Pre-cancer atlases of cutaneous and hematologic origin (PATCH Center)
皮肤和血液来源的癌前图谱(PATCH 中心)
基本信息
- 批准号:10252281
- 负责人:
- 金额:$ 97.48万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-09-30 至 2024-08-31
- 项目状态:已结题
- 来源:
- 关键词:AntibodiesAreaAtlasesAutomobile DrivingBackBenchmarkingBiological AssayBiological Specimen BanksBiopsyBloodBone MarrowCancer HistologyCell LineCellsCellular MorphologyClinicalClinical DataCodeCollaborationsCollectionCommunicationComplexComputer Vision SystemsComputersComputing MethodologiesCutaneousDNADNA sequencingDataData AnalysesData ScientistDatabasesDevelopmentDiagnosisDiseaseDisease ProgressionEngineeringEnrollmentEnsureFAIR principlesFee-for-Service PlansFlow CytometryFormalinFoundationsFreezingFundingGeneticGenomicsGenotypeGoalsHeadHealthHematologyHematopoiesisHematopoietic NeoplasmsHistologicHumanImageImmuneImmunofluorescence ImmunologicIncidenceIndividualIndustrializationLaboratoriesLeadLeadershipLesionLifeLinkLiquid substanceMalignant - descriptorMalignant NeoplasmsMapsMetadataMethodsMolecularMonitorMyeloproliferative diseaseOncologistParaffin EmbeddingPathologistPatientsPerformancePeriodicityPharmacologyPhasePhysiciansPlayPositioning AttributePrevention strategyPrevention therapyPrevention trialProspective cohortProtocols documentationReadabilityReagentResearch PersonnelRiskRunningSamplingScientistServicesSkin CancerSoftware EngineeringSolidSpecimenStandardizationStromal CellsSurgeonSystemTechnologyTestingTimeTime Series AnalysisTissue BanksTissue imagingTissuesTumor TissueValidationVisualizationVisualization softwareWorkalgorithm developmentbasecancer invasivenesscell typecohortcomputing resourcescrowdsourcingdata acquisitiondata standardsdata submissiondata visualizationdeep neural networkdimensional analysisfeature extractiongenetic analysishigh dimensionalityhigh riskimage visualizationindividual patientindividualized preventioninsightknowledge baselaser capture microdissectionmachine learning methodmelanomamembermultiplexed imagingneoplasticnew technologypremalignantpreventprevention clinical trialprospectiveskin lesiontumor microenvironment
项目摘要
SUMMARY-ABSTRACT
The overall goal of this proposal is to construct two pre-cancer atlases (PCAs) from highly accessible pre-
malignant diseases that impose high burdens on human health (i) one focused on progression of pre-
melanoma lesions to invasive cancer and (ii) a second on progression from clonal hematopoiesis (CHIP) to
myeloid neoplasms. Both of these involve expansion of specific clones in normal and diseased niches as
shaped by complex interactions among immune and pre-cancer cells. The resulting Atlases developed by the
Center for Pre-cancer Atlases of Cutaneous and Hematologic Origin (PATCH Center) present complementary
technical challenges, avenues to scientific discovery, and opportunities for the development of precision
prevention strategies and therapies. The key goal in both cases is to precisely delineate and understand the
molecular mechanisms driving progression from pre-malignant to malignant disease, to identify high risk
individuals, prioritize particular therapies and serve as the foundation for precision prevention clinical trials.
This will be achieved by integrated characterization of single cell genotype and cell states using high-plex
tissue imaging and omic characterization of cross-sectional and well-controlled longitudinal patient cohorts.
Aim 1 will establish an administrative core responsible for scientific management of the Center, coordination
with HTAN members and dissemination of Atlases under the direction of an internal Executive Committee with
three subcommittees. Aim 2 will establish a Biospecimen Unit under the leadership of pathologists, oncologists
and a surgeon. The DFCI Pasquarello Tissue Repository will provide highly annotated hematological
specimens for image-based and omic characterization of CHIP; the BWH dermatopathologic tissue repository
will provide annotated FFPE samples for melanoma precursors. These services will also play a key role in
prospective sample acquisition and analysis. Aim 3 will establish a Characterization Unit directed by an
oncologist and pathologist to perform and integrate single-cell genomics, multiplex flow cytometry and high-
plex imaging using two methods reduced to practice within the Center: tissue-based cyclic
immunofluorescence (t-CyCIF) and DNA exchange imaging (DEI). The Characterization Unit will also validate
reagents and associate all primary results with appropriate metadata, protocols and reagent specifications.
Aim 4 will establish a Data Analysis Unit enlisting systems and computational biologists and data scientists to
manage all aspects of data acquisition, interpretation and visualization. This is expected to be the most
technically challenging aspect of the Atlas projects. The Data Analysis Unit will release Phase I/II atlases each
in preliminary and final stages to facilitate collaborative and crowd-sourced approaches to algorithm
development. The resulting human browsable and machine-readable atlases are expected to yield new
scientific discoveries, demonstrate the feasibility and utility of new technologies and help to reduce the
incidence of life-threatening cancers of the skin and blood.
SUMMARY-ABSTRACT
项目成果
期刊论文数量(0)
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