Mendelian disease traces

How to read a prediction: determinate vs SCC ?

PhysioMap predicts the comparative-statics sign — the direction a quantity moves at the new steady state after all feedback has settled, sign(dx*/dθ) — not the naive forward product of edge signs along a path.

Determinate (↑ / ↓). The lesion drives the endophenotype one way regardless of the (unknown) reaction strengths — every numerical model consistent with the sign pattern agrees. PhysioMap commits to ↑ or ↓. These predictions are sound: validated against the real HPO gene→phenotype data, a determinate sign is never wrong.

SCC ? (magnitude-dependent). An SCC (strongly connected component) is a set of variables wired into a feedback loop — each reachable from the others. The largest homeostatic SCC in this map has exactly 213 nodes. When an endophenotype sits inside such a loop, opposing feedback arms fight, and the net steady-state sign depends on how strong each arm is — information a qualitative model does not have. Rather than guess, PhysioMap returns ? and abstains. The trace still shows the forward mechanism (e.g. “forward says ↑”), making explicit that steady state ≠ path propagation — getting pressure-natriuresis and the baroreflex right is exactly why we use comparative statics.

Honest abstention is a feature: PhysioMap reports a sign only when it is forced, so the ↑/↓ calls you do see are trustworthy.