Skip to content

Mutation Frequency

Overview

The Mutation Frequency app within the MMRF Virtual Lab allows users to visualize the most frequently mutated genes and the most common somatic mutations across the selected cohort. It provides insight into the mutation landscape of the cohort, enabling researchers to identify patterns in gene alteration frequency, impact, and survival outcomes.

Access this tool from the Analysis Center by selecting the Mutation Frequency card.

Mutation Frequency Entry Point App

Available Visualizations

The Mutation Frequency tool includes multiple interactive visualizations and tables to explore mutation data:

  • Mutated Genes Histogram
  • Mutation Frequency Survival Plot
  • Genes/Mutations Table
  • Gene Summary Page
  • Mutation Summary Page

Mutation Frequency Overview

Mutated Genes Histogram

This histogram displays the most frequently mutated genes within the active cohort. Each bar represents a gene, with its height corresponding to the percentage of cases affected.

Key Features:

  • Visualize the top mutated genes across the selected cohort.
  • Hover over bars to view the exact number and percentage of affected cases.
  • Download the histogram as an image (SVG or PNG) or as raw data (JSON) using the icons in the top-right corner.
  • Use filters on the left panel to refine results by gene impact, consequence type, or biotype.

Mutated Genes Histogram

Survival Plot for Mutated Genes and Mutations

The survival plot compares overall survival between patients with and without a selected gene mutation or variant. Two Kaplan–Meier curves represent these groups, helping users assess whether a specific mutation impacts survival outcomes.

Key Features:

  • Apply additional filters (e.g., Biotype = IncRNA) to refine which cases are included in the plot.
  • View the Log-Rank Test p-value to assess statistical significance.
  • Download the survival plot as an image (SVG/PNG) or export the data (JSON/TSV).
  • Use the reset button to clear selections and return to default view.

Survival Plot

Genes and Mutations Table

The Genes/Mutations Table lists the most frequently mutated genes or variants, ranked by percent frequency within the active cohort. This table provides additional context, including copy number variation (CNV) data and affected case counts.

Key Features:

  • Toggle between Genes and Mutations view.
  • Filter or search by gene name, mutation type, or genomic position.
  • Click the Cohort toggle to filter the current cohort by the selected gene or mutation.
  • Select Survival to dynamically update the survival plot for that variant.
  • Export the table data as a JSON or TSV file.
  • Create new cohorts based on any gene or mutation using the action buttons in each row.

Genes Table

Gene and Mutation Summary Pages

Users can click on the Gene Symbol in the Genes Table or the DNA Change link in the Mutations Table to open dedicated summary pages for that entity. These pages display additional biological context, clinical impact, and frequency data across MMRF projects.

Gene Summary Page

The Gene Summary page provides detailed information and analytics for a selected gene, including mutation and CNV data across MMRF cohorts.

Gene Summary Section

  • Symbol: Official gene symbol.
  • Name: Full gene name.
  • Synonyms: Known aliases or alternative names.
  • Type: Broad classification (e.g., protein-coding, pseudogene).
  • Location: Chromosome number and coordinates.
  • Strand: Indicates if the gene is on the forward (+) or reverse (−) strand.
  • Description: Summary of gene function and biological relevance.
  • Annotation: Indicates whether the gene is part of the Cancer Gene Census (CGC).

External References

Links are provided to relevant external databases for additional information:
Entrez, UniProt, HGNC, OMIM, Ensembl, and CIViC.

Gene Summary

Cancer Distribution

Displays how frequently the gene is altered (mutations or CNVs) across MMRF studies.

Visuals include:

  • Bar charts showing the number and percentage of affected cases by project.
  • A table summarizing # of cases, percent affected, and unique mutations per project.

Most Frequent Mutations

Lists the top 20 mutations found in the selected gene.

For each mutation, the following fields are displayed: - DNA Change: Chromosome, position, and nucleotide substitution.
- Protein Change: Resulting amino acid change.
- Type: General mutation classification (e.g., missense, nonsense).
- Consequence: The biological effect (e.g., synonymous, noncoding).
- # Affected Cases in Gene: Cases impacted by this mutation in the current dataset.
- Impact: Severity classification (High, Moderate, Low, Modifier).

All data can be exported in TSV format for external analysis.

Mutations Table

Mutation Summary Page

The Mutation Summary page provides detailed information about a single somatic mutation and its functional consequences.

Mutation Summary Section

  • UUID: Unique mutation identifier.
  • DNA Change: Chromosome number, position, and nucleotide change.
  • Type: Mutation classification.
  • Reference Genome Assembly: Genome build reference (e.g., GRCh38).
  • Reference Allele: Nucleotide(s) in the reference sequence.
  • Functional Impact: Severity of the variant’s predicted effect.

External References

Quick links to external mutation databases: dbSNP, COSMIC, and CIViC.

Consequences

A table describes the mutation’s biological impact based on Sequence Ontology terms:

Field Description
Gene Affected gene symbol
AA Change Amino acid substitution and position
Consequence Effect of mutation on coding potential
Coding DNA Change Exact nucleotide change and position
Impact Predicted consequence severity (from VEP, SIFT, PolyPhen)
Transcript Affected transcript ID (linked to Ensembl)

Mutation Summary

Cancer Distribution

Displays how many cases across MMRF projects contain this mutation.
A bar graph and table summarize affected case counts and percentages by project.

Filtering Mutations and Genes

Facet Filters

Frequently used filters available on the left panel include:

  • Biotype: Gene classification (e.g., protein-coding, lincRNA, pseudogene).
  • Is Cancer Gene Census: Filter for known cancer-associated genes (enabled by default).
  • Consequence Type: Biological effect category (missense, frameshift, stop-gained, etc.).
  • Mutation Type: High-level classification (SNV, insertion, deletion, etc.).

Exporting and Downloading

  • Download Visualizations: Save as .svg or .png.
  • Export Data: Tables can be exported in .tsv or .json.
  • Save Subsets: Create new cohorts from within the interface.

© The Multiple Myeloma Research Foundation. All rights reserved.