE REVIEWS MOLECULAR CELL BIOLOGY
  • 2017-07-14. Microenvironmental regulation of tumour angiogenesis in NATURE REVIEWS CANCER
  • 2015-04-09. High-throughput functional genomics using CRISPR–Cas9 in NATURE REVIEWS GENETICS
  • 2016-02-15. Tumor angiogenesis—characteristics of tumor endothelial cells in INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY
  • 2017-09-28. Transcriptional regulation of endothelial cell behavior during sprouting angiogenesis in NATURE COMMUNICATIONS
  • 2016-06-13. The BET inhibitor JQ1 selectively impairs tumour response to hypoxia and downregulates CA9 and angiogenesis in triple negative breast cancer in ONCOGENE
  • 2017-08-29. VEGF amplifies transcription through ETS1 acetylation to enable angiogenesis in NATURE COMMUNICATIONS
  • 2017-04-03. Mutual regulation of tumour vessel normalization and immunostimulatory reprogramming in NATURE
  • 2017-03-23. Genome-scale CRISPR-Cas9 knockout and transcriptional activation screening in NATURE PROTOCOLS
  • 2017-11-22. Epigenetic targeting of bromodomain protein BRD4 counteracts cancer cachexia and prolongs survival in NATURE COMMUNICATIONS
  • 2014-03-02. CRISPR-Cas systems for editing, regulating and targeting genomes in NATURE BIOTECHNOLOGY
  • 2014-02-03. voom: precision weights unlock linear model analysis tools for RNA-seq read counts in GENOME BIOLOGY
  • 2011-10-02. Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia in NATURE
  • 2016-04-05. BET Bromodomain Suppression Inhibits VEGF-induced Angiogenesis and Vascular Permeability by Blocking VEGFR2-mediated Activation of PAK1 and eNOS in SCIENTIFIC REPORTS
  • 2016-01-18. Optimized sgRNA design to maximize activity and minimize off-target effects of CRISPR-Cas9 in NATURE BIOTECHNOLOGY
  • 2007-06. Molecular regulation of angiogenesis and lymphangiogenesis in NATURE REVIEWS MOLECULAR CELL BIOLOGY
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s42003-021-02397-3

    DOI

    http://dx.doi.org/10.1038/s42003-021-02397-3

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1139694358

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/34267311


    Indexing Status Check whether this publication has been indexed by Scopus and Web Of Science using the SN Indexing Status Tool
    Incoming Citations Browse incoming citations for this publication using opencitations.net

    JSON-LD is the canonical representation for SciGraph data.

    TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT

    [
      {
        "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
        "about": [
          {
            "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/06", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Biological Sciences", 
            "type": "DefinedTerm"
          }, 
          {
            "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/0601", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Biochemistry and Cell Biology", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Angiogenesis Inhibitors", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Bevacizumab", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Blood", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Clustered Regularly Interspaced Short Palindromic Repeats", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Endothelial Cells", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Epigenesis, Genetic", 
            "type": "DefinedTerm"
          }
        ], 
        "author": [
          {
            "affiliation": {
              "alternateName": "Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada", 
              "id": "http://www.grid.ac/institutes/grid.415224.4", 
              "name": [
                "Tumour Angiogenesis and Microenvironment Program, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia", 
                "Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC, Australia", 
                "Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada"
              ], 
              "type": "Organization"
            }, 
            "familyName": "He", 
            "givenName": "Michael Y.", 
            "id": "sg:person.010730706253.43", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.010730706253.43"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Tumour Angiogenesis and Microenvironment Program, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia", 
              "id": "http://www.grid.ac/institutes/grid.1055.1", 
              "name": [
                "Tumour Angiogenesis and Microenvironment Program, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Halford", 
            "givenName": "Michael M.", 
            "id": "sg:person.01110546207.52", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01110546207.52"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC, Australia", 
              "id": "http://www.grid.ac/institutes/grid.1008.9", 
              "name": [
                "Tumour Angiogenesis and Microenvironment Program, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia", 
                "Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC, Australia"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Liu", 
            "givenName": "Ruofei", 
            "id": "sg:person.0765352520.03", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0765352520.03"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC, Australia", 
              "id": "http://www.grid.ac/institutes/grid.1008.9", 
              "name": [
                "Tumour Angiogenesis and Microenvironment Program, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia", 
                "Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC, Australia"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Roy", 
            "givenName": "James P.", 
            "id": "sg:person.016025604012.02", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.016025604012.02"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Gladstone Institutes, San Francisco, CA, USA", 
              "id": "http://www.grid.ac/institutes/grid.249878.8", 
              "name": [
                "Epigenetics and Development Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia", 
                "Department of Medical Biology, The University of Melbourne, Parkville, VIC, Australia", 
                "Gladstone Institutes, San Francisco, CA, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Grant", 
            "givenName": "Zoe L.", 
            "id": "sg:person.013077405605.23", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.013077405605.23"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Medical Biology, The University of Melbourne, Parkville, VIC, Australia", 
              "id": "http://www.grid.ac/institutes/grid.1008.9", 
              "name": [
                "Epigenetics and Development Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia", 
                "Department of Medical Biology, The University of Melbourne, Parkville, VIC, Australia"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Coultas", 
            "givenName": "Leigh", 
            "id": "sg:person.01125006176.31", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01125006176.31"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Bioinformatics Core, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia", 
              "id": "http://www.grid.ac/institutes/grid.1055.1", 
              "name": [
                "Bioinformatics Core, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Thio", 
            "givenName": "Niko", 
            "id": "sg:person.012152756657.54", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.012152756657.54"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Australian Centre for Blood Diseases, Monash University, Melbourne, VIC, Australia", 
              "id": "http://www.grid.ac/institutes/grid.1002.3", 
              "name": [
                "Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC, Australia", 
                "Translational Haematology Program, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia", 
                "Australian Centre for Blood Diseases, Monash University, Melbourne, VIC, Australia"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Gilan", 
            "givenName": "Omer", 
            "id": "sg:person.0631434345.27", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0631434345.27"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Translational Haematology Program, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia", 
              "id": "http://www.grid.ac/institutes/grid.1055.1", 
              "name": [
                "Translational Haematology Program, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Chan", 
            "givenName": "Yih-Chih", 
            "id": "sg:person.014226777041.19", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.014226777041.19"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Haematology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia", 
              "id": "http://www.grid.ac/institutes/grid.1055.1", 
              "name": [
                "Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC, Australia", 
                "Translational Haematology Program, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia", 
                "Centre for Cancer Research, The University of Melbourne, Parkville, VIC, Australia", 
                "Department of Haematology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Dawson", 
            "givenName": "Mark A.", 
            "id": "sg:person.013455005252.42", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.013455005252.42"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "St Vincent\u2019s Institute of Medical Research, Melbourne, VIC, Australia", 
              "id": "http://www.grid.ac/institutes/grid.1073.5", 
              "name": [
                "Tumour Angiogenesis and Microenvironment Program, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia", 
                "Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC, Australia", 
                "Department of Surgery, Royal Melbourne Hospital, The University of Melbourne, Parkville, VIC, Australia", 
                "St Vincent\u2019s Institute of Medical Research, Melbourne, VIC, Australia"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Achen", 
            "givenName": "Marc G.", 
            "id": "sg:person.01270035270.04", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01270035270.04"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Surgery, Royal Melbourne Hospital, The University of Melbourne, Parkville, VIC, Australia", 
              "id": "http://www.grid.ac/institutes/grid.1008.9", 
              "name": [
                "Tumour Angiogenesis and Microenvironment Program, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia", 
                "Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC, Australia", 
                "Department of Surgery, Royal Melbourne Hospital, The University of Melbourne, Parkville, VIC, Australia"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Stacker", 
            "givenName": "Steven A.", 
            "id": "sg:person.01221722070.50", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01221722070.50"
            ], 
            "type": "Person"
          }
        ], 
        "citation": [
          {
            "id": "sg:pub.10.1186/gb-2014-15-2-r29", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1045312009", 
              "https://doi.org/10.1186/gb-2014-15-2-r29"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/ncomms12624", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1050269937", 
              "https://doi.org/10.1038/ncomms12624"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nbt.2842", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1038520013", 
              "https://doi.org/10.1038/nbt.2842"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nprot.2017.016", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1084129553", 
              "https://doi.org/10.1038/nprot.2017.016"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nrm.2017.36", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1085575671", 
              "https://doi.org/10.1038/nrm.2017.36"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nrg3899", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1013619504", 
              "https://doi.org/10.1038/nrg3899"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nrd.2015.17", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1052866965", 
              "https://doi.org/10.1038/nrd.2015.17"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/s41467-017-00405-x", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1091331666", 
              "https://doi.org/10.1038/s41467-017-00405-x"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nature16508", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1024399927", 
              "https://doi.org/10.1038/nature16508"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nrc.2017.51", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1090661850", 
              "https://doi.org/10.1038/nrc.2017.51"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s10456-017-9551-z", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1084513520", 
              "https://doi.org/10.1007/s10456-017-9551-z"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/s41467-017-01645-7", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1092730297", 
              "https://doi.org/10.1038/s41467-017-01645-7"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nature10509", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1026728956", 
              "https://doi.org/10.1038/nature10509"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nbt.3437", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1014083513", 
              "https://doi.org/10.1038/nbt.3437"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s10147-016-0957-1", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1042368319", 
              "https://doi.org/10.1007/s10147-016-0957-1"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nprot.2016.095", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1004211338", 
              "https://doi.org/10.1038/nprot.2016.095"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/srep23770", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1014900039", 
              "https://doi.org/10.1038/srep23770"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/s41467-017-00738-7", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1091951525", 
              "https://doi.org/10.1038/s41467-017-00738-7"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nature09589", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1049984554", 
              "https://doi.org/10.1038/nature09589"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nrm2183", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1049496060", 
              "https://doi.org/10.1038/nrm2183"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nature21724", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1084128609", 
              "https://doi.org/10.1038/nature21724"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1186/s13059-014-0554-4", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1014314357", 
              "https://doi.org/10.1186/s13059-014-0554-4"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/s41591-018-0096-5", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1105391092", 
              "https://doi.org/10.1038/s41591-018-0096-5"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/onc.2016.184", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1024209045", 
              "https://doi.org/10.1038/onc.2016.184"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1186/s13059-014-0550-8", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1015222646", 
              "https://doi.org/10.1186/s13059-014-0550-8"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nature09504", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1001851540", 
              "https://doi.org/10.1038/nature09504"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nature14888", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1036615307", 
              "https://doi.org/10.1038/nature14888"
            ], 
            "type": "CreativeWork"
          }
        ], 
        "datePublished": "2021-07-15", 
        "datePublishedReg": "2021-07-15", 
        "description": "Angiogenesis underlies development, physiology and pathogenesis of cancer, eye and cardiovascular diseases. Inhibiting aberrant angiogenesis using anti-angiogenic therapy (AAT) has been successful in the clinical treatment of cancer and eye diseases. However, resistance to AAT inevitably occurs and its molecular basis remains poorly understood. Here, we uncover molecular modifiers of the blood endothelial cell (EC) response to a widely used AAT bevacizumab by performing a pooled genetic screen using three-dimensional microcarrier-based cell culture and CRISPR\u2013Cas9. Functional inhibition of the epigenetic reader BET family of proteins BRD2/3/4 shows unexpected mitigating effects on EC survival and/or proliferation upon VEGFA blockade. Moreover, transcriptomic and pathway analyses reveal an interaction between epigenetic regulation and anti-angiogenesis, which may affect chromosomal structure and activity in ECs via the cell cycle regulator CDC25B phosphatase. Collectively, our findings provide insight into epigenetic regulation of the EC response to VEGFA blockade and may facilitate development of quality biomarkers and strategies for overcoming resistance to AAT.", 
        "genre": "article", 
        "id": "sg:pub.10.1038/s42003-021-02397-3", 
        "isAccessibleForFree": true, 
        "isFundedItemOf": [
          {
            "id": "sg:grant.8853092", 
            "type": "MonetaryGrant"
          }, 
          {
            "id": "sg:grant.8853335", 
            "type": "MonetaryGrant"
          }, 
          {
            "id": "sg:grant.7875648", 
            "type": "MonetaryGrant"
          }
        ], 
        "isPartOf": [
          {
            "id": "sg:journal.1300829", 
            "issn": [
              "2399-3642"
            ], 
            "name": "Communications Biology", 
            "publisher": "Springer Nature", 
            "type": "Periodical"
          }, 
          {
            "issueNumber": "1", 
            "type": "PublicationIssue"
          }, 
          {
            "type": "PublicationVolume", 
            "volumeNumber": "4"
          }
        ], 
        "keywords": [
          "epigenetic regulation", 
          "anti-angiogenic therapy", 
          "pooled genetic screens", 
          "genetic screen", 
          "CDC25B phosphatase", 
          "pathogenesis of cancer", 
          "chromosomal structure", 
          "CRISPR screening", 
          "epigenetic readers", 
          "epigenetic interactions", 
          "molecular basis", 
          "pathway analysis", 
          "endothelial cell responses", 
          "VEGFA blockade", 
          "EC survival", 
          "quality biomarkers", 
          "functional inhibition", 
          "cell cultures", 
          "aberrant angiogenesis", 
          "regulation", 
          "EC response", 
          "cardiovascular disease", 
          "eye disease", 
          "angiogenesis", 
          "cell responses", 
          "clinical treatment", 
          "CRISPR", 
          "microcarrier-based cell culture", 
          "therapy", 
          "phosphatase", 
          "cancer", 
          "physiology", 
          "disease", 
          "VEGFA", 
          "molecular modifiers", 
          "proliferation", 
          "interaction", 
          "family", 
          "resistance", 
          "screen", 
          "response", 
          "inhibition", 
          "bevacizumab", 
          "blockade", 
          "pathogenesis", 
          "insights", 
          "development", 
          "biomarkers", 
          "survival", 
          "treatment", 
          "eyes", 
          "activity", 
          "modifiers", 
          "culture", 
          "screening", 
          "findings", 
          "basis", 
          "structure", 
          "analysis", 
          "EC", 
          "effect", 
          "strategies", 
          "show", 
          "readers"
        ], 
        "name": "Three-dimensional CRISPR screening reveals epigenetic interaction with anti-angiogenic therapy", 
        "pagination": "878", 
        "productId": [
          {
            "name": "dimensions_id", 
            "type": "PropertyValue", 
            "value": [
              "pub.1139694358"
            ]
          }, 
          {
            "name": "doi", 
            "type": "PropertyValue", 
            "value": [
              "10.1038/s42003-021-02397-3"
            ]
          }, 
          {
            "name": "pubmed_id", 
            "type": "PropertyValue", 
            "value": [
              "34267311"
            ]
          }
        ], 
        "sameAs": [
          "https://doi.org/10.1038/s42003-021-02397-3", 
          "https://app.dimensions.ai/details/publication/pub.1139694358"
        ], 
        "sdDataset": "articles", 
        "sdDatePublished": "2022-09-02T16:06", 
        "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
        "sdPublisher": {
          "name": "Springer Nature - SN SciGraph project", 
          "type": "Organization"
        }, 
        "sdSource": "s3://com-springernature-scigraph/baseset/20220902/entities/gbq_results/article/article_898.jsonl", 
        "type": "ScholarlyArticle", 
        "url": "https://doi.org/10.1038/s42003-021-02397-3"
      }
    ]
     

    Download the RDF metadata as:  json-ld nt turtle xml License info

    HOW TO GET THIS DATA PROGRAMMATICALLY:

    JSON-LD is a popular format for linked data which is fully compatible with JSON.

    curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/s42003-021-02397-3'

    N-Triples is a line-based linked data format ideal for batch operations.

    curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/s42003-021-02397-3'

    Turtle is a human-readable linked data format.

    curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/s42003-021-02397-3'

    RDF/XML is a standard XML format for linked data.

    curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/s42003-021-02397-3'


     

    This table displays all metadata directly associated to this object as RDF triples.

    377 TRIPLES      21 PREDICATES      122 URIs      87 LITERALS      13 BLANK NODES

    Subject Predicate Object
    1 sg:pub.10.1038/s42003-021-02397-3 schema:about N200f698ffa434157a16dcda3b4bb134d
    2 N280c1933bf7b4764bc3884b107b628d0
    3 N6e03e232fc9c49e582d6073c8d3a8adb
    4 N6ec143c8438f4b82a6acccb0eef51525
    5 Nbd7ad4bd9cf24c8589e8e4ef05bf5fad
    6 Nfc49be0711304912ba8a41f45da70532
    7 anzsrc-for:06
    8 anzsrc-for:0601
    9 schema:author N022858c6647f4ccaafc1f9258dc3e338
    10 schema:citation sg:pub.10.1007/s10147-016-0957-1
    11 sg:pub.10.1007/s10456-017-9551-z
    12 sg:pub.10.1038/nature09504
    13 sg:pub.10.1038/nature09589
    14 sg:pub.10.1038/nature10509
    15 sg:pub.10.1038/nature14888
    16 sg:pub.10.1038/nature16508
    17 sg:pub.10.1038/nature21724
    18 sg:pub.10.1038/nbt.2842
    19 sg:pub.10.1038/nbt.3437
    20 sg:pub.10.1038/ncomms12624
    21 sg:pub.10.1038/nprot.2016.095
    22 sg:pub.10.1038/nprot.2017.016
    23 sg:pub.10.1038/nrc.2017.51
    24 sg:pub.10.1038/nrd.2015.17
    25 sg:pub.10.1038/nrg3899
    26 sg:pub.10.1038/nrm.2017.36
    27 sg:pub.10.1038/nrm2183
    28 sg:pub.10.1038/onc.2016.184
    29 sg:pub.10.1038/s41467-017-00405-x
    30 sg:pub.10.1038/s41467-017-00738-7
    31 sg:pub.10.1038/s41467-017-01645-7
    32 sg:pub.10.1038/s41591-018-0096-5
    33 sg:pub.10.1038/srep23770
    34 sg:pub.10.1186/gb-2014-15-2-r29
    35 sg:pub.10.1186/s13059-014-0550-8
    36 sg:pub.10.1186/s13059-014-0554-4
    37 schema:datePublished 2021-07-15
    38 schema:datePublishedReg 2021-07-15
    39 schema:description Angiogenesis underlies development, physiology and pathogenesis of cancer, eye and cardiovascular diseases. Inhibiting aberrant angiogenesis using anti-angiogenic therapy (AAT) has been successful in the clinical treatment of cancer and eye diseases. However, resistance to AAT inevitably occurs and its molecular basis remains poorly understood. Here, we uncover molecular modifiers of the blood endothelial cell (EC) response to a widely used AAT bevacizumab by performing a pooled genetic screen using three-dimensional microcarrier-based cell culture and CRISPR–Cas9. Functional inhibition of the epigenetic reader BET family of proteins BRD2/3/4 shows unexpected mitigating effects on EC survival and/or proliferation upon VEGFA blockade. Moreover, transcriptomic and pathway analyses reveal an interaction between epigenetic regulation and anti-angiogenesis, which may affect chromosomal structure and activity in ECs via the cell cycle regulator CDC25B phosphatase. Collectively, our findings provide insight into epigenetic regulation of the EC response to VEGFA blockade and may facilitate development of quality biomarkers and strategies for overcoming resistance to AAT.
    40 schema:genre article
    41 schema:isAccessibleForFree true
    42 schema:isPartOf N2710645dec954502a2d0db37d5e9feb9
    43 Nac7cf943f81946c2ae1bbc2c05fa081f
    44 sg:journal.1300829
    45 schema:keywords CDC25B phosphatase
    46 CRISPR
    47 CRISPR screening
    48 EC
    49 EC response
    50 EC survival
    51 VEGFA
    52 VEGFA blockade
    53 aberrant angiogenesis
    54 activity
    55 analysis
    56 angiogenesis
    57 anti-angiogenic therapy
    58 basis
    59 bevacizumab
    60 biomarkers
    61 blockade
    62 cancer
    63 cardiovascular disease
    64 cell cultures
    65 cell responses
    66 chromosomal structure
    67 clinical treatment
    68 culture
    69 development
    70 disease
    71 effect
    72 endothelial cell responses
    73 epigenetic interactions
    74 epigenetic readers
    75 epigenetic regulation
    76 eye disease
    77 eyes
    78 family
    79 findings
    80 functional inhibition
    81 genetic screen
    82 inhibition
    83 insights
    84 interaction
    85 microcarrier-based cell culture
    86 modifiers
    87 molecular basis
    88 molecular modifiers
    89 pathogenesis
    90 pathogenesis of cancer
    91 pathway analysis
    92 phosphatase
    93 physiology
    94 pooled genetic screens
    95 proliferation
    96 quality biomarkers
    97 readers
    98 regulation
    99 resistance
    100 response
    101 screen
    102 screening
    103 show
    104 strategies
    105 structure
    106 survival
    107 therapy
    108 treatment
    109 schema:name Three-dimensional CRISPR screening reveals epigenetic interaction with anti-angiogenic therapy
    110 schema:pagination 878
    111 schema:productId N05beb9a8a4be4d6eaf2cfb4215a1c154
    112 N146a5386d8ee43cb84b09c0d4de28ae7
    113 N76ee91374f4f47a7b3c3345f68bba4f2
    114 schema:sameAs https://app.dimensions.ai/details/publication/pub.1139694358
    115 https://doi.org/10.1038/s42003-021-02397-3
    116 schema:sdDatePublished 2022-09-02T16:06
    117 schema:sdLicense https://scigraph.springernature.com/explorer/license/
    118 schema:sdPublisher Nc1c547c591b94339b3beaf5db7be1f09
    119 schema:url https://doi.org/10.1038/s42003-021-02397-3
    120 sgo:license sg:explorer/license/
    121 sgo:sdDataset articles
    122 rdf:type schema:ScholarlyArticle
    123 N022858c6647f4ccaafc1f9258dc3e338 rdf:first sg:person.010730706253.43
    124 rdf:rest N059c91cbb44741b19253b8449ee023a1
    125 N059c91cbb44741b19253b8449ee023a1 rdf:first sg:person.01110546207.52
    126 rdf:rest N6cdc623ac28043a9a0de7b995656d865
    127 N05beb9a8a4be4d6eaf2cfb4215a1c154 schema:name doi
    128 schema:value 10.1038/s42003-021-02397-3
    129 rdf:type schema:PropertyValue
    130 N146a5386d8ee43cb84b09c0d4de28ae7 schema:name dimensions_id
    131 schema:value pub.1139694358
    132 rdf:type schema:PropertyValue
    133 N200f698ffa434157a16dcda3b4bb134d schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    134 schema:name Epigenesis, Genetic
    135 rdf:type schema:DefinedTerm
    136 N253df188f3f54ec9a0c38f7034d4f44f rdf:first sg:person.013455005252.42
    137 rdf:rest N631df9997ccb4b208a5690a356e85dd5
    138 N2710645dec954502a2d0db37d5e9feb9 schema:volumeNumber 4
    139 rdf:type schema:PublicationVolume
    140 N2741fadae7f746a8a9697ecad691cdfb rdf:first sg:person.0631434345.27
    141 rdf:rest Nbde67b0540f04d948d3635958892372e
    142 N280c1933bf7b4764bc3884b107b628d0 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    143 schema:name Bevacizumab
    144 rdf:type schema:DefinedTerm
    145 N47f520407b944141b78892f43b86c015 rdf:first sg:person.01125006176.31
    146 rdf:rest Ne8e1de805866455cb140a9399df4fbee
    147 N631df9997ccb4b208a5690a356e85dd5 rdf:first sg:person.01270035270.04
    148 rdf:rest Nf8eb77761b284e3f8605385310135796
    149 N6cdc623ac28043a9a0de7b995656d865 rdf:first sg:person.0765352520.03
    150 rdf:rest Ne5f80f91aa134a11ae6ef80395433315
    151 N6e03e232fc9c49e582d6073c8d3a8adb schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    152 schema:name Endothelial Cells
    153 rdf:type schema:DefinedTerm
    154 N6ec143c8438f4b82a6acccb0eef51525 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    155 schema:name Angiogenesis Inhibitors
    156 rdf:type schema:DefinedTerm
    157 N76ee91374f4f47a7b3c3345f68bba4f2 schema:name pubmed_id
    158 schema:value 34267311
    159 rdf:type schema:PropertyValue
    160 Nac7cf943f81946c2ae1bbc2c05fa081f schema:issueNumber 1
    161 rdf:type schema:PublicationIssue
    162 Nbd7ad4bd9cf24c8589e8e4ef05bf5fad schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    163 schema:name Clustered Regularly Interspaced Short Palindromic Repeats
    164 rdf:type schema:DefinedTerm
    165 Nbde67b0540f04d948d3635958892372e rdf:first sg:person.014226777041.19
    166 rdf:rest N253df188f3f54ec9a0c38f7034d4f44f
    167 Nc1c547c591b94339b3beaf5db7be1f09 schema:name Springer Nature - SN SciGraph project
    168 rdf:type schema:Organization
    169 Ndbe0a6d6998c4381afc03e6d878312a1 rdf:first sg:person.013077405605.23
    170 rdf:rest N47f520407b944141b78892f43b86c015
    171 Ne5f80f91aa134a11ae6ef80395433315 rdf:first sg:person.016025604012.02
    172 rdf:rest Ndbe0a6d6998c4381afc03e6d878312a1
    173 Ne8e1de805866455cb140a9399df4fbee rdf:first sg:person.012152756657.54
    174 rdf:rest N2741fadae7f746a8a9697ecad691cdfb
    175 Nf8eb77761b284e3f8605385310135796 rdf:first sg:person.01221722070.50
    176 rdf:rest rdf:nil
    177 Nfc49be0711304912ba8a41f45da70532 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    178 schema:name Blood
    179 rdf:type schema:DefinedTerm
    180 anzsrc-for:06 schema:inDefinedTermSet anzsrc-for:
    181 schema:name Biological Sciences
    182 rdf:type schema:DefinedTerm
    183 anzsrc-for:0601 schema:inDefinedTermSet anzsrc-for:
    184 schema:name Biochemistry and Cell Biology
    185 rdf:type schema:DefinedTerm
    186 sg:grant.7875648 http://pending.schema.org/fundedItem sg:pub.10.1038/s42003-021-02397-3
    187 rdf:type schema:MonetaryGrant
    188 sg:grant.8853092 http://pending.schema.org/fundedItem sg:pub.10.1038/s42003-021-02397-3
    189 rdf:type schema:MonetaryGrant
    190 sg:grant.8853335 http://pending.schema.org/fundedItem sg:pub.10.1038/s42003-021-02397-3
    191 rdf:type schema:MonetaryGrant
    192 sg:journal.1300829 schema:issn 2399-3642
    193 schema:name Communications Biology
    194 schema:publisher Springer Nature
    195 rdf:type schema:Periodical
    196 sg:person.010730706253.43 schema:affiliation grid-institutes:grid.415224.4
    197 schema:familyName He
    198 schema:givenName Michael Y.
    199 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.010730706253.43
    200 rdf:type schema:Person
    201 sg:person.01110546207.52 schema:affiliation grid-institutes:grid.1055.1
    202 schema:familyName Halford
    203 schema:givenName Michael M.
    204 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01110546207.52
    205 rdf:type schema:Person
    206 sg:person.01125006176.31 schema:affiliation grid-institutes:grid.1008.9
    207 schema:familyName Coultas
    208 schema:givenName Leigh
    209 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01125006176.31
    210 rdf:type schema:Person
    211 sg:person.012152756657.54 schema:affiliation grid-institutes:grid.1055.1
    212 schema:familyName Thio
    213 schema:givenName Niko
    214 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.012152756657.54
    215 rdf:type schema:Person
    216 sg:person.01221722070.50 schema:affiliation grid-institutes:grid.1008.9
    217 schema:familyName Stacker
    218 schema:givenName Steven A.
    219 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01221722070.50
    220 rdf:type schema:Person
    221 sg:person.01270035270.04 schema:affiliation grid-institutes:grid.1073.5
    222 schema:familyName Achen
    223 schema:givenName Marc G.
    224 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01270035270.04
    225 rdf:type schema:Person
    226 sg:person.013077405605.23 schema:affiliation grid-institutes:grid.249878.8
    227 schema:familyName Grant
    228 schema:givenName Zoe L.
    229 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.013077405605.23
    230 rdf:type schema:Person
    231 sg:person.013455005252.42 schema:affiliation grid-institutes:grid.1055.1
    232 schema:familyName Dawson
    233 schema:givenName Mark A.
    234 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.013455005252.42
    235 rdf:type schema:Person
    236 sg:person.014226777041.19 schema:affiliation grid-institutes:grid.1055.1
    237 schema:familyName Chan
    238 schema:givenName Yih-Chih
    239 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.014226777041.19
    240 rdf:type schema:Person
    241 sg:person.016025604012.02 schema:affiliation grid-institutes:grid.1008.9
    242 schema:familyName Roy
    243 schema:givenName James P.
    244 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.016025604012.02
    245 rdf:type schema:Person
    246 sg:person.0631434345.27 schema:affiliation grid-institutes:grid.1002.3
    247 schema:familyName Gilan
    248 schema:givenName Omer
    249 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0631434345.27
    250 rdf:type schema:Person
    251 sg:person.0765352520.03 schema:affiliation grid-institutes:grid.1008.9
    252 schema:familyName Liu
    253 schema:givenName Ruofei
    254 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0765352520.03
    255 rdf:type schema:Person
    256 sg:pub.10.1007/s10147-016-0957-1 schema:sameAs https://app.dimensions.ai/details/publication/pub.1042368319
    257 https://doi.org/10.1007/s10147-016-0957-1
    258 rdf:type schema:CreativeWork
    259 sg:pub.10.1007/s10456-017-9551-z schema:sameAs https://app.dimensions.ai/details/publication/pub.1084513520
    260 https://doi.org/10.1007/s10456-017-9551-z
    261 rdf:type schema:CreativeWork
    262 sg:pub.10.1038/nature09504 schema:sameAs https://app.dimensions.ai/details/publication/pub.1001851540
    263 https://doi.org/10.1038/nature09504
    264 rdf:type schema:CreativeWork
    265 sg:pub.10.1038/nature09589 schema:sameAs https://app.dimensions.ai/details/publication/pub.1049984554
    266 https://doi.org/10.1038/nature09589
    267 rdf:type schema:CreativeWork
    268 sg:pub.10.1038/nature10509 schema:sameAs https://app.dimensions.ai/details/publication/pub.1026728956
    269 https://doi.org/10.1038/nature10509
    270 rdf:type schema:CreativeWork
    271 sg:pub.10.1038/nature14888 schema:sameAs https://app.dimensions.ai/details/publication/pub.1036615307
    272 https://doi.org/10.1038/nature14888
    273 rdf:type schema:CreativeWork
    274 sg:pub.10.1038/nature16508 schema:sameAs https://app.dimensions.ai/details/publication/pub.1024399927
    275 https://doi.org/10.1038/nature16508
    276 rdf:type schema:CreativeWork
    277 sg:pub.10.1038/nature21724 schema:sameAs https://app.dimensions.ai/details/publication/pub.1084128609
    278 https://doi.org/10.1038/nature21724
    279 rdf:type schema:CreativeWork
    280 sg:pub.10.1038/nbt.2842 schema:sameAs https://app.dimensions.ai/details/publication/pub.1038520013
    281 https://doi.org/10.1038/nbt.2842
    282 rdf:type schema:CreativeWork
    283 sg:pub.10.1038/nbt.3437 schema:sameAs https://app.dimensions.ai/details/publication/pub.1014083513
    284 https://doi.org/10.1038/nbt.3437
    285 rdf:type schema:CreativeWork
    286 sg:pub.10.1038/ncomms12624 schema:sameAs https://app.dimensions.ai/details/publication/pub.1050269937
    287 https://doi.org/10.1038/ncomms12624
    288 rdf:type schema:CreativeWork
    289 sg:pub.10.1038/nprot.2016.095 schema:sameAs https://app.dimensions.ai/details/publication/pub.1004211338
    290 https://doi.org/10.1038/nprot.2016.095
    291 rdf:type schema:CreativeWork
    292 sg:pub.10.1038/nprot.2017.016 schema:sameAs https://app.dimensions.ai/details/publication/pub.1084129553
    293 https://doi.org/10.1038/nprot.2017.016
    294 rdf:type schema:CreativeWork
    295 sg:pub.10.1038/nrc.2017.51 schema:sameAs https://app.dimensions.ai/details/publication/pub.1090661850
    296 https://doi.org/10.1038/nrc.2017.51
    297 rdf:type schema:CreativeWork
    298 sg:pub.10.1038/nrd.2015.17 schema:sameAs https://app.dimensions.ai/details/publication/pub.1052866965
    299 https://doi.org/10.1038/nrd.2015.17
    300 rdf:type schema:CreativeWork
    301 sg:pub.10.1038/nrg3899 schema:sameAs https://app.dimensions.ai/details/publication/pub.1013619504
    302 https://doi.org/10.1038/nrg3899
    303 rdf:type schema:CreativeWork
    304 sg:pub.10.1038/nrm.2017.36 schema:sameAs https://app.dimensions.ai/details/publication/pub.1085575671
    305 https://doi.org/10.1038/nrm.2017.36
    306 rdf:type schema:CreativeWork
    307 sg:pub.10.1038/nrm2183 schema:sameAs https://app.dimensions.ai/details/publication/pub.1049496060
    308 https://doi.org/10.1038/nrm2183
    309 rdf:type schema:CreativeWork
    310 sg:pub.10.1038/onc.2016.184 schema:sameAs https://app.dimensions.ai/details/publication/pub.1024209045
    311 https://doi.org/10.1038/onc.2016.184
    312 rdf:type schema:CreativeWork
    313 sg:pub.10.1038/s41467-017-00405-x schema:sameAs https://app.dimensions.ai/details/publication/pub.1091331666
    314 https://doi.org/10.1038/s41467-017-00405-x
    315 rdf:type schema:CreativeWork
    316 sg:pub.10.1038/s41467-017-00738-7 schema:sameAs https://app.dimensions.ai/details/publication/pub.1091951525
    317 https://doi.org/10.1038/s41467-017-00738-7
    318 rdf:type schema:CreativeWork
    319 sg:pub.10.1038/s41467-017-01645-7 schema:sameAs https://app.dimensions.ai/details/publication/pub.1092730297
    320 https://doi.org/10.1038/s41467-017-01645-7
    321 rdf:type schema:CreativeWork
    322 sg:pub.10.1038/s41591-018-0096-5 schema:sameAs https://app.dimensions.ai/details/publication/pub.1105391092
    323 https://doi.org/10.1038/s41591-018-0096-5
    324 rdf:type schema:CreativeWork
    325 sg:pub.10.1038/srep23770 schema:sameAs https://app.dimensions.ai/details/publication/pub.1014900039
    326 https://doi.org/10.1038/srep23770
    327 rdf:type schema:CreativeWork
    328 sg:pub.10.1186/gb-2014-15-2-r29 schema:sameAs https://app.dimensions.ai/details/publication/pub.1045312009
    329 https://doi.org/10.1186/gb-2014-15-2-r29
    330 rdf:type schema:CreativeWork
    331 sg:pub.10.1186/s13059-014-0550-8 schema:sameAs https://app.dimensions.ai/details/publication/pub.1015222646
    332 https://doi.org/10.1186/s13059-014-0550-8
    333 rdf:type schema:CreativeWork
    334 sg:pub.10.1186/s13059-014-0554-4 schema:sameAs https://app.dimensions.ai/details/publication/pub.1014314357
    335 https://doi.org/10.1186/s13059-014-0554-4
    336 rdf:type schema:CreativeWork
    337 grid-institutes:grid.1002.3 schema:alternateName Australian Centre for Blood Diseases, Monash University, Melbourne, VIC, Australia
    338 schema:name Australian Centre for Blood Diseases, Monash University, Melbourne, VIC, Australia
    339 Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC, Australia
    340 Translational Haematology Program, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
    341 rdf:type schema:Organization
    342 grid-institutes:grid.1008.9 schema:alternateName Department of Medical Biology, The University of Melbourne, Parkville, VIC, Australia
    343 Department of Surgery, Royal Melbourne Hospital, The University of Melbourne, Parkville, VIC, Australia
    344 Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC, Australia
    345 schema:name Department of Medical Biology, The University of Melbourne, Parkville, VIC, Australia
    346 Department of Surgery, Royal Melbourne Hospital, The University of Melbourne, Parkville, VIC, Australia
    347 Epigenetics and Development Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia
    348 Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC, Australia
    349 Tumour Angiogenesis and Microenvironment Program, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
    350 rdf:type schema:Organization
    351 grid-institutes:grid.1055.1 schema:alternateName Bioinformatics Core, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
    352 Department of Haematology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
    353 Translational Haematology Program, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
    354 Tumour Angiogenesis and Microenvironment Program, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
    355 schema:name Bioinformatics Core, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
    356 Centre for Cancer Research, The University of Melbourne, Parkville, VIC, Australia
    357 Department of Haematology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
    358 Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC, Australia
    359 Translational Haematology Program, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
    360 Tumour Angiogenesis and Microenvironment Program, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
    361 rdf:type schema:Organization
    362 grid-institutes:grid.1073.5 schema:alternateName St Vincent’s Institute of Medical Research, Melbourne, VIC, Australia
    363 schema:name Department of Surgery, Royal Melbourne Hospital, The University of Melbourne, Parkville, VIC, Australia
    364 Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC, Australia
    365 St Vincent’s Institute of Medical Research, Melbourne, VIC, Australia
    366 Tumour Angiogenesis and Microenvironment Program, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
    367 rdf:type schema:Organization
    368 grid-institutes:grid.249878.8 schema:alternateName Gladstone Institutes, San Francisco, CA, USA
    369 schema:name Department of Medical Biology, The University of Melbourne, Parkville, VIC, Australia
    370 Epigenetics and Development Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia
    371 Gladstone Institutes, San Francisco, CA, USA
    372 rdf:type schema:Organization
    373 grid-institutes:grid.415224.4 schema:alternateName Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
    374 schema:name Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
    375 Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC, Australia
    376 Tumour Angiogenesis and Microenvironment Program, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
    377 rdf:type schema:Organization
     




    Preview window. Press ESC to close (or click here)


    ...