@prefix adms: <http://www.w3.org/ns/adms#> .
@prefix dcat: <http://www.w3.org/ns/dcat#> .
@prefix dcatap: <http://data.europa.eu/r5r/> .
@prefix dct: <http://purl.org/dc/terms/> .
@prefix foaf: <http://xmlns.com/foaf/0.1/> .
@prefix healthdcatap: <http://healthdataportal.eu/ns/health#> .
@prefix rdfs: <http://www.w3.org/2000/01/rdf-schema#> .
@prefix vcard: <http://www.w3.org/2006/vcard/ns#> .
@prefix xsd: <http://www.w3.org/2001/XMLSchema#> .

<https://fdp.heart-institute.nl/dataset/e6ea8de6-24a9-4341-9de5-121fafe1c1ed> a dcat:Dataset ;
    dcatap:applicableLegislation <http://data.europa.eu/eli/reg/2025/327/oj> ;
    healthdcatap:maxTypicalAge "75"^^xsd:nonNegativeInteger ;
    healthdcatap:minTypicalAge "1"^^xsd:nonNegativeInteger ;
    healthdcatap:populationCoverage "collection type: Cohort,Disease specific,Image collection,Longitudinal,Sample collection | disease: Cardiomyopathy - Other cardiomyopathies | data categories: Biological samples,Imaging data,Medical records,Physiological/Biochemical measurements,Survey data | materials: cDNA / mRNA,DNA,Plasma,RNA,Serum,Tissue, cryo preserved,Tissue, paraffin preserved,Whole Blood | omics: Genomics,Metabolomics,Proteomics,Transcriptomics | imaging: Y | sex: Female,Male"@nl ;
    dct:accessRights <http://publications.europa.eu/resource/authority/access-right/RESTRICTED> ;
    dct:creator [ a foaf:Agent ;
            dct:identifier "DCVA" ;
            vcard:hasEmail <mailto:info@dcvalliance.nl> ;
            foaf:homepage <https://www.dcvalliance.nl/> ;
            foaf:name "Dutch Cardiovascular Alliance (DCVA)" ] ;
    dct:description ""@en,
        "Inherited cardiomyopathies (CM) are clinically heterogeneous: age of onset and disease-severity differ greatly between patients with the exact same gene mutation. The mechanisms that underlie the variation in disease susceptibility are unknown.  Pilot data of DOSIS suggest an important role for secondary disease-modifiers such as additional (epi)genetic variations, environmental disease triggers, and an age-related decline in protein quality control (PQC). The PQC system prevents onset of CM by suppressing the accumulation of toxic proteins in cardiomyocytes. Moreover, CM severity is attenuated by the stimulation of protein degradation pathways. Thus, a healthy PQC system keeps mutant expression below the toxic dose. In addition, mutation location in a gene may determine disease susceptibility due to specific mutation-induced changes in protein structure, which alter PQC recognition, and affect incorporation into the sarcomere.  Hypothesis: the clinical variability in CM is determined by (1) interplay between (epi)genetic and ageing-induced environmental factors (burden); (2) status of the PQC system (coping mechanisms); (3) mutation location.  Aims:   1.	Identify (epi)genetic modifiers influencing the CM phenotype in individuals carrying a sarcomeric mutation.  2.	Elucidate derailment of the PQC system as determinant of cellular toxicity in CM.  3.	Establish the toxic effect of mutants with respect to protein dose and mutation location.  4.	Obtain proof of concept for age-dependent secondary disease-modifiers as key players in protein toxicity of CM mutations and test novel pharmacological interventions.  DOSIS is directed at understanding the path a mutation needs to travel to become toxic, and at testing novel therapies in experimental model systems."@nl ;
    dct:identifier "DCVA-039" ;
    dct:issued "2015-12-01T00:00:00+00:00"^^xsd:dateTime ;
    dct:language <http://id.loc.gov/vocabulary/iso639-1/en> ;
    dct:modified "2026-04-17T10:32:31.936979"^^xsd:dateTime ;
    dct:provenance [ a dct:ProvenanceStatement ;
            rdfs:label ""@en,
                ""@nl ] ;
    dct:publisher [ a foaf:Agent ;
            dct:identifier "DCVA" ;
            vcard:hasEmail <mailto:info@dcvalliance.nl> ;
            foaf:homepage <https://www.dcvalliance.nl/> ;
            foaf:name "Dutch Cardiovascular Alliance (DCVA)" ] ;
    dct:spatial <http://publications.europa.eu/resource/authority/country/NLD> ;
    dct:temporal [ a dct:PeriodOfTime ;
            dcat:endDate "2020-11-30T00:00:00+00:00"^^xsd:dateTime ;
            dcat:startDate "2015-12-01T00:00:00+00:00"^^xsd:dateTime ] ;
    dct:title ""@en,
        "DETERMINANTS OF SUSCEPTIBILITY IN INHERITED CARDIOMYOPATHY: TOWARDS NOVEL THERAPEUTIC APPROACHES"@nl ;
    adms:versionNotes ""@en,
        ""@nl ;
    dcat:contactPoint [ a vcard:Kind ;
            vcard:fn "DCVA" ;
            vcard:hasEmail <mailto:info@dcvalliance.nl> ;
            vcard:hasURL <['https://www.dcvalliance.nl/']> ] ;
    dcat:keyword "Biological samples"@nl,
        "Cardiomyopathy - Other cardiomyopathies"@nl,
        "Cohort"@nl,
        "DNA"@nl,
        "DOSIS"@nl,
        "Disease specific"@nl,
        "Female"@nl,
        "Genomics"@nl,
        "Image collection"@nl,
        "Imaging data"@nl,
        "Longitudinal"@nl,
        "Male"@nl,
        "Medical records"@nl,
        "Metabolomics"@nl,
        "Physiological Biochemical measurements"@nl,
        "Plasma"@nl,
        "Proteomics"@nl,
        "RNA"@nl,
        "Sample collection"@nl,
        "Serum"@nl,
        "Survey data"@nl,
        "Tissue"@nl,
        "Transcriptomics"@nl,
        "Whole Blood"@nl,
        "cDNA   mRNA"@nl,
        "cryo preserved"@nl,
        "paraffin preserved"@nl ;
    dcat:qualifiedAttribution [ a dcat:Attribution ;
            dcat:agent [ a foaf:Agent,
                        foaf:Organization ;
                    dct:identifier "DCVA" ;
                    foaf:homepage <https://www.dcvalliance.nl/> ;
                    foaf:mbox <mailto:info@dcvalliance.nl> ;
                    foaf:name "Dutch Cardiovascular Alliance (DCVA)" ] ] ;
    dcat:theme <http://publications.europa.eu/resource/authority/data-theme/HEAL> .

<http://data.europa.eu/eli/reg/2025/327/oj> a <http://data.europa.eu/eli/ontology#LegalResource> .

<http://id.loc.gov/vocabulary/iso639-1/en> a dct:LinguisticSystem .

<http://publications.europa.eu/resource/authority/access-right/RESTRICTED> a dct:RightsStatement .

<http://publications.europa.eu/resource/authority/country/NLD> a dct:Location .