Mutually Exclusive Exon Switch

Identify reciprocal switching between mutually exclusive exons.

Description

When two alternatives exhaust the supplied exon counts, their usage shifts are equal and opposite.

When two alternatives exhaust the supplied exon counts, their usage shifts are equal and opposite. A reciprocal shift is thus an arithmetic consequence of the two-category model.1

Identify reciprocal switching between mutually exclusive exons.

When to use Mutually Exclusive Exon Switch

Use this tool to identify reciprocal switching between mutually exclusive exons.

Prepare the upstream counts, expression values, sequences or record lists requested by this tool. Keep corresponding features in the same order and confirm count units, transformations and caller-selected criteria.

How to use Mutually Exclusive Exon Switch and understand its results

  1. Prepare the upstream counts, expression values, sequences or record lists requested by this tool. Keep corresponding features in the same order and confirm count units, transformations and caller-selected criteria.
  2. Enter controlExonOne, controlExonTwo, treatmentExonOne, treatmentExonTwo, minimumSwitchPoints using the field table and calculation rules, then run the tool.
  3. Read exonOneUsageShift, exonTwoUsageShift, mutuallyExclusiveSwitch. The explanation below defines the units, signs, ordering and any flags or placeholder values.
  4. If the tool reports an input issue, correct the values and run it again. Apply the stated assumptions when interpreting a successfully returned result.
Input fieldMeaningValue type; see rules belowRequirement
controlExonOneControl exon onenumberRequired
controlExonTwoControl exon twonumberRequired
treatmentExonOneTreatment exon onenumberRequired
treatmentExonTwoTreatment exon twonumberRequired
minimumSwitchPointsMinimum switch pointsnumberRequired

Enter four nonnegative counts with positive control/treatment totals and a finite minimum shift criterion. Return both signed percentage-point shifts. The switch flag requires absolute shift at least the criterion and a strictly negative product of the two shifts, excluding a zero shift.

shift1=100[treatmentExon1/treatmentTotal−controlExon1/controlTotal]; shift2=−shift1

Units, indexing, boundary conditions and exceptional cases are defined in the calculation rules above.

Output fieldMeaningValue type
exonOneUsageShiftExon one usage shiftnumber
exonTwoUsageShiftExon two usage shiftnumber
mutuallyExclusiveSwitchMutually exclusive switchboolean
json
{
  "input": {
    "controlExonOne": 80,
    "controlExonTwo": 20,
    "treatmentExonOne": 30,
    "treatmentExonTwo": 70,
    "minimumSwitchPoints": 20
  },
  "output": {
    "exonOneUsageShift": -50,
    "exonTwoUsageShift": 50,
    "mutuallyExclusiveSwitch": true
  }
}

Limitations and assumptions

This does not establish exon mutual exclusivity from alignments or perform significance testing. Additional isoforms, replicate uncertainty and coverage effects are not modeled.

Numeric inputs must be finite. Follow the calculation-specific rules for overflow, underflow and exceptional cases. Missing required fields, extra fields, wrong value types and violations of the calculation rules are input errors. A successfully returned false flag is an evaluated outcome; its meaning is explained above.

Alternative or Complementary methods

Use Exon Skipping Psi: Quantify exon-skipping percent-spliced-in from junction counts. For a complementary task, use Alternative 3prime Splice Shift: Detect alternative 3-prime acceptor site usage shifts.

References

  1. Mutually Exclusive Exon Switch — tool.io

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