Mouse Tumor Biology Database User Help Reference


MMHCdb Basics

What information can I find in the Mouse Models of Human Cancer (MMHCdb) Database?

  1. The focus of MMHCdb is on in vivo mouse models, including:
    • spontaneous and induced tumors in mice
    • genetically engineered mouse models of cancer
    • diversity panels (e.g., Diversity Outbred, Collaborative Cross, etc.)
    • Patient Derived Xenograft (PDX) models
  2. Information about cancer models includes the spectrum of tumor types observed and the frequency of specific tumor types. We emphasize the effect of genetic background on the cancer characteristics of mouse models. For PDX models, genomics data for engrafted tumors and treatment response data for cohorts of tumor bearing mice are available for most models.
  3. The data about mouse models of human cancer in MMHCdb are acquired from the following sources:
    • the published scientific literature, and
    • the direct submission of model information and pathology images from cancer researchers.
  4. Priority for biocuration activities are determined by the novelty of the mouse model, the quality of the data, and the organ system involved. High priority is given to models associated with the cancers with the highest reported mortality in the United States population.
  5. MMHCdb reports negative as well as positive data. For example, strains of mice that are reported to have a zero frequency of a particular tumor type are included in the database.
  6. Except for PDX models, the mouse model information accessible from MMHCdb is NOT limited to the strains distributed by The Jackson Laboratory. However, if a strain listed in MMHCdb is distributed by The Jackson Laboratory, a link to the data sheet in the JAX Mice database is provided. MMHCdb collaborates with the European Bioinformatics Institute (EBI) to develop and maintain PDX Finder, a global catalog of PDX models which can be accessed at https://www.pdxfinder.org
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How do I cite MMHCdb?

MMHCdb is supported by grant CA89713, entitled "Electronic Access to Mouse Tumor Data", awarded to Carol J. Bult from the National Cancer Institute (NCI) of the National Institutes of Health (NIH).

Please use the following citation when referring to the Mouse Models of Human Cancer Database.

If you wish to cite a specific area of MMHC we suggest a format similar to the following example:

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How can I contribute my data about mouse models of human cancer to MMHCdb?

Submissions of supporting data for new and existing mouse models of human cancer from the research community are welcome. Contact User Support to request a consultation with an MMHCdb Biocuration Scientist about submitting.

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Dynamic Tumor Frequency Grid

The dynamic tumor frequency grid presents the same information as the existing tumor frequency grid, but allows the data to be refined by the user.

Individual strain families and organ groups can be selected to generate a customized grid.

In the resulting grid, individual strains and organs can be selected to further refine the grid's contents. Use the check boxes to select the desired strain and organ rows and columns, then click the 'Generate Grid' button.

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Advanced Search Results

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Model Details

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Strain Details

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Reference Details

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PDX Search Form

PDX model identifier: A unique identifier assigned by the database management system to unambiguously identify a PDX model.

Primary cancer site: The primary cancer site is the anatomical site of the cancer origin. More than one primary site can be selected for a search.

Cancer type tags: Tags are used to group models that share clinical characteristics.

Diagnosis: Cancer diagnoses are standardized using terms from the Disease Ontology (DO). More than one term can be selected for a search.

PDX Dosing studies: PDXs that have been used in dosing studies can be searched by treatment and/or treatment responses. Treatment responses are based on modified RECIST criteria. Read more on dosing study design and interpretation here.

Tumor mutation burden (TMB): Tumor mutation burden is a measurement of the number of mutations carried by tumor cells. TMB is potentially a predictive biomarker to identify tumors that are likely to respond to immunotherapy. In the JAX collection of PDXs, a score of 22 is considered high TMB. Read more about how TMB is calculated here.

Gene fusion: Search for PDX models whose engrafted tumor harbors a gene fusion. Only gene fusions associated drug efficacy or cancer-related evidences are reported. Read more about the methods here.

Gene variants: Search for PDX models whose engrafted human tumors harbor specific gene variants. Gene symbols must be official HGNC symbols. Once a gene symbol is specified, the variants/mutations observed in the PDX collection are displayed. More than one variant/mutation per gene can be selected. Genes that can be searched are restricted to those genes on the JAX Cancer Treatment Profile (CTP) gene panel. Read more about the methods and results here.

Gene expression across PDX models: Displays a graphical summary of expression levels across PDX models for a gene. Only genes on the JAX CTP panel can be searched. Gene symbols must be official HGNC symbols. Read more about gene expression data here.

Gene amplification/deletion across PDX models: Displays a graphical summary of gene expression across PDX models for a gene with the bars representing expression colored according to amplification/deletion status of the gene. Only genes on the JAX CTP panel can be searched. Gene symbols must be official HGNC symbols. Read more about copy number aberration data here.

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PDX Search Results

PDX models matching the search criteria are displayed in a dynamic table.

The results can be sorted by any column. Columns can be resized or hidden.

Click the model ID to go to the model details page to see any additional data.

To send an email requesting additional information on PDX models select models using the check boxes and click the 'Request Details' button.

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PDX Details

Variant, expression and copy number data may not be available for all models.

Variant data

The variant data (point mutations and indels) are analyzed from next-generation sequencing using various capture panels:

The analysis of the sequencing output uses the Xenome tool to remove contaminating mouse sequences before alignment and variant calling.

BWA, GATK, and SnpEff are utilized for alignment (GRCh38 human reference), variant calling and annotation.

The variant results also include clinical annotations using the JAX proprietary clinical knowledge base (CKB).

The high quality variants are further filtered to remove likely false positives, variants with low and modifier impact based on SnpEff annotations, and putative germline variants.

However, all high quality variants that are listed in the JAX CKB database with associated drug efficacy or cancer-related evidences are retained regardless of the filters. The following table describes the fields used in the variant summary data.

Field Description

Model

'T' or 'J' number ID of model

Sample

Alpha-numeric designation (followed by _model id number)

Gene

HGNC nomenclature

Platform

Capture panel used (Truseq-JAX, CTP or Whole Exome)

Chromosome

Chromosome number

Seq Position

Chromosomal position of variant start (in reference sequence)

Ref Allele

Nucleotide(s) present in reference sequence

Alt Allele

Nucleotide(s) present in sample

Consequence

Functional annotation of the variant

Amino Acid Change

Protein sequence change from reference

RS variants

Accession numbers for public databases (dbSNP, COSMIC)

Read Depth

Number of reads at variant site

Allele Frequency

Percentage of variant found as part of total alleles

Transcript ID

RefSeq accession for canonical transcript

Filtered Rationale

Indication of filters which the variant failed.

Germline-Alt_AF_{percent} or PutativeGermline: A variant is predicted to be germline based on public databases and its alternate allele percentage frequency

Passage Num

Passage number of PDX tumor sample assayed

Gene ID

Accession number of gene in Entrez or Ensembl

CKB Evidence

Types of evidence in JAX CKB associated with the variant.

Actionable: Actionable evidence is clinical or preclinical data supporting a connection between a gene variant and a drug response.

The related response type may be sensitive or resistant.

Emerging: Emerging provides evidence for potential development of a gene variant as a future cancer therapy target.

Actionable Cancer Types

Tumor type directly associated with the variant in JAX CKB

Drug Class

Drug classes of treatment approach associated with the variant in JAX CKB

Variant Num Trials

Number of clinical trials directly associated with the variant (The clinical trials associated with the gene can be made available upon request.)

Variant NCT IDs

NCT IDs of clinical trials directly associated with the variant

Expression data

The expression data are analyzed from microarray or RNAseq platforms.

Gene expression of the CTP panel genes is displayed as a chart of percentile rank z-score,

which measures each gene's model-specific expression in comparison with that gene in all models assayed by the same platform.

The mean and standard deviation for z-score calculation is obtained based on a fixed set of PDX samples for each platform.

Other forms of expression values (e.g. z-score, normalized expression) and expression of other genes not listed on the MMHCdb site can be made available upon request.

Genes flagged with hatched bars in gene expression chart

Some genes display a fair amount of heterogeneity in the normal population. This means that some may align poorly to the reference genome. The Genome Reference Consortium "provides multiple representations (alternate loci) for regions that are too complex to be represented by a single path." We have analyzed the data for several samples using both the primary build only and the primary build with the alternate loci. Using the extended reference genome introduces complications in interpreting the gene expression, so we have opted to use only the primary build.

We are flagging the genes where the alternate loci are sufficiently different from primary to caution users that expression of these genes could be artifactually lowered.

Gene Fusion

For gene fusion, the gene symbols upstream and downstream of the fusion are reported and whether the downstream fusion partner is frame-shift or in-frame-shift. Only those with associated drug efficacy or cancer-related evidences are reported to minimize false-positives. Other detected fusions and additional information (e.g. breakpoint coordinates) can be made available upon request.

Copy number

The copy number variation is analyzed from the Affymetrix Human SNP 6.0 array. PennCNV-Affy and ASCAT 2.2 are used to predict allele-specific copy number and ploidy. Gene-level copy number is obtained by intersecting copy number segments with genome coordinates of Ensembl genes. In cases where a segment boundary is contained within a gene's coordinates, the most conservative estimate of copy number is used.

In Gene CNV, the copy number of the CTP panel genes is displayed as a chart of log2(cn raw / sample ploidy). The CNV Plots present the difference from sample ploidy along the chromosomes (orange) and indicate where loss of heterozygosity occurs (blue).

Values for specific genes not listed on the MMHCdb site can be made available upon request.

Tumor mutation burden (TMB) estimation:

TMB was calculated using variants that

TMB was estimated by dividing the number of variants that met the criteria list above by the length (in Mb) of The Jackson Laboratory Cancer Treatment Profile (CTP) targeted gene panel.

We defined high TMB as 22 mutations/Mb, which was calculated based on the TMB distribution of all PDX models analyzed as follows: Q3 (third quartile of TMB) + 1.5 x inter-quartile range of TMB.

Microsatellite Instability (MSI)

The MSIsensor2 algorithm was used to determine MSI status of JAX samples. The samples with MSI-Percentage > 20% are considered MSI-High. This threshold demonstrates good differentiation between MSI-High (MSI-H) and MSI-Stable (MSI-S) samples during MSIsensor2 algorithm development and our internal benchmarking.

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Detected fusion genes are annotated with the clinical information from the JAX CKB database (similar to variant annotation described above), and only those with associated drug efficacy or cancer-related evidences are reported to minimize false-positives.

Other detected fusions and additional information (e.g. breakpoint coordinates) can be made available upon request.


Citing MMHCdb

MMHCdb is supported by grant CA89713 from the National Cancer Institute (NCI).

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