The role of noise and positive feedback in the onset of autosomal dominant diseases

BMC Systems Biology

Table 2 Sensitivity of feedback loop to changes in stochasticity parameters

Trial	Expression level	Noise stdev	Time scale (days)	Penetrance	Mean onset
1^b	50%	0.2	2	0.31	2.1/5.9
2	50%	0.5	2	0.94	22.1/20.4
3	50%	1.0	2	1.0	12.5/10.6
4	50%	0.2	5	0.91	21.9/21.8
5^c	52.5%	0.5	2	0.20	6.1/18.7
6	52.5%	1.0	2	0.95	17.8/15.9
7^d	52.5%	0.5	5	0.54	7.5/13.0
8	52.5%	1.0	5	1.0	22.0/18.5
9	55%	0.5	2	0.0	--
10	55%	0.5	5	0.0	--
11^e	55%	1.0	2	0.34	8.8/19.2
12	55%	1.0	5	1.0	2.7/0.1
13^f	60%	1.0	5	0.0	--

Sensitivity of feedback loop 2.a to changes in stochasticity is illustrated here using 100-trial simulations. Expression level is such that 50% is at the critical level: slightly lower expression, with no noise, allows disease to deterministically occur all the time. 100 simulations for each set of conditions were run to compute a penetrance value. When no noise is present, the system is deterministic and no disease occurs as long as the base expression level is 50% or higher. When expression is 60% or higher, no disease occurs even with the highest level of random variation used in this study.

ISSN: 1752-0509