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2229 lines (1944 loc) · 67.6 KB
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import math
import random
import itertools
import operator
import copy
ln2 = math.log(2)
#immune shape space parameters
gene_len = 20 #see Smith and Perelson PNAS 1999
gene_vocab = 4 #see Smith and Perelson PNAS 1999
max_dist = 7
min_dist = 4
germline_affinity = 6
isotype_position = gene_len+1
#immune system parameters
differentiation_rate = 0.10 #see (1 - recycling rate) Oprea & Perelson J. Immunology 1997
mutation_rate = 0.1 #see Oprea & Perelson J. Immunology 1997, originally 0.1
isotype_rate = 0.10 #originally 0.0
reverse_rate = 0.10
lethal_fraction = 0.0
#########################################
##ANTIGEN BINDING AFFINITY FUNCTIONS
#########################################
def BindingAffinity( phenotype, affinity_factor ):
#right now binding affinity scales by ~1 with frequency of phenotype
if (phenotype <= min_dist):
return math.pow(affinity_factor, germline_affinity - (float(min_dist)))
elif (phenotype <= max_dist):
return math.pow(affinity_factor, germline_affinity - (float(phenotype)))
else:
return 0.0
#pre-calculated binding affinities for computational efficiency
class BindingAffinityPrecalc:
def __init__( self ):
self._BA_list = []
self._aff = []
def add_aff( self, value ):
BA_array = []
for i in range(0, max_dist+1):
BA_array.append( BindingAffinity(i, value) )
self._aff.append( value )
self._BA_list.append( BA_array )
print("ADDING AFF VALUE " + str( value ))
def aff_value( self, value ):
try:
i = self._aff.index( value )
return i
except ValueError:
self.add_aff( value )
return self._aff.index( value )
def get_BA( self, phenotype, affinity_factor ):
if (phenotype <= max_dist):
BA_array = self._BA_list[self.aff_value( affinity_factor )]
return BA_array[phenotype]
else:
return 0.0
BA = BindingAffinityPrecalc()
def BindingAffinity_Pre( phenotype, affinity_factor):
return BA.get_BA( phenotype, affinity_factor)
#apparent size refers to the concentration of a given species (i.e. B cells)
#normalized by the binding affinity
def ApparentSize( value, phenotype, aff_factor ):
if (float(phenotype) <= max_dist):
n = float(value) * BindingAffinity_Pre( phenotype, aff_factor )
return n
else:
return 0.0
#########################################
##BCR GENE FUNCTIONS
#########################################
def GeneRandom( ):
sequence = ""
for i in range( 0, gene_len ):
sequence += str(random.randint( 1,gene_vocab ))
sequence += 'M' #add isotype
return sequence
def GeneMutate( sequence ):
mutation_position = random.randint( 1, gene_len )
out_seq = ""
for i in range( 0, gene_len ):
if ( i == mutation_position ):
out_seq += str(random.randint(1, gene_vocab))
else:
out_seq += sequence[i]
out_seq += sequence[isotype_position-1] #add isotype
return out_seq
def IsotypeSwitch( sequence ):
out_seq = ""
for i in range(0, gene_len):
out_seq += sequence[i]
out_seq += 'G' #add isotype
return out_seq
def GenePhenotype( sequence, antigen_in ):
ne = operator.ne
epitope = antigen_in.epitope_all()
dist = 999
for i in range( 0, len( epitope ) ):
hamming_dist = sum(map(ne, sequence, epitope[i].get_sequence()))
if (hamming_dist < dist ):
dist = hamming_dist
# phenotype = min( max_dist + 1, dist )
phenotype = dist
return phenotype
def GenePhenotypeEpitope( sequence, antigen_in ):
ne = operator.ne
epitope = antigen_in.epitope_all()
dist = 999
epitope_num = 999
for i in range( 0, len( epitope ) ):
hamming_dist = sum(map(ne, sequence, epitope[i].get_sequence()))
if (hamming_dist < dist ):
dist = hamming_dist
epitope_num = i
# phenotype = min( max_dist + 1, dist )
phenotype = dist
output = [phenotype, epitope_num]
return output
def GeneEpitope( sequence, antigen_list ):
ne = operator.ne
dist = 999
epitope_num = 999
for antigen in antigen_list:
epitope = antigen.epitope_all()
for i in range( 0, len( epitope ) ):
hamming_dist = sum(map(ne, sequence, epitope[i].get_sequence()))
if (hamming_dist < dist ):
dist = hamming_dist
epitope_num = i
return epitope_num
def GeneFromPhenotype( phenotype, antigen, ep_num ):
sequence = ""
rand_pos = []
for i in range(1, gene_len+1):
rand_pos.append( i )
random.shuffle(rand_pos)
num_match = gene_len - phenotype
epitope = antigen.epitope( ep_num ).get_sequence()
for i in range(0,gene_len):
if (rand_pos[i] <= num_match):
sequence += epitope[i]
else:
new_val = epitope[i]
while( new_val == epitope[i] ):
new_val = str(random.randint(1,gene_vocab))
sequence += new_val
sequence += 'M' #add isotype
return sequence
#########################################
##IMMUNE SYSTEM COMPONENT TYPES
#########################################
#Name: Population
#Desc: A base class that describes the population of a given immune system
# component. It is made up of subpopulations, each with their own genotype
# and size. There are two types of Populations, Antigen and BCell (see below).
class Population:
def __init__( self, name, value ):
self._name = name
self._value = value
self._type = ''
def set_type ( self, type ):
self._type = type
def set_size ( self, value ):
self._value = value
def size( self ):
return self._value
def decrease(self, n ):
self._value = self._value - n
def increase(self, n ):
self._value = self._value + n
def name(self):
return str(self._name)
#Name: GroupPopulation
#Desc: An aggregate population that is made up of individual Population objects
class GroupPopulation:
def __init__( self, name ):
self._name = name
self._pop = []
self._value = 0
def add_population( self, pop ):
self._pop.append(pop)
def calc_population( self ):
self._value = 0
for i in range(0, len(self._pop) ):
self._value += self._pop[i].size()
def size( self ):
self.calc_population()
return self._value
def length( self ):
return(len(self._pop))
def random_select( self ):
self.calc_population()
r = random.random()
select = 0.0
for i in range(0, len(self._pop)):
select += float(self._pop[i].size())/float(self._value)
if (r <= select ):
return i
break
def decrease( self, n ):
self._pop[ self.random_select() ].decrease(n)
def sub_decrease( self, i, n ):
self._pop[ i ]. decrease(n)
def increase( self, n ):
self._pop[ self.random_select() ].increase(n)
def sub_increase( self, i, n ):
self._pop[ i ].increase(n)
#Name: Epitope
#Desc: Defines a single epitope, which includes an epitope sequence (in immune shape space),
# as well as its relative immunogenicity and clearance rates
class Epitope:
def __init__( self, name, sequence, immunogenicity, clearance ):
self._name = name
self._sequence = sequence
self._immunogenicity = immunogenicity
self._clearance = clearance
def mutate( self ):
self._sequence = GeneMutate( self._sequence )
def randomize( self ):
self._sequence = GeneRandom()
def set_sequence( self, seq ):
self._sequence = seq
def get_sequence( self ):
return self._sequence
def get_name ( self ):
return self._name
def immunogenicity( self ):
return self._immunogenicity
def clearance( self ):
return self._clearance
def copy( self ):
return copy.copy(self)
#Name: Antigen
#Desc: Defines an antigen population, which is one type of immune system component. It is
# defined by a name, a population size, and an AntigenType
class Antigen( Population ):
def __init__( self, name, value, antigen ):
Population.__init__( self, name, value )
self._antigen = antigen
def change_antigen( self, new_antigen ):
self._antigen = new_antigen
def return_antigen( self ):
return self._antigen
#Name: AntigenType
#Desc: Defines an antigen type (such as a given antigen strain). This includes a name, a numerical
# antigenID, and a list of epitopes that make up the antigen
#note: in future version, antigenID should be set internally for ease of use
class AntigenType:
def __init__( self, name, antigenID ):
self._name = name
self._epitope_array = []
self._antigenID = antigenID
def add_epitope( self, ep ):
self._epitope_array.append( ep )
def epitope( self, r ):
return self._epitope_array[r]
def epitope_all( self ):
return self._epitope_array
def epitope_num( self ):
return len(self._epitope_array)
def reset_epitopes( self ):
self._epitope_array = []
def ID ( self ):
return self._antigenID
def get_name ( self ):
return self._name
#Name: Bcell
#Desc: Defines a B cell population. It is indexed by genotype, and keeps track of the genotype,
# the size of the genotype population, the Epitope that genotype recognizes, and the phenotype
# of that genotype with respect to all Antigens in the system.
class BCell( Population ):
def add_genotype( self, gene, n ):
self._genotype_list.append( gene )
epitope = GeneEpitope(gene, self._antigen_list)
self._epitope_list.append( epitope )
self._size_list.append( n )
for antigen in self._antigen_list:
phenotype = GenePhenotype(gene, antigen)
phenotype_list = self._phenotype_master[antigen.ID()]
phenotype_list.append( phenotype )
subpopulation = self._subpopulation_master[antigen.ID()]
subpopulation[epitope][phenotype] += n
def phenotype_size( self, phenotype, antigenID ):
pop_size = 0
phenotype_list = self._phenotype_master[antigenID]
for i in range(0, len(phenotype_list)):
if (phenotype_list[i] == phenotype):
pop_size += self._size_list[i]
return pop_size
def epitope_size( self, epitope ):
pop_size = 0
for i in range(0, len(self._epitope_list)):
if (self._epitope_list[i] == epitope):
pop_size += self._size_list[i]
return pop_size
def RealSizePhenotype( self, epitope, phenotype, type, antigenID):
subpopulation = self._subpopulation_master[antigenID]
n = subpopulation[epitope][phenotype]
alpha = 0.0
if (type == "immunogenicity"):
alpha = self._antigen_list[antigenID].epitope( epitope ).immunogenicity()
elif (type == "clearance"):
alpha = self._antigen_list[antigenID].epitope( epitope ).clearance()
else:
print( "ERROR in APPARENTSIZEPHENOTYPE")
real_size = n * alpha
return real_size
def ApparentSizePhenotype( self, epitope, phenotype, aff_factor, type, antigenID):
subpopulation = self._subpopulation_master[antigenID]
n = subpopulation[epitope][phenotype]
alpha = 0.0
if (type == "immunogenicity"):
alpha = self._antigen_list[antigenID].epitope( epitope ).immunogenicity()
elif (type == "clearance"):
alpha = self._antigen_list[antigenID].epitope( epitope ).clearance()
else:
print("ERROR in APPARENTSIZEPHENOTYPE")
app_size = ApparentSize( n, phenotype, aff_factor ) * alpha
return app_size
def ApparentSizeEpitope( self, epitope, aff_factor, type, antigenID):
app_size = 0.0
for i in range(0,8):
app_size += self.ApparentSizePhenotype( epitope, i, aff_factor, type, antigenID )
return app_size
def ApparentSizeAll( self, aff_factor, type, virus ):
antigenID = virus.return_antigen().ID()
app_size = 0.0
for i in range(0, self._antigen_list[0].epitope_num() ):
app_size += self.ApparentSizeEpitope( i, aff_factor, type, antigenID)
return app_size
def select_random( self ):
r = random.random()
outcome = float(0.0)
for i in range(0, len(self._genotype_list)):
outcome += float(self._size_list[i])/float(Population.size( self ))
if (r <= outcome):
return str(self._genotype_list[i])
break
print("ERROR: COULD NOT FIND RANDOM select random " + str(self.name()) )
def select_epitope_phenotype( self, epitope, phenotype, antigenID ):
r = random.random()
outcome = float(0.0)
subpopulation = self._subpopulation_master[antigenID]
phenotype_list = self._phenotype_master[antigenID]
pop_size = subpopulation[epitope][phenotype]
tot_size = 0
for i in range(0, len(self._genotype_list)):
#correct = 0.0
if (phenotype_list[i] == phenotype and self._epitope_list[i] == epitope ):
#correct = 1.0
tot_size += self._size_list[i]
outcome += (float(self._size_list[i]) )/float(pop_size)
if (r <= outcome):
return str(self._genotype_list[i])
break
print("ERROR: COULD NOT FIND ###RANDOM select phenotype " + str(self._name) + ' ' + str(r) + ' ' +str(outcome) + ' ' + ' ' + str(tot_size) + ' ' + str(pop_size))
def select_random_weighted( self, aff_factor, max_rate, type, agg_rate, antigen ):
#construct phenotype probability
r = random.random()
base_phenotype = 999
base_epitope = 999
total_p = 0.0
for i in range(0, antigen.epitope_num() ):
for j in range(0,8):
p_size = min(self.ApparentSizePhenotype( i, j, aff_factor, type, antigen.ID())*agg_rate , self.RealSizePhenotype(i, j, type, antigen.ID())*max_rate)
total_p += p_size
found_it = 1
outcome = 0.0
for i in range(0, antigen.epitope_num() ):
for j in range(0,8):
p_size = min(self.ApparentSizePhenotype( i, j, aff_factor, type, antigen.ID())*agg_rate , self.RealSizePhenotype(i, j, type, antigen.ID())*max_rate)
outcome += p_size/total_p
if (r <= outcome and found_it == 1):
base_epitope = i
base_phenotype = j
found_it = 0
if ( base_epitope == 999 or base_phenotype == 999):
print("ERROR PHENOTYPE/EPITOPE NOT SELECTED IN REACT")
subpopulation = self._subpopulation_master[antigen.ID()]
pop_size = subpopulation[base_epitope][base_phenotype]
if (pop_size <= 0):
print("ERROR: POPULATION SIZE FOR #PHENOTYPE " + str(base_phenotype) + " IS ZERO " + self.name() )
return self.select_epitope_phenotype( base_epitope, base_phenotype, antigen.ID() )
def diversity(self, threshold):
line_count = 0
for i in range(0, len(self._genotype_list)):
if (self._size_list[i] >= threshold):
line_count = line_count + 1
return line_count
def diversity2( self, threshold):
num = threshold * float(Population.size( self ))
sort_list = sorted( self._size_list, reverse = True )
gene_count = 0
pop_count = 0
for i in range(0, len(self._genotype_list)):
if (pop_count < num):
pop_count += sort_list[i]
gene_count += 1
return gene_count
def genotype_increase( self, gene, n):
Population.increase( self, n )
try:
i = self._genotype_list.index( gene )
self._size_list[i] += n
for antigen in self._antigen_list:
subpopulation = self._subpopulation_master[antigen.ID()]
phenotype_list = self._phenotype_master[antigen.ID()]
subpopulation[self._epitope_list[i]][phenotype_list[i]] += n
except ValueError:
self.add_genotype( gene, n )
def genotype_decrease( self, gene, n ):
Population.decrease(self, n )
try:
i = self._genotype_list.index( gene )
for antigen in self._antigen_list:
phenotype_list = self._phenotype_master[antigen.ID()]
subpopulation = self._subpopulation_master[antigen.ID()]
subpopulation[self._epitope_list[i]][phenotype_list[i]] -= n
if ((self._size_list[i] - n) <= 0):
self._size_list.pop(i)
self._genotype_list.pop(i)
self._epitope_list.pop(i)
for antigen in self._antigen_list:
phenotype_list = self._phenotype_master[antigen.ID()]
phenotype_list.pop(i)
else:
self._size_list[i] -= n
except ValueError:
print(str(self._name) + " "+ str(Population.size(self)) +str(gene)+" is not in the list!!")
def increase( self, n ):
# phenotype = 7
phenotype = random.randint( 7, gene_len )
r = random.random()
n_antigen = len(self._antigen_list)
n_epitope = len(self._antigen_list[0].epitope_all())
r_antigen = random.random()
r_epitope = random.random()
count = 0.0
antigen = 999
for i in range(0,n_antigen):
count = count + float(1.0/n_antigen)
if (r_antigen <= count and antigen == 999):
antigen = i
count = 0.0
epitope = 999
for i in range(0,n_epitope):
count = count + float(1.0/n_epitope)
if (r_epitope <= count and epitope == 999):
epitope = i
# epitope = 999
# if (r_epitope <= float(1.0/(n_antigen+1))):
# epitope = 0
# else:
# epitope = 1
base_gene = GeneFromPhenotype( phenotype, self._antigen_list[antigen], epitope )
self.genotype_increase( base_gene, n )
def decrease( self, n ):
self.genotype_decrease( self.select_random(), 1 )
def calc_crossreactivity_specificity( self, antigen_list ):
output = []
for i in range(0,60):
output.append(0)
for i in range(0, len(self._genotype_list)):
phen_epit1 = GenePhenotypeEpitope( self._genotype_list[i], self._antigen_list[0] )
phen_epit2 = GenePhenotypeEpitope( self._genotype_list[i], self._antigen_list[1] )
phen_epit3 = GenePhenotypeEpitope( self._genotype_list[i], self._antigen_list[2] )
phen_epit4 = GenePhenotypeEpitope( self._genotype_list[i], self._antigen_list[3] )
if (phen_epit1[0] <= max_dist and phen_epit2[0] <= max_dist and phen_epit3[0] <= max_dist and phen_epit4[0] <= max_dist):
if (phen_epit1[1] == 0 and phen_epit2[1] == 0 and phen_epit3[1] == 0 and phen_epit4[1] == 0):
output[0] += self._size_list[i]
elif (phen_epit1[1] == 1 and phen_epit2[1] == 1 and phen_epit3[1] == 1 and phen_epit4[1] == 1):
output[1] += self._size_list[i]
elif (phen_epit1[1] == 2 and phen_epit2[1] == 2 and phen_epit3[1] == 2 and phen_epit4[1] == 2):
output[2] += self._size_list[i]
elif (phen_epit1[1] == 3 and phen_epit2[1] == 3 and phen_epit3[1] == 3 and phen_epit4[1] == 3):
output[3] += self._size_list[i]
elif (phen_epit1[0] <= max_dist and phen_epit2[0] <= max_dist and phen_epit3[0] <= max_dist):
if (phen_epit1[1] == 0 and phen_epit2[1] == 0 and phen_epit3[1] == 0):
output[4] += self._size_list[i]
elif (phen_epit1[1] == 1 and phen_epit2[1] == 1 and phen_epit3[1] == 1):
output[5] += self._size_list[i]
elif (phen_epit1[1] == 2 and phen_epit2[1] == 2 and phen_epit3[1] == 2):
output[6] += self._size_list[i]
elif (phen_epit1[1] == 3 and phen_epit2[1] == 3 and phen_epit3[1] == 3):
output[7] += self._size_list[i]
elif (phen_epit1[0] <= max_dist and phen_epit2[0] <= max_dist and phen_epit4[0] <= max_dist):
if (phen_epit1[1] == 0 and phen_epit2[1] == 0 and phen_epit4[1] == 0):
coutput[8] += self._size_list[i]
elif (phen_epit1[1] == 1 and phen_epit2[1] == 1 and phen_epit4[1] == 1):
output[9] += self._size_list[i]
elif (phen_epit1[1] == 2 and phen_epit2[1] == 2 and phen_epit4[1] == 2):
output[10] += self._size_list[i]
elif (phen_epit1[1] == 3 and phen_epit2[1] == 3 and phen_epit4[1] == 3):
output[11] += self._size_list[i]
elif (phen_epit1[0] <= max_dist and phen_epit3[0] <= max_dist and phen_epit4[0] <= max_dist):
if (phen_epit1[1] == 0 and phen_epit3[1] == 0 and phen_epit4[1] == 0):
output[12] += self._size_list[i]
elif (phen_epit1[1] == 1 and phen_epi3[1] == 1 and phen_epit4[1] == 1):
output[13] += self._size_list[i]
elif (phen_epit1[1] == 2 and phen_epit3[1] == 2 and phen_epit4[1] == 2):
output[14] += self._size_list[i]
elif (phen_epit1[1] == 3 and phen_epit3[1] == 3 and phen_epit4[1] == 3):
output[15] += self._size_list[i]
elif (phen_epit2[0] <= max_dist and phen_epit3[0] <= max_dist and phen_epit4[0] <= max_dist):
if (phen_epit2[1] == 0 and phen_epit3[1] == 0 and phen_epit4[1] == 0):
output[16] += self._size_list[i]
elif (phen_epit2[1] == 1 and phen_epi3[1] == 1 and phen_epit4[1] == 1):
output[17] += self._size_list[i]
elif (phen_epit2[1] == 2 and phen_epit3[1] == 2 and phen_epit4[1] == 2):
output[18] += self._size_list[i]
elif (phen_epit2[1] == 3 and phen_epit3[1] == 3 and phen_epit4[1] == 3):
output[19] += self._size_list[i]
elif (phen_epit1[0] <= max_dist and phen_epit2[0] <= max_dist):
if (phen_epit1[1] == 0 and phen_epit2[1] == 0):
output[20] += self._size_list[i]
elif (phen_epit1[1] == 1 and phen_epi2[1] == 1):
output[21] += self._size_list[i]
elif (phen_epit1[1] == 2 and phen_epit2[1] == 2):
output[22] += self._size_list[i]
elif (phen_epit1[1] == 3 and phen_epit2[1] == 3):
output[23] += self._size_list[i]
elif (phen_epit1[0] <= max_dist and phen_epit3[0] <= max_dist):
if (phen_epit1[1] == 0 and phen_epit3[1] == 0):
output[24] += self._size_list[i]
elif (phen_epit1[1] == 1 and phen_epi3[1] == 1):
output[25] += self._size_list[i]
elif (phen_epit1[1] == 2 and phen_epit3[1] == 2):
output[26] += self._size_list[i]
elif (phen_epit1[1] == 3 and phen_epit3[1] == 3):
output[27] += self._size_list[i]
elif (phen_epit1[0] <= max_dist and phen_epit4[0] <= max_dist):
if (phen_epit1[1] == 0 and phen_epit4[1] == 0):
output[28] += self._size_list[i]
elif (phen_epit1[1] == 1 and phen_epi4[1] == 1):
output[29] += self._size_list[i]
elif (phen_epit1[1] == 2 and phen_epit4[1] == 2):
output[30] += self._size_list[i]
elif (phen_epit1[1] == 3 and phen_epit4[1] == 3):
output[31] += self._size_list[i]
elif (phen_epit2[0] <= max_dist and phen_epit3[0] <= max_dist):
if (phen_epit2[1] == 0 and phen_epit3[1] == 0):
output[32] += self._size_list[i]
elif (phen_epit2[1] == 1 and phen_epi3[1] == 1):
output[33] += self._size_list[i]
elif (phen_epit2[1] == 2 and phen_epit3[1] == 2):
output[34] += self._size_list[i]
elif (phen_epit2[1] == 3 and phen_epit3[1] == 3):
output[35] += self._size_list[i]
elif (phen_epit2[0] <= max_dist and phen_epit4[0] <= max_dist):
if (phen_epit2[1] == 0 and phen_epit4[1] == 0):
output[36] += self._size_list[i]
elif (phen_epit2[1] == 1 and phen_epi4[1] == 1):
output[37] += self._size_list[i]
elif (phen_epit2[1] == 2 and phen_epit4[1] == 2):
output[38] += self._size_list[i]
elif (phen_epit2[1] == 3 and phen_epit4[1] == 3):
output[39] += self._size_list[i]
elif (phen_epit3[0] <= max_dist and phen_epit4[0] <= max_dist):
if (phen_epit3[1] == 0 and phen_epit4[1] == 0):
output[40] += self._size_list[i]
elif (phen_epit3[1] == 1 and phen_epi4[1] == 1):
output[41] += self._size_list[i]
elif (phen_epit3[1] == 2 and phen_epit4[1] == 2):
output[42] += self._size_list[i]
elif (phen_epit3[1] == 3 and phen_epit4[1] == 3):
output[43] += self._size_list[i]
elif (phen_epit1[0] <= max_dist):
if (phen_epit1[1] == 0):
output[44] += self._size_list[i]
elif (phen_epit1[1] == 1):
output[45] += self._size_list[i]
elif (phen_epit1[1] == 2):
output[46] += self._size_list[i]
elif (phen_epit1[1] == 3):
output[47] += self._size_list[i]
elif (phen_epit2[0] <= max_dist):
if (phen_epit2[1] == 0):
output[48] += self._size_list[i]
elif (phen_epit2[1] == 1):
output[49] += self._size_list[i]
elif (phen_epit2[1] == 2):
output[50] += self._size_list[i]
elif (phen_epit2[1] == 3):
output[51] += self._size_list[i]
elif (phen_epit3[0] <= max_dist):
if (phen_epit3[1] == 0):
output[52] += self._size_list[i]
elif (phen_epit3[1] == 1):
output[53] += self._size_list[i]
elif (phen_epit3[1] == 2):
output[54] += self._size_list[i]
elif (phen_epit3[1] == 3):
output[55] += self._size_list[i]
elif (phen_epit4[0] <= max_dist):
if (phen_epit4[1] == 0):
output[56] += self._size_list[i]
elif (phen_epit4[1] == 1):
output[57] += self._size_list[i]
elif (phen_epit4[1] == 2):
output[58] += self._size_list[i]
elif (phen_epit4[1] == 3):
output[59] += self._size_list[i]
return output
def calc_crossreactivity( self, antigen_list ):
output = []
for i in range(0,16):
output.append(0)
for i in range(0, len(self._genotype_list)):
phenotype1 = GenePhenotype( self._genotype_list[i], self._antigen_list[0] )
phenotype2 = GenePhenotype( self._genotype_list[i], self._antigen_list[1] )
phenotype3 = GenePhenotype( self._genotype_list[i], self._antigen_list[2] )
phenotype4 = GenePhenotype( self._genotype_list[i], self._antigen_list[3] )
if (phenotype1 <= max_dist and phenotype2 <= max_dist and phenotype3 <= max_dist and phenotype4 <= max_dist):
output[0] += self._size_list[i]
elif (phenotype1 <= max_dist and phenotype2 <= max_dist and phenotype3 <= max_dist):
output[1] += self._size_list[i]
elif (phenotype1 <= max_dist and phenotype2 <= max_dist and phenotype4 <= max_dist):
output[2] += self._size_list[i]
elif (phenotype1 <= max_dist and phenotype3 <= max_dist and phenotype4 <= max_dist):
output[3] += self._size_list[i]
elif (phenotype2 <= max_dist and phenotype3 <= max_dist and phenotype4 <= max_dist):
output[4] += self._size_list[i]
elif (phenotype1 <= max_dist and phenotype2 <= max_dist):
output[5] += self._size_list[i]
elif (phenotype1 <= max_dist and phenotype3 <= max_dist):
output[6] += self._size_list[i]
elif (phenotype1 <= max_dist and phenotype4 <= max_dist):
output[7] += self._size_list[i]
elif (phenotype2 <= max_dist and phenotype3 <= max_dist):
output[8] += self._size_list[i]
elif (phenotype2 <= max_dist and phenotype4 <= max_dist):
output[9] += self._size_list[i]
elif (phenotype3 <= max_dist and phenotype4 <= max_dist):
output[10] += self._size_list[i]
elif (phenotype1 <= max_dist):
output[11] += self._size_list[i]
elif (phenotype2 <= max_dist):
output[12] +=self._size_list[i]
elif (phenotype3 <= max_dist):
output[13] +=self._size_list[i]
elif (phenotype4 <= max_dist):
output[14] +=self._size_list[i]
else:
output[15] +=self._size_list[i]
return output
def calc_transcend( self, antigen_list ):
output = []
for i in range(0,len(antigen_list)+1):
output.append(0)
for i in range(0, len(self._genotype_list)):
strain_num = 0
#for antigen in self._antigen_list:
for j in range(0, len(antigen_list)-1):
phen = GenePhenotype( self._genotype_list[i], self._antigen_list[j] )
if (phen <= max_dist):
strain_num += 1
output[strain_num] += self._size_list[i]
return output
#we need to work out depletion and neutralization
def calc_neutralization( self, antigen_list ):
spec1_num = 0
spec2_num = 0
spec3_num = 0
spec4_num = 0
for i in range(0, len(self._genotype_list)):
phenotype1 = GenePhenotype( self._genotype_list[i], self._antigen_list[0] )
phenotype2 = GenePhenotype( self._genotype_list[i], self._antigen_list[1] )
phenotype3 = GenePhenotype( self._genotype_list[i], self._antigen_list[2] )
phenotype4 = GenePhenotype( self._genotype_list[i], self._antigen_list[3] )
if (phenotype1 <= max_dist):
spec1_num += self._size_list[i]*BindingAffinity_Pre(phenotype1, 2.5)
if (phenotype2 <= max_dist):
spec2_num += self._size_list[i]*BindingAffinity_Pre(phenotype2, 2.5)
if (phenotype3 <= max_dist):
spec3_num += self._size_list[i]*BindingAffinity_Pre(phenotype3, 2.5)
if (phenotype4 <= max_dist):
spec4_num += self._size_list[i]*BindingAffinity_Pre(phenotype4, 2.5)
output = [spec1_num, spec2_num, spec3_num, spec4_num]
return output
def calc_cross(self, antigen1, epitope):
subpopulation = self._subpopulation_master[antigen1.ID()]
pop = [0,0,0,0]
for phenotype in range(0, 5):
pop[0] = pop[0] + subpopulation[epitope][phenotype]
pop[1] = subpopulation[epitope][5]
pop[2] = subpopulation[epitope][6]
pop[3] = subpopulation[epitope][7]
return pop
def calc_isotype( self ):
g_num = 0
for i in range(0, len(self._genotype_list)):
gene = self._genotype_list[i]
if (gene[isotype_position - 1] == 'G'):
g_num += self._size_list[i]
m_num = self.size() - g_num
output = [m_num, g_num]
return output
#function for randomly generating the starting population of naive B cells
def generate_population( self, value):
for antigen in self._antigen_list:
n_epitope = len(antigen.epitope_all())
for j in range(0, n_epitope):
for phenotype in range(7,8):
current_pop = 0
pop = int(math.floor(math.pow(10,-1*(5+max_dist-phenotype)) * float(value))/n_epitope)
while (current_pop < pop):
current_pop += 1
base_gene = GeneFromPhenotype( phenotype, antigen, j )
min_phen = 7
for k in range(0,len(self._antigen_list)):
phenotype1 = GenePhenotype( base_gene, self._antigen_list[k] )
if (phenotype1 < min_phen ):
min_phen = phenotype1
if (min_phen == 7):
self.genotype_increase(base_gene, 1)
# print( base_gene )
high_pop = int(math.floor(math.pow(10,-1*(5+max_dist-phenotype)) * float(value))) * len(self._antigen_list) * 2
for i in range(0, high_pop):
for antigen in self._antigen_list:
n_epitope = len(antigen.epitope_all())
for j in range(0, n_epitope):
for phenotype in range(7,8):
pop = int(math.floor(math.pow(10,-1*(5+max_dist-phenotype)) * float(value))/n_epitope)
subpopulation = self._subpopulation_master[ antigen.ID() ]
current_pop = subpopulation[j][phenotype]
if ( subpopulation[j][phenotype] > pop ):
del_gene = self.select_epitope_phenotype(j, phenotype, antigen.ID())
self.genotype_decrease( del_gene, 1)
def generate_population_new( self, value):
for antigen in self._antigen_list:
n_epitope = len(antigen.epitope_all())
for j in range(0, n_epitope):
for phenotype in range(7,20):
current_pop = 0
pop = int((math.floor(math.pow(10,-1*(5+max_dist-7.0)) * float(value))/n_epitope)/1.0)
while (current_pop < pop):
current_pop += 1
base_gene = GeneFromPhenotype( phenotype, antigen, j )
min_phen = phenotype
for k in range(0,len(self._antigen_list)):
phenotype1 = GenePhenotype( base_gene, self._antigen_list[k] )
if (phenotype1 < min_phen ):
min_phen = phenotype1
if (min_phen == phenotype):
self.genotype_increase(base_gene, 1)
# print(current_pop, base_gene )
high_pop = int(math.floor(math.pow(10,-1*(5+max_dist-7.0)) * float(value))) * len(self._antigen_list) * 2
for i in range(0, high_pop):
for antigen in self._antigen_list:
n_epitope = len(antigen.epitope_all())
for j in range(0, n_epitope):
for phenotype in range(7,20):
pop = int((math.floor(math.pow(10,-1*(5+max_dist-7.0)) * float(value))/n_epitope)/1.0)
subpopulation = self._subpopulation_master[ antigen.ID() ]
current_pop = subpopulation[j][phenotype]
if ( subpopulation[j][phenotype] > pop ):
del_gene = self.select_epitope_phenotype(j, phenotype, antigen.ID())
self.genotype_decrease( del_gene, 1)
def return_gene_list( self ):
return self._genotype_list
def return_size_list( self ):
return self._size_list
def __init__( self, name, value, antigen_list ):
Population.__init__( self, name, 0 )
Population.set_type(self, "bcell")
self._genotype_list = []
self._epitope_list = []
self._size_list = []
self._antigen_list = antigen_list
epitope_num = antigen_list[0].epitope_num()
#for each antigen
self._phenotype_master = []
self._subpopulation_master = []
for antigen in antigen_list:
phenotype_list = []
subpopulation = [[0]*20 for x in range(epitope_num)]
self._phenotype_master.append(phenotype_list)
self._subpopulation_master.append(subpopulation)
self.generate_population_new( value )
#########################################
## REACTIONS TYPES
#########################################
#Name: OrderZero
#Desc: Defines the base class for zero-order reactions
class OrderZero:
def __init__( self, name, k ):
self._name = name
self._k = ln2 * float( k )
self.__rate = 0
def rate( self ):
self.__rate = self._k
return self.__rate
#Name: OrderOne
#Desc: Defines the base class for first-order reactions
class OrderOne:
def __init__( self, name, k, A ):
self._name = name
self._k = ln2*float(k)
self._A = A
def rate( self ):
self.__rate = self._k * self._A.size()
return self.__rate
#Name: OrderTwo
#Desc: Defines the base class for second-order reactions
class OrderTwo:
def __init__( self, name, k, A, B):
self._name = name
self._k = ln2*float(k)
self._A = A
self._B = B
def rate( self ):
self.__rate = self._k * self._A.size() * self._B.size()
return self.__rate
#Name: OrderTwoPhenotype
#Desc: Defines the base class for second-order reactions where the reaction rate is the
# result of a heterogenious population, with varying phenotypes (such as B cell stimulation)
class OrderTwoPhenotype:
def __init__( self, name, k, A, B, max_rate, aff_factor, type ):
self._name = name
self._k = ln2*float(k)
self._A = A
self._B = B
self._max_rate = ln2*max_rate
self._aff_factor = aff_factor
BA.aff_value( aff_factor )
self._type = type
def rate( self ):
self.__rate = 0.0
if (self._B.size() > 0):
Bcell_app = self._B.ApparentSizeAll( self._aff_factor, self._type, self._A )
self.__rate = min(self._A.size() * Bcell_app * self._k, self._B.size() * self._max_rate)
return self.__rate
#########################################
## IMMUNE SYSTEM REACTIONS
#########################################
#Name: Stimulation
#Desc: Defines the reaction for B cell stimulation
# i.e. B + Ag -> B* + Ag
class Stimulation( OrderTwoPhenotype ):
def __init__( self, name, k, A, B, C, max_rate, aff_factor, type ):
OrderTwoPhenotype.__init__(self, name, k, A, B, max_rate, aff_factor, type)
self.A = A
self.B = B
self.C = C
self.aff_factor = aff_factor
self.type = type
self.max_rate = max_rate
self.k = k
def react( self ):
antigen = self.A.return_antigen()
agg_rate = self.k * self.A.size()
base_gene = self.B.select_random_weighted( self.aff_factor, self.max_rate, self.type, agg_rate, antigen )
self.B.genotype_decrease(base_gene, 1 )
self.C.genotype_increase(base_gene, 1 )
class MStimulation( OrderTwoPhenotype ):
def __init__( self, name, k, A, B, C, D, max_rate, aff_factor, type ):
OrderTwoPhenotype.__init__(self, name, k, A, B, max_rate, aff_factor, type)
self.A = A
self.B = B