## Problem 243 — rank:311

**Title:** Unexplained mutational signatures

**Added binding assumptions (LaTeX):**

```latex
Treat mixture components up to permutations and other nonunique nonnegative factorizations. Mutation counts require calibrated opportunity and detection offsets, or a matched opportunity profile across samples, before profile differences are attributed to processes. The class-specific constraints, not an arbitrary component name, carry causal assignment information. Calibrate any likelihood-compatible region before giving it frequentist coverage semantics.
```

**Direct edits:** 0. **Fresh external checks:** None; supplied sources retained as provenance.