Tumor Normal Copy Ratio

Interpret log2 tumor/normal ratios with an explicit normal-cell admixture and baseline ploidy model.

Description

Tumor/normal copy ratios mix tumor cells with normal cells.

Tumor/normal copy ratios mix tumor cells with normal cells. Purity determines how strongly observed ratios differ from the tumor copy-number state.1

Interpret log2 tumor/normal ratios with an explicit normal-cell admixture and baseline ploidy model.

When to use Tumor Normal Copy Ratio

Use this for the following task: Interpret log2 tumor/normal ratios with an explicit normal-cell admixture and baseline ploidy model.

Prepare the caller-filtered sequences, counts, coordinates or annotations requested below. Keep identifiers and paired lists aligned on the same reference.

How to use Tumor Normal Copy Ratio and understand its results

  1. Prepare the caller-filtered sequences, counts, coordinates or annotations requested below. Keep identifiers and paired lists aligned on the same reference.
  2. Enter log2Ratios, normalPloidy, purityFraction using the field table, then run the tool.
  3. Read observedCopyRatios, tumorCopyNumbers. Interpret flags, units, ordering and placeholder values using the rules below.
  4. Review any reported issue or failed check, correct the supplied values when appropriate, and verify the result in its intended context.
Input fieldMeaningValue type and boundsRequirement
log2RatiosLog2 sample-to-normal ratios in the simple admixture model R = purity * tumorCopies / normalPloidy + (1 - purity).list of number; minimum entries 0; maximum entries 100000; each entry: numberRequired
normalPloidyNormal ploidynumber; greater than 0Required
purityFractionPurity fractionnumber; greater than 0; maximum 1Required

Require a positive baseline ploidy and purity in (0,1]. Transform each log ratio and invert the admixture model, using stable near-zero calculations. Reject incompatible negative copy numbers or nonfinite results.2

ratio = 2^log2Ratio; tumorCopies = normalPloidy[1 + (ratio−1)/purity]

This summarizes the declared operation. Units, indexing, inclusivity and exceptional cases are explained in the surrounding text.

Output fieldMeaningValue type
observedCopyRatiosObserved copy ratioslist of number
tumorCopyNumbersTumor copy numberslist of number
json
{
  "input": {
    "log2Ratios": [
      -1,
      0,
      1
    ],
    "normalPloidy": 2,
    "purityFraction": 1
  },
  "output": {
    "observedCopyRatios": [
      0.5,
      1,
      2
    ],
    "tumorCopyNumbers": [
      1,
      2,
      4
    ]
  }
}

Limitations and assumptions

The inferred copy numbers are continuous model values. Heterogeneity, subclonality and baseline normalization must be assessed separately.

The tool operates on supplied local data; alignment, filtering and annotation must already be appropriate for the stated calculation. Malformed requests produce input errors. A successfully evaluated request can still contain false flags, empty result lists or a result outside the supplied threshold; those outcomes have the meanings stated above.

Alternative or Complementary methods

Choose Purity Ploidy Grid Fit for this operation: Choose the minimum-residual cell from an externally fitted purity-by-ploidy grid. For a complementary task, use Loh Segments for this operation: Merge contiguous segments meeting a supplied minor-allele copy-number LOH criterion.

Further background: Background specification: Tumor Normal Copy Ratio.

References

  1. Background specification: Tumor Normal Copy Ratio — CNVkit

  2. Tumor Normal Copy Ratio — tool.io

Similar or alternative tools

  • Purity Ploidy Grid Fit

    Choose the minimum-residual cell from an externally fitted purity-by-ploidy grid.

  • Loh Segments

    Merge contiguous segments meeting a supplied minor-allele copy-number LOH criterion.

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