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scsim.py
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scsim.py
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import pandas as pd
import numpy as np
import sys
class scsim:
def __init__(self, ngenes=10000, ncells=100, seed=757578,
mean_rate=.3, mean_shape=.6, libloc=11, libscale=0.2,
expoutprob=.05, expoutloc=4, expoutscale=0.5, ngroups=1,
diffexpprob=.1, diffexpdownprob=.5,
diffexploc=.1, diffexpscale=.4, bcv_dispersion=.1,
bcv_dof=60, ndoublets=0, groupprob=None,
nproggenes=None, progdownprob=None, progdeloc=None,
progdescale=None, proggoups=None, progcellfrac=None,
minprogusage=.2, maxprogusage=.8):
self.ngenes = ngenes
self.ncells = ncells
self.seed = seed
self.mean_rate = mean_rate
self.mean_shape = mean_shape
self.libloc = libloc
self.libscale = libscale
self.expoutprob = expoutprob
self.expoutloc = expoutloc
self.expoutscale = expoutscale
self.ngroups = ngroups
self.diffexpprob = diffexpprob
self.diffexpdownprob = diffexpdownprob
self.diffexploc = diffexploc
self.diffexpscale = diffexpscale
self.bcv_dispersion = bcv_dispersion
self.bcv_dof = bcv_dof
self.ndoublets = ndoublets
self.init_ncells = ncells+ndoublets
self.nproggenes=nproggenes
self.progdownprob=progdownprob
self.progdeloc=progdeloc
self.progdescale=progdescale
self.proggoups=proggoups
self.progcellfrac = progcellfrac
self.minprogusage = minprogusage
self.maxprogusage = maxprogusage
if groupprob is None:
self.groupprob = [1/float(self.ngroups)]*self.ngroups
elif (len(groupprob) == self.ngroups) & (np.abs(np.sum(groupprob) - 1) < (10**-6)):
self.groupprob = groupprob
else:
sys.exit('Invalid groupprob input')
def simulate(self):
np.random.seed(self.seed)
print('Simulating cells')
self.cellparams = self.get_cell_params()
print('Simulating gene params')
self.geneparams = self.get_gene_params()
if (self.nproggenes is not None) and (self.nproggenes > 0):
print('Simulating program')
self.simulate_program()
print('Simulating DE')
self.sim_group_DE()
print('Simulating cell-gene means')
self.cellgenemean = self.get_cell_gene_means()
if self.ndoublets > 0:
print('Simulating doublets')
self.simulate_doublets()
print('Adjusting means')
self.adjust_means_bcv()
print('Simulating counts')
self.simulate_counts()
def simulate_counts(self):
'''Sample read counts for each gene x cell from Poisson distribution
using the variance-trend adjusted updatedmean value'''
self.counts = pd.DataFrame(np.random.poisson(lam=self.updatedmean),
index=self.cellnames, columns=self.genenames)
def adjust_means_bcv(self):
'''Adjust cellgenemean to follow a mean-variance trend relationship'''
self.bcv = self.bcv_dispersion + (1 / np.sqrt(self.cellgenemean))
chisamp = np.random.chisquare(self.bcv_dof, size=self.ngenes)
self.bcv = self.bcv*np.sqrt(self.bcv_dof / chisamp)
self.updatedmean = np.random.gamma(shape=1/(self.bcv**2),
scale=self.cellgenemean*(self.bcv**2))
self.bcv = pd.DataFrame(self.bcv, index=self.cellnames, columns=self.genenames)
self.updatedmean = pd.DataFrame(self.updatedmean, index=self.cellnames,
columns=self.genenames)
def simulate_doublets(self):
## Select doublet cells and determine the second cell to merge with
d_ind = sorted(np.random.choice(self.ncells, self.ndoublets,
replace=False))
d_ind = ['Cell%d' % (x+1) for x in d_ind]
self.cellparams['is_doublet'] = False
self.cellparams.loc[d_ind, 'is_doublet'] = True
extraind = self.cellparams.index[-self.ndoublets:]
group2 = self.cellparams.ix[extraind, 'group'].values
self.cellparams['group2'] = -1
self.cellparams.loc[d_ind, 'group2'] = group2
## update the cell-gene means for the doublets while preserving the
## same library size
dmean = self.cellgenemean.loc[d_ind,:].values
dmultiplier = .5 / dmean.sum(axis=1)
dmean = np.multiply(dmean, dmultiplier[:, np.newaxis])
omean = self.cellgenemean.loc[extraind,:].values
omultiplier = .5 / omean.sum(axis=1)
omean = np.multiply(omean, omultiplier[:,np.newaxis])
newmean = dmean + omean
libsize = self.cellparams.loc[d_ind, 'libsize'].values
newmean = np.multiply(newmean, libsize[:,np.newaxis])
self.cellgenemean.loc[d_ind,:] = newmean
## remove extra doublet cells from the data structures
self.cellgenemean.drop(extraind, axis=0, inplace=True)
self.cellparams.drop(extraind, axis=0, inplace=True)
self.cellnames = self.cellnames[0:self.ncells]
def get_cell_gene_means(self):
'''Calculate each gene's mean expression for each cell while adjusting
for the library size'''
group_genemean = self.geneparams.loc[:,[x for x in self.geneparams.columns if ('_genemean' in x) and ('group' in x)]].T.astype(float)
group_genemean = group_genemean.div(group_genemean.sum(axis=1), axis=0)
ind = self.cellparams['group'].apply(lambda x: 'group%d_genemean' % x)
if self.nproggenes == 0:
cellgenemean = group_genemean.loc[ind,:].astype(float)
cellgenemean.index = self.cellparams.index
else:
noprogcells = self.cellparams['has_program']==False
hasprogcells = self.cellparams['has_program']==True
print(' - Getting mean for activity program carrying cells')
progcellmean = group_genemean.loc[ind[hasprogcells], :]
progcellmean.index = ind.index[hasprogcells]
progcellmean = progcellmean.multiply(1-self.cellparams.loc[hasprogcells, 'program_usage'], axis=0)
progmean = self.geneparams.loc[:,['prog_genemean']]
progmean = progmean.div(progmean.sum(axis=0), axis=1)
progusage = self.cellparams.loc[progcellmean.index, ['program_usage']]
progusage.columns = ['prog_genemean']
progcellmean += progusage.dot(progmean.T)
progcellmean = progcellmean.astype(float)
print(' - Getting mean for non activity program carrying cells')
noprogcellmean = group_genemean.loc[ind[noprogcells],:]
noprogcellmean.index = ind.index[noprogcells]
cellgenemean = pd.concat([noprogcellmean, progcellmean], axis=0)
del(progcellmean, noprogcellmean)
cellgenemean = cellgenemean.reindex(index=self.cellparams.index)
print(' - Normalizing by cell libsize')
normfac = (self.cellparams['libsize'] / cellgenemean.sum(axis=1)).values
for col in cellgenemean.columns:
cellgenemean[col] = cellgenemean[col].values*normfac
#cellgenemean = cellgenemean.multiply(normfac, axis=0).astype(float)
return(cellgenemean)
def get_gene_params(self):
'''Sample each genes mean expression from a gamma distribution as
well as identifying outlier genes with expression drawn from a
log-normal distribution'''
basegenemean = np.random.gamma(shape=self.mean_shape,
scale=1./self.mean_rate,
size=self.ngenes)
is_outlier = np.random.choice([True, False], size=self.ngenes,
p=[self.expoutprob,1-self.expoutprob])
outlier_ratio = np.ones(shape=self.ngenes)
outliers = np.random.lognormal(mean=self.expoutloc,
sigma=self.expoutscale,
size=is_outlier.sum())
outlier_ratio[is_outlier] = outliers
gene_mean = basegenemean.copy()
median = np.median(basegenemean)
gene_mean[is_outlier] = outliers*median
self.genenames = ['Gene%d' % i for i in range(1, self.ngenes+1)]
geneparams = pd.DataFrame([basegenemean, is_outlier, outlier_ratio, gene_mean],
index=['BaseGeneMean', 'is_outlier', 'outlier_ratio', 'gene_mean'],
columns=self.genenames).T
return(geneparams)
def get_cell_params(self):
'''Sample cell group identities and library sizes'''
groupid = self.simulate_groups()
libsize = np.random.lognormal(mean=self.libloc, sigma=self.libscale,
size=self.init_ncells)
self.cellnames = ['Cell%d' % i for i in range(1, self.init_ncells+1)]
cellparams = pd.DataFrame([groupid, libsize],
index=['group', 'libsize'],
columns=self.cellnames).T
cellparams['group'] = cellparams['group'].astype(int)
return(cellparams)
def simulate_program(self):
## Simulate the program gene expression
self.geneparams['prog_gene'] = False
proggenes = self.geneparams.index[-self.nproggenes:]
self.geneparams.loc[proggenes, 'prog_gene'] = True
DEratio = np.random.lognormal(mean=self.progdeloc,
sigma=self.progdescale,
size=self.nproggenes)
DEratio[DEratio<1] = 1 / DEratio[DEratio<1]
is_downregulated = np.random.choice([True, False],
size=len(DEratio),
p=[self.progdownprob,
1-self.progdownprob])
DEratio[is_downregulated] = 1. / DEratio[is_downregulated]
all_DE_ratio = np.ones(self.ngenes)
all_DE_ratio[-self.nproggenes:] = DEratio
prog_mean = self.geneparams['gene_mean']*all_DE_ratio
self.geneparams['prog_genemean'] = prog_mean
## Assign the program to cells
self.cellparams['has_program'] = False
if self.proggoups is None:
## The program is active in all cell types
self.proggoups = np.arange(1, self.ngroups+1)
self.cellparams.loc[:, 'program_usage'] = 0
for g in self.proggoups:
groupcells = self.cellparams.index[self.cellparams['group']==g]
hasprog = np.random.choice([True, False], size=len(groupcells),
p=[self.progcellfrac,
1-self.progcellfrac])
self.cellparams.loc[groupcells[hasprog], 'has_program'] = True
usages = np.random.uniform(low=self.minprogusage,
high=self.maxprogusage,
size=len(groupcells[hasprog]))
self.cellparams.loc[groupcells[hasprog], 'program_usage'] = usages
def simulate_groups(self):
'''Sample cell group identities from a categorical distriubtion'''
groupid = np.random.choice(np.arange(1, self.ngroups+1),
size=self.init_ncells, p=self.groupprob)
self.groups = np.unique(groupid)
return(groupid)
def sim_group_DE(self):
'''Sample differentially expressed genes and the DE factor for each
cell-type group'''
groups = self.cellparams['group'].unique()
if self.nproggenes>0:
proggene = self.geneparams['prog_gene'].values
else:
proggene = np.array([False]*self.geneparams.shape[0])
for group in self.groups:
isDE = np.random.choice([True, False], size=self.ngenes,
p=[self.diffexpprob,1-self.diffexpprob])
isDE[proggene] = False # Program genes shouldn't be differentially expressed between groups
DEratio = np.random.lognormal(mean=self.diffexploc,
sigma=self.diffexpscale,
size=isDE.sum())
DEratio[DEratio<1] = 1 / DEratio[DEratio<1]
is_downregulated = np.random.choice([True, False],
size=len(DEratio),
p=[self.diffexpdownprob,1-self.diffexpdownprob])
DEratio[is_downregulated] = 1. / DEratio[is_downregulated]
all_DE_ratio = np.ones(self.ngenes)
all_DE_ratio[isDE] = DEratio
group_mean = self.geneparams['gene_mean']*all_DE_ratio
deratiocol = 'group%d_DEratio' % group
groupmeancol = 'group%d_genemean' % group
self.geneparams[deratiocol] = all_DE_ratio
self.geneparams[groupmeancol] = group_mean