[Simulation question]: Step-By-Step Vs DBSCAN direct DNA damages do not match

[ShahinGHD]

Simulation question

Hi everyone,
I am using both DBSCAN and Step-by-step methods in the same file to see if "Direct" DNA damages are the same for the radionuclide Ac-225.

I previously tested for Lu-77 and Tb-161.
By setting the parameter "u:Sc/DBSCAN/SampleHitsWithProbability = 0.5"
I get good agreement between two methods.
Since the DNA geometry is not important for the DBSCAN method, I set the value to 0.5 assuming that the volume occupied by the DNA plasmid is ~ 50% in the cylindrical shape envelope that is around it. This works for Lu and Tb for both SSB and (DSB+Complex DSB), and the two methods are in agreement within ~7%.

For Ac-225 putting it to 0.5 gives me good total DSB results compared to the step-by-step, but single-strand breaks are overestimated by a factor of 2.

My question is:

Is this correct that for this geometry I set this probability value to 0.5?
I got this value by subtracting the volumes of the cylinder and 100 base pairs based on the dimensions mentioned in the manual.

I attached my input file. Can you please take a look to see if there are any mistakes in it?
I appreciate your time and answer.

Kind Regards,
Shahin

b:Ge/QuitIfOverlapDetected="T"


### # GEOMETRY


#World volume
d:Ge/World/HLX = 20 nm
d:Ge/World/HLY = 20 nm
d:Ge/World/HLZ = 20 nm
s:Ge/World/Material="G4_WATER"


#Circular DNA plasmid
s:Ge/MyDNA/Type=             "tscircularplasmid"
s:Ge/MyDNA/Parent=           "World"
s:Ge/MyDNA/Material=          "G4_WATER"
s:Ge/MyDNA/AssignToRegionNamed  = "DNARegion"
i:Ge/MyDNA/NumberOfBasePairs= 100

# Material for volumes in strand 1
s:Ma/G4_WATER_MODIFIED_1/CloneFromMaterial = "G4_WATER"
d:Ma/G4_WATER_MODIFIED_1/CloneWithDensity  = 1.0 g/cm3

# Auxiliar material for volumes in strand 2
s:Ma/G4_WATER_MODIFIED_2/CloneFromMaterial = "G4_WATER_MODIFIED_1"
d:Ma/G4_WATER_MODIFIED_2/CloneWithDensity  = 1.0 g/cm3

s:Ge/MyDNA/Base/Material="G4_WATER"
s:Ge/MyDNA/BasePair/Material="G4_WATER_MODIFIED_1"
s:Ge/MyDNA/BasePair/Color="yellow"
s:Ge/MyDNA/BasePair/DrawingStyle="solid"
s:Ge/MyDNA/Backbone1/Material="G4_WATER_MODIFIED_1"
s:Ge/MyDNA/Backbone1/Color="red"
s:Ge/MyDNA/Backbone1/DrawingStyle="solid"
s:Ge/MyDNA/Backbone2/Material="G4_WATER_MODIFIED_2"
s:Ge/MyDNA/Backbone2/Color="blue"
s:Ge/MyDNA/Backbone2/DrawingStyle="solid"
d:Ge/MyDNA/RotX = 90 deg

# SOURCE 


s:So/RadionuclideSource/Type 					= "Isotropic"
s:So/RadionuclideSource/Component 				= "BeamPosition"
s:So/RadionuclideSource/BeamParticle 			= "GenericIon(89, 225)"
d:So/RadionuclideSource/BeamEnergy 		= 0 MeV
i:So/RadionuclideSource/NumberOfHistoriesInRun = 200
d:Ge/BeamPosition/TransZ = 0. mm
d:Ge/BeamPosition/TransY = 0 um



# PHYSICS 

sv:Ph/Default/Modules       =  3 "g4decay" "g4radioactivedecay" "TsEmDNAPhysics" "TsEmDNAChemistry"
s:Ph/Default/Electron/SetElasticScatteringModel = "CPA100"

#
includeFile											= SupportFiles/TOPASDefaultReactions.txt
s:Ch/ChemistryName = "TOPASChemistry"
b:Ch/TOPASChemistry/ChemicalStageTransportActive = "True"
d:Ch/TOPASChemistry/ChemicalStageTimeEnd = 1 ns



# SCORER

s:Sc/DNADamageScorer/Quantity				= "DNADamageStepByStep"
includeFile									= SupportFiles/DNAScorerStepByStep.txt
s:Sc/DNADamageScorer/Component 				= "MyDNA"
i:Sc/DNADamageScorer/NumberOfHistoriesInRun = So/RadionuclideSource/NumberOfHistoriesInRun
i:Sc/DNADamageScorer/BasePairPositionAtGeometricHierarchy = 0
sv:Sc/DNADamageScorer/Strand1MaterialNames  = 1 "G4_WATER_MODIFIED_1"
sv:Sc/DNADamageScorer/Strand2MaterialNames  = 1 "G4_WATER_MODIFIED_2"
s:Sc/DNADamageScorer/PrimaryParticle		= So/RadionuclideSource/BeamParticle
d:Sc/DNADamageScorer/MeanEnergy				= So/RadionuclideSource/BeamEnergy MeV



s:Sc/DBSCAN/Quantity = "DBSCAN"
s:Sc/DBSCAN/Component  = "MyDNA"
s:Sc/DBSCAN/OutputFile = "Ac_DBSCAN_plasmid_200H"
s:Sc/DBSCAN/OutputType = "ROOT"
b:Sc/DBSCAN/OutputToConsole = "True"
s:Sc/DBSCAN/IfOutputFileAlreadyExists = "Increment"
# DBSCAN configuration parameters
d:Sc/DBSCAN/MinimumDistanceForDSB       = 3.2 nm  # Distance betwen SSB to form a DSB ~10 bp
u:Sc/DBSCAN/SampleHitsWithProbability   = 0.5    # Hits are scorer with 16% probability
d:Sc/DBSCAN/LowerEnergyForSamplingSSB   = 5.0 eV  # Hits are sampled from a ramp distribution between
d:Sc/DBSCAN/UpperEnergyForSamplingSSB   = 37.5 eV # these two values: 5.0 eV -> 0.0; 37.5 eV -> 1.0

i:Sc/DBSCAN/MinimumNumberofSSBtoFormDSB = 2       # Minimum number of SSB to form a DSB
b:Sc/DBSCAN/PropagateToChildren         = "True"
s:Sc/RootFileName = Sc/DBSCAN/OutputFile


# VISUALIZATION

# s:Gr/View/Type			= "OpenGL"
# s:Gr/View/ColorBy       = "ParticleType"
# # s:Gr/View/ColorBy       = "charge"
# # sv:Gr/View/ColorByChargeColors = 3 "yellow" "aqua" "blue"
# # s:Ge/MyDNA/BasePair/DrawingStyle="solid"
# # s:Ge/MyDNA/Backbone1/Color="red"
# # s:Ge/MyDNA/Backbone1/DrawingStyle="solid"
# # s:Ge/MyDNA/Backbone2/Color="blue"
# # s:Ge/MyDNA/Backbone2/DrawingStyle="solid"
# # # sv:Gr/View/ColorByParticleTypeNames = 5 "e-" "gamma" "proton" "alpha" "neutron"
# # # sv:Gr/View/ColorByParticleTypeColors = 5 "green" "yellow" "blue" "red" "brown"
# sv:Gr/view/ColorByParticleTypeNames = 12 "alpha" "e-" "gamma" "Hydroxil" "SolvatedElectron" "HydrogenPeroxide" "Hydrogen" "DiHydrogen" "Oxygen" "SuperoxideAnion" "Hydroperoxy" "Dioxidanide"
# sv:Gr/view/ColorByParticleTypeColors = 12 "yellow" "red" "green" "violet" "magenta" "grass" "blue" "aqua" "white" "purple" "lightblue" "blue"
# b:Ts/UseQt              = "True"

i:Ts/Seed = 90541
i:Ts/NumberOfThreads = 0

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Physics

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[jschuemann]

Hi,
this is a good question. In fact, we often change the DNA representations and energy thresholds, but sometimes don't consider the consequences.
For any simulation, it is good to have an 'anker point', i.e., some data that all other data relates to and that you can fit your geometry and scoring parameters to. These values should also reproduce other data, e.g., the ratios of indirect to direct breaks etc.
The choice of your parameters is a mix of fit to data and best guesses, esp. when considering geometric representations since those are not really what DNA looks like.
Best
JAn

[ShahinGHD]

Hello Dr. Schuemann,
Thank you for your answer. Your reply has important points and was enlightening. The one that sticks to mind. I totally agree.

Thank you so much.
Regards,

Shahin