SUPPLEMENTARY MATERIALS
AUTOMATED DICENTRIC ABERRATION SCORING FOR TRIAGE DOSE ASSESSMENT:
60CO GAMMA RAYS DOSE-RESPONSE AT DIFFERENT DOSE RATES
Uma Subramanian,1 Brett O’Brien,1 Maureen McNamara,1 Lyudmila Romanyukha,1 David L. Bolduc,1 Cara Olsen,2 and William. F. Blakely1
2nd Revision: 11 Feb 2020
1Scientific Research Department, Armed Forces Radiobiology Research Institute (AFRRI), Uniformed Services University of the Health Sciences (USUHS), Bethesda, Maryland 20889-5648 USA
2 Preventive Medicine and Biostatistics (PMB) Department, Uniformed Services University of the Health Sciences (USUHS), Bethesda, Maryland 20814-4799 USA
For correspondence contact Dr. WF Blakely, Scientific Research Department, Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, 4555 South Palmer Road, Bldg. 42, Bethesda, Maryland 20889-5648, USA, Voice:
(301) 295-0484, Fax: (301) 295-1863 or email at [email protected]
Supplementary Materials
Supplementary Table 1. Poisson over-dispersion tests (u, D, L), zero-inflation Poisson (ZIP) tests and Bayesian test (ZIP vs Poisson) on the dicentric chromosome distribution at three dose rates.
Dose rate (Gy/min) Dose (Gy) Dispersion index
Over-dispersion tests
Significant and over-dispersed?
ZIP tests
Zero-inflated?
Bayesian test
u-test u (p- value)
D (p-value)
L
(p-value) Z index Z (p-value)
CR (p-value)
Bayes factor (2logBF)
Evidence strength
0.10
0 1.003 0.137 0.446 0.541 0.541 No 0.002 0.443 0.541 No -0.779 NEG; Su POIS
0.10 1.012 0.541 0.294 0.335 0.334 No 0.003 0.398 0.445 No -1.741 NEG; Su POIS
0.25 1.019 0.714 0.238 0.281 0.257 No 0.011 0.210 0.256 No -0.708 NEG; Su POIS
0.50 1.003 0.084 0.467 0.561 0.561 No 0.002 0.463 0.561 No -0.867 NEG; Su POIS
0.75 1.012 0.541 0.2944 0.3353 0.3343 No 0.003 0.3985 0.4451 No -4.7411 NEG; Su POIS
1.00 1.012 0.382 0.351 0.398 0.363 No 0.008 0.315 0.362 No -1.345 NEG; Su POIS
2.00 1.020 0.532 0.297 0.326 0.307 No 0.010 0.301 0.329 No -2.262 NEG; Su POIS
3.00 1.028 1.200 0.115 0.125 0.102 No 0.015 0.102 -3.96x1023 No -1.978 NEG; Su POIS
4.00 1.034 0.906 0.182 0.199 0.129 No 0.026 0.098 0.108 No -1.639 NEG; Su POIS
5.00 1.069 1.502 0.067 0.078 0.064 No 0.039 0.063 0.070 No -1.307 NEG; Su POIS
0.60 0 1.003 0.137 0.446 0.541 0.541 No 0.002 0.443 0.541 No -0.779 NEG; Su POIS
0.10 1.059 2.250 0.012 0.028 0.025 Yes 0.027 0.021 0.040 Yes 2.160 POS; Su ZIP
0.25 1.028 0.996 0.160 0.203 0.176 No 0.016 0.132 0.172 No -0.118 NEG; Su POIS
0.50 0.971 -
0.896 0.185 0.218 0.826 No -0.013 0.208 0.259 No -3.745 NEG; Su POIS
0.75 1.047 1.717 0.043 0.068 0.063 No 0.021 0.061 0.089 No 0.749 WP; Su ZIP
1.00 1.018 0.514 0.304 0.353 0.352 No 0.004 0.421 0.474 No -1.647 NEG; Su POIS
2.00 1.068 1.629 0.052 0.072 0.095 No 0.023 0.137 0.163 No -0.817 NEG; Su POIS
3.00 0.945 -
0.265 0.114 0.122 0.897 No -0.026 0.138 0.174 No -4.226 NEG; Su POIS
4.00 1.050 0.742 0.229 0.249 0.222 No 0.028 0.220 0.246 No -1.877 NEG; Su POIS
5.00 1.208 2.358 0.009 0.019 0.015 No 0.100 0.017 0.022 No 1.826 WP; Su ZIP
1.00
0 1.003 0.13
7 0.446 0.541 0.541 No 0.002 0.443 0.541 No -0.779 NEG; Su POIS
0.14 1.035 1.49
3 0.068 0.128 0.122 No 0.018 0.063 0.122 No 1.326 WP; Su ZIP
0.25 0.983 -
0.595 0.276 0.700 1.000 No -0.009 0.272 0.700 No -0.476 NEG, Su POIS
0.50 1.097 3.749 1x104 0.001 0.010 Yes 0.030 0.011 0.030 Yes 3.050 POS; Su ZIP
0.75 1.046 1.358 0.087 0.145 0.132 No 0.025 0.076 0.130 No 1.027 WP; Su ZIP
1.00 1.042 1.428 0.077 0.117 0.097 No 0.023 0.061 0.195 No 0.987 WP; Su ZIP
2.00 0.997 -
0.091 0.464 0.503 0.572 No -0.004 0.404 0.0452 No -3.844 NEG; Su POIS
3.00 1.056 2.203 0.014 0.019 0.043 Yes 0.020 0.068 -1.70x1015 No -1.666 NEG: Su POIS
4.00 1.062 1.352 0.088 0.105 0.100 No 0.030 0.120 0.128 No -2.443 NEG; Su POIS
5.00 1.027 0.666 0.253 0.263 0.227 No 0.018 0.220 0.229 No -4.397 NEG; Su POIS
Analysis of over-dispersed or zero-inflated Poisson distributions were performed using a Shiny R Studio application, GOF Poisson, as described by Fernandez- Fontelo et al. (2018) and Higueras et al. (2018). Data was significant and over-dispersed if p < 0.05 for u, D and L-test, and zero-inflated if p < 0.05 for ZIP and CR- test. Tests were only carried out for data sets with more than 2 dicentrics. D = Dispersion index, Z = Zero-inflation index, Su = Supports, WP = Weak positive, POS = Positive, NEG = Negative, VS = Very strong, POIS = Poisson, ZIP = Zero-inflated Poisson.
Supplementary Table 2A. Linear quadratic fit coefficients for dicentrics per cell dose-response at three 60Co gamma rays dose rates using Dose Estimate software.
Coefficients of linear-quadratic fit
(aberrations/cell = aD2 + bD + c, where D=Dose (Gy) Goodness of Fit Z tests
Dose rate (Gy/min)
a SE b SE c SE
Correlation Coefficient, r Weighted Chi Squared
df p-value c
(p-value) a
(p-value) b
(p-value)
0.10 0.012 0.005 0.0390 0.017 0.046 0.007 0.9952 54.6500 7 - 0.0002 0.0531 0.0398
0.60 0.006 0.010 0.053 0.033 0.053 0.013 0.9675 145.800 7 - 0.0042 0.1550 0.5942
1.00 0.030 0.003 0.016 0.011 0.028 0.004 0.9992 28.1600 7 0.0002 0.0002 0.1802 0.0000
Supplementary Table 2B. Linear quadratic fit coefficients for dicentrics per cell dose- response at three 60Co gamma rays dose rates determined using CABAS software.
Dose rate (Gy/min)
Coefficients of linear-quadratic fit
(aberrations/cell = aD2 + bD + c, where D=Dose (Gy)
a b c
0.10 0.0116 0.0390 0.0462
0.60 0.0016 0.0695 0.0514
1.00 0.0296 0.0157 0.0281
Supplementary Table 3. Blind tests dose rate, dicentric chromosome distribution, total number of dicentrics, dicentrics per cell mean and standard error, and variance.
Dose rate (Gy/min )
Blind sampl e ID
Cells score d
Dicentrics distribution
Tota l Dic
Dic per cell
0 1 2 3 4 >4 Mean SE Variance
0.10 X 1289 121
2 71 6 0 0 0 83 0.064 0.007 0.070
Y 615 453 139 20 2 1 0 189 0.307 0.022 0.318
0.60 X 1297 117
3 122 2 0 0 0 126 0.091 0.014 0.091
Y 394 281 87 21 4 1 0 145 0.368 0.047 0.431
1.00 X 3809 368
0 127 2 0 0 0 131 0.034 0.003 0.034
Y 1668 988 513 130 32 5 0 889 0.533 0.018 0.556
Supplementary Table 4. Blind tests Poisson over-dispersion tests (u, D, L), zero-inflation Poisson (ZIP) tests and Bayesian test (ZIP vs Poisson) on the dicentric chromosome distribution at three dose rates.
Dose rate (Gy/min) Blind test ID Dispersion index
Over-dispersion tests
Significant and over-dispersed? ZIP tests
Zero-inflated?
Bayesian test
u-test u
(p-value) D
(p-value) L
(p-value) Z index Z
(p-value) CR
(p-value) Bayes factor
(2logBF) Evidence strength
0.10 X 1.081 2.069 0.019 0.053 0.040 Yes 0.043 0.015 0.041 Yes 2.789 POS; Su ZIP
Y 1.033 0.580 0.281 0.300 0.370 No 0.005 0.432 0.462 No -2.963 NEG; Su POIS
0.60 X 0.935 -1.653 0.049 0.056 0.986 No -0.034 0.043 0.056 No -3.554 NEG; Su POIS
Y 1.173 2.432 0.008 0.019 0.014 Yes 0.082 0.015 0.020 Yes 2.351 POS; Su ZIP
1.00 X 0.996 -0.158 0.437 0.616 0.655 No -0.002 0.438 0.619 No -1.267 NEG; Su POIS
Y 1.044 1.259 0.104 0.114 0.133 No 0.017 0.179 0.188 No -3.471 NEG; Su POIS
Supplementary Table 5A. Blind tests at three dose rates dose predictions using Dose Estimate software.
Dose rate (Gy/min) Blind sample ID Actual dose (Gy) Predicted dose (Gy)
95% Confidence Limits*
Accuracy, % Predicted dose within 0.5 Gy of actual dose
Lower Upper
0.1 0
X 0.
6 0.42 ± 0.796 0.13 0.71 69 Ye
s
Y 3.
3 3.35 ± 1.098 2.98 3.74 102 Ye
s 0.6
0
X 0.
8 0.76 ± 8.656 0 17.73 95 Ye
s
Y 4.
3 4.13 ± 10.11 0 23.98 96 Ye
s 1.0
0
X 0.
4 0.27 ± 0.182 0 0.63 68 Ye
s
Y 3.
7 3.87 ± 0.210 3.46 4.28 105 Ye
s
*Confidence limits reported are based on the combined Poisson and calibration curve errors.
Supplementary Table 5B. Blind tests at three dose rates dose predictions using CABAS.
Dose rate (Gy/min) Blind sample ID Actual dose (Gy) Predicted dose (Gy) 95% Confidence Limits*
Accuracy, % Predicted dose within 0.5 Gy of actual dose
Lower Upper
0.10 X 0.6 0.415 0.126 0.711 69 Yes
Y 3.3 3.350 2.974 3.737 102 Yes
0.60 X 0.8 0.648 0.420 0.905 81 Yes
Y 4.3 4.148 3.447 4.918 96 Yes
1.00 X 0.4 0.267 0.039 0.442 67 Yes
Y 3.7 3.868 3.620 4.123 105 Yes
*Confidence limits reported are based on the calibration curve errors using CABAS.