Past exam of the systems biology course of the University of Cambridge / 2024 / Paper 4 / Section I / 1.14 / Solution 2026-10-20
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Two useful changes would be:
  • Show patient estimates together with matched, relevant cell-type controls and an independent measurement of modification at prespecified or held-out loci. Display uncertainty and all evaluated loci, or state a selection rule independent of the reported contrast. This separates genuine agreement from selection of high xPore values and from unrelated cell-background effects.
  • Add performance across measured RNA-input levels for the same biological materials, with biological and technical replication, read coverage and failure rates reported. This tests the low-input part of the claim directly rather than inferring it from the heatmap.
A single additional knockout row would not address both independent accuracy and input dependence.
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Past exam of the systems biology course of the University of Cambridge / 2024 / Paper 4 / Section I / 1.5 / Solution 2026-10-20
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Define the evaluation universe first, including which sufficiently covered loci were eligible for both methods. Relative to the reference assay's labels,
(1)
The true positive rate is the fraction of reference-positive loci retained by xPore; the false positive rate is the fraction of reference-negative loci incorrectly retained. The latter is not the fraction of xPore calls that fail validation.
An imperfect reference assay can miss real modifications. “False positive” here therefore means disagreement with that reference, not independently demonstrated absence of a modification. Restricting the universe differently for the two denominators would invalidate the comparison.
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