DLBC Description

Cancer effect size is a metric that quantifies the intensity of natural selection on somatic mutations in cancer cell lineages. The output of CancereffectsizeR primarily includes quantified cancer effect sizes (selection intensities) of somatic variants, i.e., how much each mutation contributes to cancer cell proliferation and survival in a given tumor cohort (it produces site-specific mutation rates). Because of the variants being single-nucleotide variants (SNVs), users will see that the endpoint coordinate on the chromosome is one greater than the start position.

This track displays the Cancer Effect Size values (as "Score") for DLBC (Lymphoid Neoplasm Diffuse Large B-cell Lymphoma). Values have been transformed from the scaled selection coefficients via the transformation f(x) = (10 · log(x)) − 10.

A positive score indicates positive selection, a score of 1 represents neutral selection, and a score of "0" reflects negative selection (not quantified). To transform positive track values back to scaled selection coefficients, use the transformation 10^((y+10)/10), where y is the track value provided.

You can search for specific cancer effect size variants by typing the gene_variant names (e.g., TTN_S4020T, ABCB8_V373G) in the UCSC Genome Browser search box. These names correspond to the mutation identifiers indexed in this track, enabling quick navigation to relevant variants.

Display Conventions and Configuration

The track is presented in bigBed format. The file has the following fields:

• chrom – Reference sequence chromosome or scaffold
• chromStart – Zero-based start position of the variant (SNV)
• chromEnd – End position (exclusive) of the variant (SNV)
• gene_variant – Gene and variant identifier
• Score – Selection intensity value

Methods

The cancer effect size in CancereffectsizeR is calculated by estimating the neutral mutation rate at each variant site using tissue-specific gene mutation rates and mutational signatures, then comparing the observed mutation rate to this neutral rate. The resulting score, called the selection intensity or cancer effect size, reflects the relative proliferative advantage that a mutation confers to cancer cells.

Contact

Please feel free to contact Dr. Jeffrey P. Townsend (jeffrey.townsend@yale.edu) with any questions and/or concerns regarding this track.

References

Mandell JD, Cannataro VL, Townsend JP. Estimation of neutral mutation rates and quantification of somatic variant selection using cancereffectsizeR. Cancer Research. 2023 Feb 15; 83(4):500–505. doi:10.1158/0008-5472.CAN-22-1508