File S1 - Genomic Instability and Radiation Risk in Molecular Pathways to Colon Cancer

Contains the following files: Table S1. Identifiable baseline parameters in the deterministic and stochastic versions of the two path model with MSI and CIN paths (Figure 1), biological parameters N, νI, αI and γI are set equal in both pathways. Table S2. MLE, SE from a parabolic approximation around the minimum of the likelihood function, and ΔCILP from the actual likelihood profile in the standard σ range for the identifiable parameters of model M1 (Figure S1) with relation to biological parameters, superscript m,f indicates sex-dependence, radiation-response parameters rm,f on dose D are given for lifelong radiation effect on clonal expansion, one initial mutation rate νI increases exponentially with birth year b = 1945.6 – e, the baseline version of model M1 is mathematically equivalent to the three stage model by Meza et al. [1]. Table S3. MLE and SE from a parabolic approximation around the minimum of the likelihood function for the identifiable parameters of model M2 (Figure S2) with relation to biological parameters, superscript m,f indicates sex-dependence, radiation-response parameters r on dose D given for direct radiation effect on mutation rate λ1 with exposure duration of 1 week, mutation rates ν0a, λ0 and ν0b increase exponentially with birth year b = 1945.6 – e, ΔCILP from the actual likelihood profile in the standard σ range could not be computed by MINUIT, the baseline version of M2 is inspired by Nowak et al. [2] and derived from Little and Li [3] (their Figure 2). Table S4. MLE, SE from a parabolic approximation around the minimum of the likelihood function, and ΔCILP from the actual likelihood profile in the standard σ range for the identifiable parameters of model M3 (Figure S3) with relation to biological parameters, deterministic MSI model without dependence on δMSI, superscript m,f indicates sex-dependence, radiation-response parameters rI and rmCIN on dose D are given for an exposure duration of 1 week, one initial mutation rate νI,CIN increases exponentially with birth year b = 1945.6 – e (age at exposure). Figure S1. Parametrisation of model M1 with lifelong radiation action (jagged bolt) on cell inactivation β (TSG: tumor suppressor gene), one initial mutation rate νI increases exponentially with birth year b. Figure S2. Parametrisation of model M2 with radiation action (jagged bolt) on mutation rate λ1, mutation rates ν0a, λ0 and ν0b increase exponentially with birth year b. Figure S3. Parametrisation of model M3 with deterministic MSI path (no dependence on δMSI) and stochastic CIN path, radiation action (jagged bolt) on second initial mutation rate νI equal in MSI and CIN paths and on cell inactivation βCIN for men only, one initial mutation rate νI,CIN increases exponentially with birth year b.
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