PEBBLE BioFusion | Part 1

Damage, division, and death

What does a damage threshold add to a lineage tree, before we make damage accumulation itself more complicated?

Terminal cells-
Mean terminal damage-
Damage range-
Correlation with O-history-
Cells that died-
Lineage tree: each dot is one cell; colour is damage
O edge: larger inherited shareN edge: smaller inherited sharelow damagehigh damage✕ cell died before dividing
Terminal damage distribution
Present state versus ancestry

Pair challenges

  1. Start with 1. Symmetric. Predict whether O-history should predict terminal damage.
  2. Choose 2. Asymmetric. Increase asymmetry from 0.18 to 0.30. What changes in the tree and scatter plot?
  3. Choose 3. More repair. Does repair change the ancestry pattern, survival, or both?
  4. Choose 4. Lower threshold. Which branches disappear first? How does death make the surviving tree a selected subset of the original tree?
  5. Make one evidence-based claim: “Changing ___ caused ___ in the ___ plot; therefore ___.”
The minimal toy model: a cell repairs a fixed fraction of its old damage, accumulates a fixed amount of new damage plus noise, and then dies if its damage crosses a threshold. Otherwise it divides.
Pt = max(0, (1 - r) Dt + a + εt)
if Pt ≥ T: cell dies before division
DOt+1 = (0.5 + s) Pt,   DNt+1 = (0.5 - s) Pt
Here D is inherited damage, a is new damage per cycle, r is repair, ε is noise, T is the death threshold, and s is partitioning asymmetry. There is no damage feedback and no damage-dependent repair in this first model.