RESUMO
PDCM Finder (www.cancermodels.org) is a cancer research platform that aggregates clinical, genomic and functional data from patient-derived xenografts, organoids and cell lines. It was launched in April 2022 as a successor of the PDX Finder portal, which focused solely on patient-derived xenograft models. Currently the portal has over 6200 models across 13 cancer types, including rare paediatric models (17%) and models from minority ethnic backgrounds (33%), making it the largest free to consumer and open access resource of this kind. The PDCM Finder standardises, harmonises and integrates the complex and diverse data associated with PDCMs for the cancer community and displays over 90 million data points across a variety of data types (clinical metadata, molecular and treatment-based). PDCM data is FAIR and underpins the generation and testing of new hypotheses in cancer mechanisms and personalised medicine development.
Assuntos
Neoplasias , Humanos , Criança , Neoplasias/genética , Neoplasias/terapia , Organoides , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND: Patient-derived xenografts (PDX) mice models play an important role in preclinical trials and personalized medicine. Sharing data on the models is highly valuable for numerous reasons - ethical, economical, research cross validation etc. The EurOPDX Consortium was established 8 years ago to share such information and avoid duplicating efforts in developing new PDX mice models and unify approaches to support preclinical research. EurOPDX Data Portal is the unified data sharing platform adopted by the Consortium. MAIN BODY: In this paper we describe the main features of the EurOPDX Data Portal ( https://dataportal.europdx.eu/ ), its architecture and possible utilization by researchers who look for PDX mice models for their research. The Portal offers a catalogue of European models accessible on a cooperative basis. The models are searchable by metadata, and a detailed view provides molecular profiles (gene expression, mutation, copy number alteration) and treatment studies. The Portal displays the data in multiple tools (PDX Finder, cBioPortal, and GenomeCruzer in future), which are populated from a common database displaying strictly mutually consistent views. (SHORT) CONCLUSION: EurOPDX Data Portal is an entry point to the EurOPDX Research Infrastructure offering PDX mice models for collaborative research, (meta)data describing their features and deep molecular data analysis according to users' interests.
Assuntos
Neoplasias , Animais , Xenoenxertos , Humanos , Disseminação de Informação , Camundongos , Neoplasias/genética , Medicina de Precisão , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Patient-derived tumor xenograft (PDX) mouse models are a versatile oncology research platform for studying tumor biology and for testing chemotherapeutic approaches tailored to genomic characteristics of individual patients' tumors. PDX models are generated and distributed by a diverse group of academic labs, multi-institution consortia and contract research organizations. The distributed nature of PDX repositories and the use of different metadata standards for describing model characteristics presents a significant challenge to identifying PDX models relevant to specific cancer research questions. The Jackson Laboratory and EMBL-EBI are addressing these challenges by co-developing PDX Finder, a comprehensive open global catalog of PDX models and their associated datasets. Within PDX Finder, model attributes are harmonized and integrated using a previously developed community minimal information standard to support consistent searching across the originating resources. Links to repositories are provided from the PDX Finder search results to facilitate model acquisition and/or collaboration. The PDX Finder resource currently contains information for 1985 PDX models of diverse cancers including those from large resources such as the Patient-Derived Models Repository, PDXNet and EurOPDX. Individuals or organizations that generate and distribute PDXs are invited to increase the 'findability' of their models by participating in the PDX Finder initiative at www.pdxfinder.org.
Assuntos
Biologia Computacional/métodos , Bases de Dados Factuais , Neoplasias/genética , Neoplasias/terapia , Ensaios Antitumorais Modelo de Xenoenxerto , Animais , Regulação Neoplásica da Expressão Gênica , Genômica/métodos , Humanos , Armazenamento e Recuperação da Informação/métodos , Armazenamento e Recuperação da Informação/estatística & dados numéricos , Internet , Metadados/estatística & dados numéricos , CamundongosRESUMO
The Mouse Tumor Biology (MTB; http://tumor.informatics.jax.org) database is a unique online compendium of mouse models for human cancer. MTB provides online access to expertly curated information on diverse mouse models for human cancer and interfaces for searching and visualizing data associated with these models. The information in MTB is designed to facilitate the selection of strains for cancer research and is a platform for mining data on tumor development and patterns of metastases. MTB curators acquire data through manual curation of peer-reviewed scientific literature and from direct submissions by researchers. Data in MTB are also obtained from other bioinformatics resources including PathBase, the Gene Expression Omnibus and ArrayExpress. Recent enhancements to MTB improve the association between mouse models and human genes commonly mutated in a variety of cancers as identified in large-scale cancer genomics studies, provide new interfaces for exploring regions of the mouse genome associated with cancer phenotypes and incorporate data and information related to Patient-Derived Xenograft models of human cancers.
Assuntos
Bases de Dados Genéticas , Modelos Animais de Doenças , Camundongos/genética , Neoplasias Experimentais/genética , Animais , Genômica , Internet , Neoplasias Experimentais/patologia , Locos de Características QuantitativasRESUMO
Many mouse models have been created to study hematopoietic cancer types. There are over thirty hematopoietic tumor types and subtypes, both human and mouse, with various origins, characteristics and clinical prognoses. Determining the specific type of hematopoietic lesion produced in a mouse model and identifying mouse models that correspond to the human subtypes of these lesions has been a continuing challenge for the scientific community. The Mouse Tumor Biology Database (MTB; http://tumor.informatics.jax.org) is designed to facilitate use of mouse models of human cancer by providing detailed histopathologic and molecular information on lymphoma subtypes, including expertly annotated, on line, whole slide scans, and providing a repository for storing information on and querying these data for specific lymphoma models.
Assuntos
Leucemia/patologia , Linfoma/patologia , Neoplasias Experimentais/patologia , Animais , Bases de Dados Factuais , Modelos Animais de Doenças , Humanos , CamundongosRESUMO
In recent years, the scientific community has generated an ever-increasing amount of data from a growing number of animal models of human cancers. Much of these data come from genetically engineered mouse models. Identifying appropriate models for skin cancer and related relevant genetic data sets from an expanding pool of widely disseminated data can be a daunting task. The Mouse Tumor Biology Database (MTB) provides an electronic archive, search and analysis system that can be used to identify dermatological mouse models of cancer, retrieve model-specific data and analyse these data. In this report, we detail MTB's contents and capabilities, together with instructions on how to use MTB to search for skin-related tumor models and associated data.
Assuntos
Bases de Dados Factuais , Neoplasias Cutâneas , Animais , Modelos Animais de Doenças , Humanos , Camundongos , Neoplasias Experimentais/genética , Neoplasias Experimentais/patologia , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologiaRESUMO
The laboratory mouse has served for decades as an informative animal model system for investigating the genetic and genomic basis of cancer in humans. Although thousands of mouse models have been generated, compiling and aggregating relevant data and knowledge about these models is hampered by a general lack of compliance, in the published literature, with nomenclature and annotation standards for genes, alleles, mouse strains and cancer types. The Mouse Models of Human Cancer database (MMHCdb) is an expertly curated, comprehensive knowledgebase of diverse types of mouse models of human cancer, including inbred mouse strains, genetically engineered mouse models, patient-derived xenografts, and mouse genetic diversity panels such as the Collaborative Cross. The MMHCdb is a FAIR-compliant knowledgebase that enforces nomenclature and annotation standards, and supports the completeness and accuracy of searches for mouse models of human cancer and associated data. The resource facilitates the analysis of the impact of genetic background on the incidence and presentation of different tumor types, and aids in the assessment of different mouse strains as models of human cancer biology and treatment response.
Assuntos
Genômica , Neoplasias , Humanos , Camundongos , Animais , Modelos Animais de Doenças , Neoplasias/genética , Alelos , Bases de Dados GenéticasRESUMO
The Mouse Tumor Biology (MTB) database provides access to data about endogenously arising tumors (both spontaneous and induced) in genetically defined mice (inbred, hybrid, mutant and genetically engineered mice). Data include information on the frequency and latency of mouse tumors, pathology reports and images, genomic changes occurring in the tumors, genetic (strain) background and literature or contributor citations. Data are curated from the primary literature or submitted directly from researchers. MTB is accessed via the Mouse Genome Informatics web site (http://www.informatics.jax.org). Integrated searches of MTB are enabled through use of multiple controlled vocabularies and by adherence to standardized nomenclature, when available. Recently MTB has been redesigned and its database infrastructure replaced with a robust relational database management system (RDMS). Web interface improvements include a new advanced query form and enhancements to already existing search capabilities. The Tumor Frequency Grid has been revised to enhance interactivity, providing an overview of reported tumor incidence across mouse strains and an entrée into the database. A new pathology data submission tool allows users to submit, edit and release data to the MTB system.
Assuntos
Bases de Dados Factuais , Modelos Animais de Doenças , Camundongos , Neoplasias Experimentais/genética , Neoplasias Experimentais/patologia , Animais , Gráficos por Computador , Sistemas de Gerenciamento de Base de Dados , Internet , Camundongos/genética , Neoplasias Experimentais/epidemiologia , Interface Usuário-ComputadorRESUMO
Research using laboratory mice has led to fundamental insights into the molecular genetic processes that govern cancer initiation, progression, and treatment response. Although thousands of scientific articles have been published about mouse models of human cancer, collating information and data for a specific model is hampered by the fact that many authors do not adhere to existing annotation standards when describing models. The interpretation of experimental results in mouse models can also be confounded when researchers do not factor in the effect of genetic background on tumor biology. The Mouse Tumor Biology (MTB) database is an expertly curated, comprehensive compendium of mouse models of human cancer. Through the enforcement of nomenclature and related annotation standards, MTB supports aggregation of data about a cancer model from diverse sources and assessment of how genetic background of a mouse strain influences the biological properties of a specific tumor type and model utility. Cancer Res; 77(21); e67-70. ©2017 AACR.
Assuntos
Bases de Dados Genéticas , Neoplasias/genética , Animais , Modelos Animais de Doenças , Humanos , Internet , Camundongos , Neoplasias/patologiaRESUMO
Patient-derived tumor xenograft (PDX) mouse models have emerged as an important oncology research platform to study tumor evolution, mechanisms of drug response and resistance, and tailoring chemotherapeutic approaches for individual patients. The lack of robust standards for reporting on PDX models has hampered the ability of researchers to find relevant PDX models and associated data. Here we present the PDX models minimal information standard (PDX-MI) for reporting on the generation, quality assurance, and use of PDX models. PDX-MI defines the minimal information for describing the clinical attributes of a patient's tumor, the processes of implantation and passaging of tumors in a host mouse strain, quality assurance methods, and the use of PDX models in cancer research. Adherence to PDX-MI standards will facilitate accurate search results for oncology models and their associated data across distributed repository databases and promote reproducibility in research studies using these models. Cancer Res; 77(21); e62-66. ©2017 AACR.
Assuntos
Neoplasias , Ensaios Antitumorais Modelo de Xenoenxerto/estatística & dados numéricos , Animais , Bases de Dados como Assunto , Modelos Animais de Doenças , Humanos , Camundongos , Neoplasias/tratamento farmacológico , Neoplasias/genética , PacientesRESUMO
Developing genetic mouse models for cancer research has been recognized as an "exceptional opportunity" by the National Cancer Institute. The establishment of bioinformatics resources to facilitate access to published and unpublished data on the genetics and pathology of cancer in different strains of the laboratory mouse is critical to developing and using mouse models of human disease. In this article, we review the Mouse Tumor Biology Database (MTB), a public resource for information on cancer genetics, epidemiology, and pathology in genetically defined mice. We outline current content, data acquisition strategies, and query mechanisms for MTB. MTB is accessible on-line at http://tumor.informatics.jax.org.
Assuntos
Biologia Computacional , Bases de Dados como Assunto , Camundongos/genética , Neoplasias/genética , Doenças dos Roedores/genética , Animais , Neoplasias/patologia , Doenças dos Roedores/patologiaRESUMO
The laboratory mouse has long been an important tool in the study of the biology and genetics of human cancer. With the advent of genetic engineering techniques, DNA microarray analyses, tissue arrays and other large-scale, high-throughput data generating methods, the amount of data available for mouse models of cancer is growing exponentially. Tools to integrate, locate and visualize these data are crucial to aid researchers in their investigations. The Mouse Tumor Biology database (http://tumor.informatics.jax.org) seeks to address that need.
Assuntos
Bases de Dados como Assunto , Modelos Animais de Doenças , Neoplasias Experimentais , Animais , Genes p16 , Humanos , Camundongos , Neoplasias Experimentais/genética , Neoplasias Experimentais/patologia , Locos de Características QuantitativasRESUMO
Histology and immunohistochemistry are important tools in the study of human diseases and their respective animal models. The study of mouse models has been hampered by the absence of a large set of mouse-specific antibodies adapted to paraffin-embedded tissues. A total of 196 antibodies were tested on paraffin-embedded mouse tissues preserved in five different fixatives (Fekete's acid-alcohol-formalin, 10% neutral buffered formalin, 4% paraformaldehyde, IHC Zinc Fixative, and Bouin's fixative). The antibodies were targeted to proteins of the cytoplasm (n = 100), plasma membrane (n = 48), nucleus (n = 36), extracellular compartment (n = 5), cytoplasm/cell membrane (n = 4), and viral proteins (n = 3). A total of 83 antibodies provided an adequate signal to noise ratio. Of these, adequate labeling required heat-mediated epitope retrieval or enzymatic digestion for 32 and 8 antibodies, respectively. Epitope recognition was best for tissues fixed with Fekete's acid-alcohol-formalin. However, some proteins could be detected only in IHC Zinc Fixative, confirming that there is no single fixative suitable for the preservation of all epitopes. Four of 13 antibodies that failed to label their cellular targets on tissue sections successfully labeled whole-mount tissues, indicating that tissue processing plays an important role in epitope degradation. Regularly updated information on immunohistochemistry of normal and neoplastic mouse tissues is accessible online at (http://tumor.informatics.jax.org); links to antibody suppliers' web sites are provided.