Cancer Biology Data Curation at the Mouse Tumor Biology Database (MTB)

Many advances in the field of cancer biology have been made using mouse models of human cancer. The Mouse Tumor Biology (MTB, "http://tumor.informatics.jax.org":http://tumor.informatics.jax.org) database provides web-based access to data on spontaneous and induced tumors from genetically defined mice (inbred, hybrid, mutant, and genetically engineered strains of mice). These data include standardized tumor names and classifications, pathology reports and images, mouse genetics, genomic and cytogenetic changes occurring in the tumor, strain names, tumor frequency and latency, and literature citations.

Although primary source for the data represented in MTB is peer-reviewed scientific literature an increasing amount of data is derived from disparate sources. MTB includes annotated histopathology images and cytogenetic assay images for mouse tumors where these data are available from The Jackson Laboratory’s mouse colonies and from outside contributors. MTB encourages direct submission of mouse tumor data and images from the cancer research community and provides investigators with a web-accessible tool for image submission and annotation. 

Integrated searches of the data in MTB are facilitated by the use of several controlled vocabularies and by adherence to standard nomenclature. MTB also provides links to other related online resources such as the Mouse Genome Database, Mouse Phenome Database, the Biology of the Mammary Gland Web Site, Festing's Listing of Inbred Strains of Mice, the JAX® Mice Web Site, and the Mouse Models of Human Cancers Consortium's Mouse Repository. 

MTB provides access to data on mouse models of cancer via the internet and has been designed to facilitate the selection of experimental models for cancer research, the evaluation of mouse genetic models of human cancer, the review of patterns of mutations in specific cancers, and the identification of genes that are commonly mutated across a spectrum of cancers.

MTB is supported by NCI grant CA089713

Chandra X-ray observations of Young Clusters II. Orion Flanking Fields Data

We present results of Chandra observations of two flanking fields (FF) in Orion, outside the Orion Nebula Cluster (ONC). The observations were taken with the ACIS-I camera with an exposure time of about 48 ks each field. We present a catalog of 417 sources, which includes X-ray luminosity, optical and infrared photometry and X-ray variability information. We have found 91 variable sources, 33 of which have a flare-like light curve, and 11 of which have a pattern of a steady increase or decrease over a 10 hour period. The optical and infrared photometry for the stars identified as X-ray sources are consistent with most of these objects being pre-main sequence stars with ages younger than 10 Myr. We present evidence for an age difference among the X-ray selected samples of NGC 2264, Orion FF, and ONC, with NGC 2264 being the oldest, and ONC being the youngest.Comment: AJ in press, 32 pages, 13 figures in total, 5 figures available at http://spider.ipac.caltech.edu/staff/solange/ramirez07_figs.p

Magnetic flaring in the pre-main sequence Sun and implications for the early solar system

To address the role of energetic processes in the solar nebula, we provide a detailed characterization of magnetic flaring in stellar analogs of the pre-main sequence Sun based on 23 hours observations of 43 analogs of the young Sun in the Orion Nebula Cluster obtained with the Chandra X-ray Observatory. We find the X-ray luminosities are strongly elevated over main sequence levels with average = 30.3 erg/s and = -3.9 (0.5-8 keV), and dozens of flares are present. Analogs of the <= 1 My old pre-main sequence Sun exhibit X-ray flares 10^{1.5} times more powerful and 10^{2.5} times more frequent than the most powerful flares seen on the contemporary Sun. Extrapolating the solar relationship between X-ray luminosity and proton fluence, we infer that the young Sun exhibited a 10^5-fold enhancement in energetic protons compared to contemporary levels. Unless the flare geometries are unfavorable, this inferred proton flux on the disk is sufficient to produce the observed meteoritic abundances of several important short-lived radioactive isotopes. Our study thus strengthens the astronomical foundation for local proton spallation models of isotopic anomalies in carbonaceous chondritic meteorites. The radiation, particles and shocks produced by the magnetic reconnection flares seen with Chandra may also have flash melted meteoritic chondrules and produced excess 21-Ne seen in meteoritic grains.Comment: 36 pages, 3 figures. Accepted for publication in the Astrophysical Journa

MouseMine: a new data warehouse for MGI.

MouseMine ( www.mousemine.org ) is a new data warehouse for accessing mouse data from Mouse Genome Informatics (MGI). Based on the InterMine software framework, MouseMine supports powerful query, reporting, and analysis capabilities, the ability to save and combine results from different queries, easy integration into larger workflows, and a comprehensive Web Services layer. Through MouseMine, users can access a significant portion of MGI data in new and useful ways. Importantly, MouseMine is also a member of a growing community of online data resources based on InterMine, including those established by other model organism databases. Adopting common interfaces and collaborating on data representation standards are critical to fostering cross-species data analysis. This paper presents a general introduction to MouseMine, presents examples of its use, and discusses the potential for further integration into the MGI interface. Mamm Genome 2015 Aug; 26(7-8):325-30

The Mouse Tumor Biology Database: A Comprehensive Resource for Mouse Models of Human Cancer.

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

The Mouse Models of Human Cancer database (MMHCdb)

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

Finding mouse models of human lymphomas and leukemia\u27s using the Jackson laboratory mouse tumor biology database.

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. Exp Mol Pathol 2015 Dec; 99(3):533-36

In vivo activity of the dual SYK/FLT3 inhibitor TAK-659 against pediatric acute lymphoblastic leukemia xenografts.

BACKGROUND: While children with acute lymphoblastic leukemia (ALL) experience close to a 90% likelihood of cure, the outcome for certain high-risk pediatric ALL subtypes remains dismal. Spleen tyrosine kinase (SYK) is a prominent cytosolic nonreceptor tyrosine kinase in pediatric B-lineage ALL (B-ALL). Activating mutations or overexpression of Fms-related receptor tyrosine kinase 3 (FLT3) are associated with poor outcome in hematological malignancies. TAK-659 (mivavotinib) is a dual SYK/FLT3 reversible inhibitor, which has been clinically evaluated in several other hematological malignancies. Here, we investigate the in vivo efficacy of TAK-659 against pediatric ALL patient-derived xenografts (PDXs). METHODS: SYK and FLT3 mRNA expression was quantified by RNA-seq. PDX engraftment and drug responses in NSG mice were evaluated by enumerating the proportion of human CD45 RESULTS: FLT3 and SYK mRNA expression was significantly higher in B-lineage compared with T-lineage PDXs. TAK-659 was well tolerated and significantly prolonged the time to event in six out of eight PDXs tested. However, only one PDX achieved an objective response. The minimum mean %huCD45 CONCLUSIONS: TAK-659 exhibited low to moderate single-agent in vivo activity against pediatric ALL PDXs representative of diverse subtypes