Fig 1.
Dynamics of mutant cells and incidence of PNH derived from in silico studies.
A. The probability of clinical PNH occurring in an individual between the ages of 1–100 years. Blue: patients with one active clone. Red: patients with 2 active clones. Yellow: patients where 3 or more active clones occurred. B. Expected incidence of clinical PNH in the US population, found by folding the Markov chain probabilities for ages 1–100 with population data from the 2010 US census. Same color codes as in A. C. The distribution of all individuals with a mutant clone in the 2010 US census population over the ages 1–100 and clone sizes 1%-100%.
Fig 2.
A. Likelihood of existence of clones over time. As a test of accuracy, the probabilities for the existence of the primary and secondary clones were also calculated analytically from a cumulative negative binomial distribution. Although the probability of harboring a clone is certainly non-negligible for most age groups, it is clear that the probability of diagnosis is many orders of magnitude smaller. B. The probability of obtaining a first or second clone in a given year as well as the probability of reaching the diagnosis threshold (20% of the HSC pool) folded with the 2010 US population distribution. The prevalence of every curve has been normalized to 1, so that these results may be interpreted as the age distribution of the clone and diagnosis arrival times. (M.C.: Markov Chain simulations; an.: Analytical calculations.)
Fig 3.
A. The size probability distribution for an established clone multiple years after diagnosis (20%). Being a one hump function, the distribution is asymmetric, stretching further to the right (larger sizes, see main text for details). B. Probabilities for an established clone to recede or vanish after diagnosis (20%) over time.
Fig 4.
The state space and allowed transitions.
Each history describes a possible evolution where either 0 (left), 1 (middle) or 2 (right) mutations were acquired by healthy cells. Whenever a mutation occurs the system jumps to the next panel on the right (to the next history), until the final history is reached where mutations are no longer allowed. The dark blue arrows represent incoming transitions from nearest neighbor states in the same history, while the red arrows represent transitions from states in the previous history. Note that every state also has a transition onto itself, which has been left out for readability.