def test_null_distribution_lrt(self,
n_cells: int = 2000,
n_genes: int = 100):
"""
Test if de.test.continuous() generates a uniform p-value distribution in lrt
if it is given data simulated based on the null model. Returns the p-value
of the two-side Kolmgorov-Smirnov test for equality of the observed
p-value distriubution and a uniform distribution.
:param n_cells: Number of cells to simulate (number of observations per test).
:param n_genes: Number of genes to simulate (number of tests).
"""
logging.getLogger("tensorflow").setLevel(logging.INFO)
logging.getLogger("batchglm").setLevel(logging.INFO)
logging.getLogger("diffxpy").setLevel(logging.WARNING)
sim = Simulator(num_observations=n_cells, num_features=n_genes)
sim.generate_sample_description(num_batches=0, num_conditions=0)
sim.generate()
random_sample_description = pd.DataFrame(
{"pseudotime": np.random.random(size=sim.nobs)})
test = de.test.continuous_1d(
data=sim.X,
continuous="pseudotime",
df=3,
formula_loc="~ 1 + pseudotime",
formula_scale="~ 1",
factor_loc_totest="pseudotime",
test="lrt",
sample_description=random_sample_description,
quick_scale=False,
batch_size=None,
training_strategy="DEFAULT",
dtype="float64")
summary = test.summary()
# Compare p-value distribution under null model against uniform distribution.
pval_h0 = stats.kstest(test.pval, 'uniform').pvalue
logging.getLogger("diffxpy").info(
'KS-test pvalue for null model match of wald(): %f' % pval_h0)
assert pval_h0 > 0.05, "KS-Test failed: pval_h0 is <= 0.05!"
return True
def _prepare_data(self, n_cells: int = 2000, n_genes: int = 100):
"""
:param n_cells: Number of cells to simulate (number of observations per test).
:param n_genes: Number of genes to simulate (number of tests).
"""
num_non_de = n_genes // 2
sim = Simulator(num_observations=n_cells, num_features=n_genes)
sim.generate_sample_description(num_batches=0, num_conditions=2)
sim.generate_params(
rand_fn_ave=lambda shape: np.random.poisson(500, shape) + 1,
rand_fn=lambda shape: np.abs(np.random.uniform(1, 0.5, shape)))
sim.params["a_var"][1, :num_non_de] = 0
sim.params["b_var"][1, :num_non_de] = 0
sim.params["isDE"] = ("features", ), np.arange(n_genes) >= num_non_de
sim.generate_data()
return sim
def test_null_distribution_wald_multi(self, n_cells: int = 4000, n_genes: int = 200):
"""
Test if de.wald() (multivariate mode) generates a uniform p-value distribution
if it is given data simulated based on the null model. Returns the p-value
of the two-side Kolmgorov-Smirnov test for equality of the observed
p-value distribution and a uniform distribution.
:param n_cells: Number of cells to simulate (number of observations per test).
:param n_genes: Number of genes to simulate (number of tests).
"""
logging.getLogger("tensorflow").setLevel(logging.ERROR)
logging.getLogger("batchglm").setLevel(logging.WARNING)
logging.getLogger("diffxpy").setLevel(logging.WARNING)
sim = Simulator(num_observations=n_cells, num_features=n_genes)
sim.generate_sample_description(num_batches=0, num_conditions=2)
sim.generate()
sample_description = pd.DataFrame({
"covar1": np.random.randint(4, size=sim.nobs),
"covar2": np.random.randint(2, size=sim.nobs)
})
sample_description["cond"] = sim.sample_description["condition"].values
partition = de.test.partition(
data=sim.x,
parts="cond",
sample_description=sample_description
)
det = partition.wald(
factor_loc_totest="covar1",
formula_loc="~ 1 + covar1 + covar2",
training_strategy="DEFAULT",
dtype="float64"
)
_ = det.summary()
# Compare p-value distribution under null model against uniform distribution.
pval_h0 = stats.kstest(det.pval.flatten(), 'uniform').pvalue
logging.getLogger("diffxpy").info('KS-test pvalue for null model match of wald(): %f' % pval_h0)
assert pval_h0 > 0.05, "KS-Test failed: pval_h0=%f is <= 0.05!" % np.round(pval_h0, 5)
return True
def test_null_distribution_wilcoxon(self,
n_cells: int = 2000,
n_genes: int = 10000,
n_groups=2):
"""
Test if de.wald() generates a uniform p-value distribution
if it is given data simulated based on the null model. Returns the p-value
of the two-side Kolmgorov-Smirnov test for equality of the observed
p-value distriubution and a uniform distribution.
:param n_cells: Number of cells to simulate (number of observations per test).
:param n_genes: Number of genes to simulate (number of tests).
"""
logging.getLogger("tensorflow").setLevel(logging.ERROR)
logging.getLogger("batchglm").setLevel(logging.WARNING)
logging.getLogger("diffxpy").setLevel(logging.WARNING)
sim = Simulator(num_observations=n_cells, num_features=n_genes)
sim.generate_sample_description(num_batches=0, num_conditions=0)
sim.generate()
random_sample_description = pd.DataFrame({
"condition":
np.random.randint(n_groups, size=sim.num_observations)
})
test = de.test.pairwise(
data=sim.X,
grouping="condition",
test="wilcoxon",
sample_description=random_sample_description,
)
summary = test.summary()
# Compare p-value distribution under null model against uniform distribution.
pval_h0 = stats.kstest(
test.pval[~np.eye(test.pval.shape[0]).astype(bool)].flatten(),
'uniform').pvalue
logging.getLogger("diffxpy").info(
'KS-test pvalue for null model match of wald(): %f' % pval_h0)
assert pval_h0 > 0.05, "KS-Test failed: pval_h0 is <= 0.05!"
return True
def _test_null_distribution_wald_multi(self, n_cells: int, n_genes: int,
noise_model: str):
"""
Test if de.wald() (multivariate mode) generates a uniform p-value distribution
if it is given data simulated based on the null model. Returns the p-value
of the two-side Kolmgorov-Smirnov test for equality of the observed
p-value distribution and a uniform distribution.
:param n_cells: Number of cells to simulate (number of observations per test).
:param n_genes: Number of genes to simulate (number of tests).
:param noise_model: Noise model to use for data fitting.
"""
if noise_model == "nb":
from batchglm.api.models.glm_nb import Simulator
elif noise_model == "norm":
from batchglm.api.models.glm_norm import Simulator
else:
raise ValueError("noise model %s not recognized" % noise_model)
sim = Simulator(num_observations=n_cells, num_features=n_genes)
sim.generate_sample_description(num_batches=0, num_conditions=0)
sim.generate()
random_sample_description = pd.DataFrame(
{"condition": np.random.randint(4, size=sim.nobs)})
test = de.test.wald(data=sim.input_data,
sample_description=random_sample_description,
factor_loc_totest="condition",
formula_loc="~ 1 + condition",
noise_model=noise_model,
training_strategy="DEFAULT",
dtype="float64")
_ = test.summary()
# Compare p-value distribution under null model against uniform distribution.
pval_h0 = stats.kstest(test.pval, 'uniform').pvalue
logging.getLogger("diffxpy").info(
'KS-test pvalue for null model match of wald(): %f' % pval_h0)
assert pval_h0 > 0.05, ("KS-Test failed: pval_h0=%f is <= 0.05!" %
np.round(pval_h0, 5))
return True
def test_null_distribution_lrt(self,
n_cells: int = 2000,
n_genes: int = 100):
"""
Test if de.test_wald_loc() generates a uniform p-value distribution
if it is given data simulated based on the null model. Returns the p-value
of the two-side Kolmgorov-Smirnov test for equality of the observed
p-value distriubution and a uniform distribution.
:param n_cells: Number of cells to simulate (number of observations per test).
:param n_genes: Number of genes to simulate (number of tests).
"""
logging.getLogger("tensorflow").setLevel(logging.ERROR)
logging.getLogger("batchglm").setLevel(logging.WARNING)
logging.getLogger("diffxpy").setLevel(logging.WARNING)
sim = Simulator(num_observations=n_cells, num_features=n_genes)
sim.generate_sample_description(num_batches=0, num_conditions=0)
sim.generate()
random_sample_description = pd.DataFrame(
{"condition": np.random.randint(2, size=sim.num_observations)})
test = de.test.versus_rest(
data=sim.X,
grouping="condition",
test="lrt",
noise_model="nb",
sample_description=random_sample_description,
batch_size=500,
training_strategy="DEFAULT",
dtype="float64")
summary = test.summary()
# Compare p-value distribution under null model against uniform distribution.
pval_h0 = stats.kstest(test.pval.flatten(), 'uniform').pvalue
logging.getLogger("diffxpy").info(
'KS-test pvalue for null model match of test_wald_loc(): %f' %
pval_h0)
assert pval_h0 > 0.05, "KS-Test failed: pval_h0 is <= 0.05!"
return True
def simulate(self):
if self.noise_model is None:
raise ValueError("noise_model is None")
else:
if self.noise_model == "nb":
from batchglm.api.models.glm_nb import Simulator
elif self.noise_model == "norm":
from batchglm.api.models.glm_norm import Simulator
elif self.noise_model == "beta":
from batchglm.api.models.glm_beta import Simulator
else:
raise ValueError("noise_model not recognized")
num_observations = 500
sim = Simulator(num_observations=num_observations, num_features=4)
sim.generate_sample_description(num_conditions=2, num_batches=2)
sim.generate()
self.sim = sim
def test_null_distribution_z_lazy(self,
n_cells: int = 2000,
n_genes: int = 100):
"""
Test if de.pairwise() generates a uniform p-value distribution for lazy z-tests
if it is given data simulated based on the null model. Returns the p-value
of the two-side Kolmgorov-Smirnov test for equality of the observed
p-value distriubution and a uniform distribution.
:param n_cells: Number of cells to simulate (number of observations per test).
:param n_genes: Number of genes to simulate (number of tests).
"""
logging.getLogger("tensorflow").setLevel(logging.ERROR)
logging.getLogger("batchglm").setLevel(logging.WARNING)
logging.getLogger("diffxpy").setLevel(logging.WARNING)
sim = Simulator(num_observations=n_cells, num_features=n_genes)
sim.generate_sample_description(num_batches=0, num_conditions=0)
sim.generate()
random_sample_description = pd.DataFrame(
{"condition": np.random.randint(4, size=sim.num_observations)})
test = de.test.pairwise(data=sim.X,
grouping="condition",
test='z-test',
lazy=True,
noise_model="nb",
pval_correction="global",
quick_scale=True,
sample_description=random_sample_description,
dtype="float64")
# Compare p-value distribution under null model against uniform distribution.
pvals = test.pval_pairs(groups0=0, groups1=1)
pval_h0 = stats.kstest(pvals.flatten(), 'uniform').pvalue
logging.getLogger("diffxpy").info(
'KS-test pvalue for null model match of wald(): %f' % pval_h0)
assert pval_h0 > 0.05, "KS-Test failed: pval_h0 is <= 0.05!"
return True
def _test_model_fit_partition(self, n_cells: int, n_genes: int,
noise_model: str):
"""
Test if de.wald() generates a uniform p-value distribution
if it is given data simulated based on the null model. Returns the p-value
of the two-side Kolmgorov-Smirnov test for equality of the observed
p-value distribution and a uniform distribution.
:param n_cells: Number of cells to simulate (number of observations per test).
:param n_genes: Number of genes to simulate (number of tests).
:param noise_model: Noise model to use for data fitting.
"""
if noise_model == "nb":
from batchglm.api.models.glm_nb import Simulator
rand_fn_scale = lambda shape: np.random.uniform(1, 2, shape)
elif noise_model == "norm":
from batchglm.api.models.glm_norm import Simulator
rand_fn_scale = lambda shape: np.random.uniform(1, 2, shape)
else:
raise ValueError("noise model %s not recognized" % noise_model)
sim = Simulator(num_observations=n_cells, num_features=n_genes)
sim.generate_sample_description(num_batches=0, num_conditions=0)
sim.generate_params(rand_fn_scale=rand_fn_scale)
sim.generate_data()
random_sample_description = pd.DataFrame({
"condition":
np.random.randint(2, size=sim.nobs),
"batch":
np.random.randint(2, size=sim.nobs)
})
partition = de.fit.partition(
data=sim.input_data,
sample_description=random_sample_description,
parts="condition")
estim = partition.model(formula_loc="~ 1 + batch",
noise_model=noise_model)
return True
def test_sparse_anndata(self, n_cells: int = 2000, n_genes: int = 100):
"""
Test if de.wald() generates a uniform p-value distribution
if it is given data simulated based on the null model. Returns the p-value
of the two-side Kolmgorov-Smirnov test for equality of the observed
p-value distribution and a uniform distribution.
:param n_cells: Number of cells to simulate (number of observations per test).
:param n_genes: Number of genes to simulate (number of tests).
"""
logging.getLogger("tensorflow").setLevel(logging.ERROR)
logging.getLogger("batchglm").setLevel(logging.WARNING)
logging.getLogger("diffxpy").setLevel(logging.WARNING)
sim = Simulator(num_observations=n_cells, num_features=n_genes)
sim.generate_sample_description(num_batches=0, num_conditions=0)
sim.generate()
random_sample_description = pd.DataFrame(
{"condition": np.random.randint(2, size=sim.num_observations)})
adata = anndata.AnnData(scipy.sparse.csr_matrix(sim.X.values))
# X = adata.X
test = de.test.wald(data=adata,
factor_loc_totest="condition",
formula="~ 1 + condition",
sample_description=random_sample_description,
quick_scale=True,
training_strategy="DEFAULT",
dtype="float64")
summary = test.summary()
# Compare p-value distribution under null model against uniform distribution.
pval_h0 = stats.kstest(test.pval, 'uniform').pvalue
logging.getLogger("diffxpy").info(
'KS-test pvalue for null model match of wald(): %f' % pval_h0)
assert pval_h0 > 0.05, "KS-Test failed: pval_h0 is <= 0.05!"
return True
def test_forfatal_from_dict(self):
"""
Test if dictionary-based constraint interface is working.
"""
logging.getLogger("tensorflow").setLevel(logging.ERROR)
logging.getLogger("batchglm").setLevel(logging.WARNING)
logging.getLogger("diffxpy").setLevel(logging.WARNING)
n_cells = 2000
n_genes = 2
sim = Simulator(num_observations=n_cells, num_features=n_genes)
sim.generate_sample_description(num_batches=0, num_conditions=0)
sim.generate()
# Build design matrix:
sample_description = pd.DataFrame({
"cond": ["cond" + str(i // 1000) for i in range(n_cells)],
"batch": ["batch" + str(i // 500) for i in range(n_cells)]
})
# Build constraints:
dmat_loc, constraints_loc = de.utils.constraint_matrix_from_dict(
sample_description=sample_description,
formula="~1+cond+batch",
constraints={"batch": "cond"},
dims=["design_loc_params", "loc_params"])
dmat_scale, constraints_scale = de.utils.constraint_matrix_from_dict(
sample_description=sample_description,
formula="~1+cond+batch",
constraints={"batch": "cond"},
dims=["design_scale_params", "scale_params"])
test = de.test.wald(data=sim.x,
dmat_loc=dmat_loc,
dmat_scale=dmat_scale,
constraints_loc=constraints_loc,
constraints_scale=constraints_scale,
coef_to_test=["cond[T.cond1]"])
_ = test.summary()
def _prepate_data(self, n_cells: int, n_genes: int, n_groups: int):
if self.noise_model == "nb":
from batchglm.api.models.glm_nb import Simulator
rand_fn_loc = lambda shape: np.random.uniform(0.1, 1, shape)
rand_fn_scale = lambda shape: np.random.uniform(0.5, 1, shape)
elif self.noise_model == "norm" or self.noise_model is None:
from batchglm.api.models.glm_norm import Simulator
rand_fn_loc = lambda shape: np.random.uniform(500, 1000, shape)
rand_fn_scale = lambda shape: np.random.uniform(1, 2, shape)
else:
raise ValueError("noise model %s not recognized" %
self.noise_model)
sim = Simulator(num_observations=n_cells, num_features=n_genes)
sim.generate_sample_description(num_batches=0, num_conditions=0)
sim.generate_params(rand_fn_loc=rand_fn_loc,
rand_fn_scale=rand_fn_scale)
sim.generate_data()
random_sample_description = pd.DataFrame(
{"condition": np.random.randint(n_groups, size=sim.nobs)})
return sim, random_sample_description
def test_for_fatal(self):
"""
"""
logging.getLogger("tensorflow").setLevel(logging.ERROR)
logging.getLogger("batchglm").setLevel(logging.WARNING)
logging.getLogger("diffxpy").setLevel(logging.WARNING)
sim = Simulator(num_observations=50, num_features=10)
sim.generate_sample_description(num_batches=0, num_conditions=2)
sim.generate()
test = de.test.wald(data=sim.X,
factor_loc_totest="condition",
formula_loc="~ 1 + condition",
sample_description=sim.sample_description,
gene_names=[str(x) for x in range(sim.X.shape[1])],
training_strategy="DEFAULT",
dtype="float64")
# Set up reference gene sets.
rs = de.enrich.RefSets()
rs.add(id="set1", source="manual", gene_ids=["1", "3"])
rs.add(id="set2", source="manual", gene_ids=["5", "6"])
for i in [True, False]:
for j in [True, False]:
enrich_test_i = de.enrich.test(
ref=rs,
det=test,
threshold=0.05,
incl_all_zero=i,
clean_ref=j,
)
_ = enrich_test_i.summary()
_ = enrich_test_i.significant_set_ids()
_ = enrich_test_i.significant_sets()
_ = enrich_test_i.set_summary(id="set1")
return True
def test_t_test_zero_variance(self,
n_cells: int = 2000,
n_genes: int = 100):
"""
Test if de.t_test() generates a uniform p-value distribution
if it is given data simulated based on the null model. Returns the p-value
of the two-side Kolmgorov-Smirnov test for equality of the observed
p-value distribution and a uniform distribution.
:param n_cells: Number of cells to simulate (number of observations per test).
:param n_genes: Number of genes to simulate (number of tests).
"""
logging.getLogger("tensorflow").setLevel(logging.ERROR)
logging.getLogger("batchglm").setLevel(logging.WARNING)
logging.getLogger("diffxpy").setLevel(logging.WARNING)
sim = Simulator(num_observations=n_cells, num_features=n_genes)
sim.generate_sample_description(num_batches=0, num_conditions=0)
sim.generate()
sim.data.X[:, 0] = np.exp(sim.a)[0, 0]
random_sample_description = pd.DataFrame(
{"condition": np.random.randint(2, size=sim.num_observations)})
test = de.test.t_test(data=sim.X,
grouping="condition",
sample_description=random_sample_description)
# Compare p-value distribution under null model against uniform distribution.
pval_h0 = stats.kstest(test.pval, 'uniform').pvalue
print('KS-test pvalue for null model match of t_test(): %f' % pval_h0)
assert pval_h0 > 0.05, "KS-Test failed: pval_h0 is <= 0.05!"
return pval_h0
def _test_compute_hessians(self):
if self.noise_model is None:
raise ValueError("noise_model is None")
else:
if self.noise_model == "nb":
from batchglm.api.models.glm_nb import Simulator, InputData
else:
raise ValueError("noise_model not recognized")
num_observations = 500
num_conditions = 2
sim = Simulator(num_observations=num_observations, num_features=4)
sim.generate_sample_description(num_conditions=num_conditions,
num_batches=2)
sim.generate()
sample_description = data_utils.sample_description_from_xarray(
sim.data, dim="observations")
design_loc = data_utils.design_matrix(
sample_description, formula="~ 1 + condition + batch")
design_scale = data_utils.design_matrix(sample_description,
formula="~ 1 + condition")
input_data = InputData.new(sim.X,
design_loc=design_loc,
design_scale=design_scale)
logger.debug("* Running analytic Hessian by observation tests")
pkg_constants.HESSIAN_MODE = "obs_batched"
self.estimator_ob = self.estimate(input_data)
t0_ob = time.time()
self.H_ob = self.estimator_ob.hessians
t1_ob = time.time()
self.estimator_ob.close_session()
self.t_ob = t1_ob - t0_ob
logger.debug("* Running analytic Hessian by feature tests")
pkg_constants.HESSIAN_MODE = "feature"
self.estimator_fw = self.estimate(input_data)
t0_fw = time.time()
self.H_fw = self.estimator_fw.hessians
t1_fw = time.time()
self.estimator_fw.close_session()
self.t_fw = t1_fw - t0_fw
logger.debug("* Running tensorflow Hessian by feature tests")
pkg_constants.HESSIAN_MODE = "tf"
self.estimator_tf = self.estimate(input_data)
t0_tf = time.time()
# tensorflow computes the negative hessian as the
# objective is the negative log-likelihood.
self.H_tf = self.estimator_tf.hessians
t1_tf = time.time()
self.estimator_tf.close_session()
self.t_tf = t1_tf - t0_tf
i = 1
logger.info("run time observation batch-wise analytic solution: %f" %
self.t_ob)
logger.info("run time feature-wise analytic solution: %f" % self.t_fw)
logger.info("run time feature-wise tensorflow solution: %f" %
self.t_tf)
logger.info(
"ratio of tensorflow feature-wise hessian to analytic observation batch-wise hessian:"
)
logger.info(self.H_tf.values[i, :, :] / self.H_ob.values[i, :, :])
logger.info(
"ratio of tensorflow feature-wise hessian to analytic feature-wise hessian:"
)
logger.info(self.H_tf.values[i, :, :] / self.H_fw.values[i, :, :])
max_rel_dev1 = np.max(
np.abs((self.H_tf.values - self.H_ob.values) / self.H_tf.values))
max_rel_dev2 = np.max(
np.abs((self.H_tf.values - self.H_fw.values) / self.H_tf.values))
assert max_rel_dev1 < 1e-10
assert max_rel_dev2 < 1e-10
return True
def test_null_distribution_wald_constrained_2layer(self,
n_genes: int = 100):
"""
Test if de.wald() with constraints generates a uniform p-value distribution
if it is given data simulated based on the null model. Returns the p-value
of the two-side Kolmgorov-Smirnov test for equality of the observed
p-value distribution and a uniform distribution.
n_cells is constant as the design matrix and constraints depend on it.
:param n_genes: Number of genes to simulate (number of tests).
"""
logging.getLogger("tensorflow").setLevel(logging.ERROR)
logging.getLogger("batchglm").setLevel(logging.WARNING)
logging.getLogger("diffxpy").setLevel(logging.WARNING)
n_cells = 12000
sim = Simulator(num_observations=n_cells, num_features=n_genes)
sim.generate_sample_description(num_batches=0, num_conditions=0)
sim.generate()
# Build design matrix:
dmat = np.zeros([n_cells, 14])
dmat[:, 0] = 1
dmat[6000:12000, 1] = 1 # condition effect
dmat[:1000, 2] = 1 # bio rep 1 - treated 1
dmat[1000:3000, 3] = 1 # bio rep 2 - treated 2
dmat[3000:5000, 4] = 1 # bio rep 3 - treated 3
dmat[5000:6000, 5] = 1 # bio rep 4 - treated 4
dmat[6000:7000, 6] = 1 # bio rep 5 - untreated 1
dmat[7000:9000, 7] = 1 # bio rep 6 - untreated 2
dmat[9000:11000, 8] = 1 # bio rep 7 - untreated 3
dmat[11000:12000, 9] = 1 # bio rep 8 - untreated 4
dmat[1000:2000, 10] = 1 # tech rep 1
dmat[7000:8000, 10] = 1 # tech rep 1
dmat[2000:3000, 11] = 1 # tech rep 2
dmat[8000:9000, 11] = 1 # tech rep 2
dmat[3000:4000, 12] = 1 # tech rep 3
dmat[9000:10000, 12] = 1 # tech rep 3
dmat[4000:5000, 13] = 1 # tech rep 4
dmat[10000:11000, 13] = 1 # tech rep 4
coefficient_names = [
'intercept', 'treatment1', 'bio1', 'bio2', 'bio3', 'bio4', 'bio5',
'bio6', 'bio7', 'bio8', 'tech1', 'tech2', 'tech3', 'tech4'
]
dmat_est = pd.DataFrame(data=dmat, columns=coefficient_names)
dmat_est_loc = de.test.design_matrix(dmat=dmat_est)
dmat_est_scale = de.test.design_matrix(dmat=dmat_est.iloc[:, [0]])
# Build constraints:
constraints_loc = de.utils.data_utils.build_equality_constraints_string(
dmat=dmat_est_loc,
constraints=[
"bio1+bio2=0", "bio3+bio4=0", "bio5+bio6=0", "bio7+bio8=0",
"tech1+tech2=0", "tech3+tech4=0"
],
dims=["design_loc_params", "loc_params"])
constraints_scale = None
test = de.test.wald(data=sim.X,
dmat_loc=dmat_est_loc.data_vars['design'],
dmat_scale=dmat_est_scale.data_vars['design'],
init_a="standard",
init_b="standard",
constraints_loc=constraints_loc,
constraints_scale=constraints_scale,
coef_to_test=["treatment1"],
training_strategy="DEFAULT",
quick_scale=False,
dtype="float64")
summary = test.summary()
# Compare p-value distribution under null model against uniform distribution.
pval_h0 = stats.kstest(test.pval, 'uniform').pvalue
logging.getLogger("diffxpy").info(
'KS-test pvalue for null model match of wald(): %f' % pval_h0)
assert pval_h0 > 0.05, "KS-Test failed: pval_h0 is <= 0.05!"
return True
def test_null_distribution_wald_multi_constrained_2layer(
self, n_genes: int = 50):
"""
Test if de.wald() for multiple coefficients with constraints
generates a uniform p-value distribution
if it is given data simulated based on the null model. Returns the p-value
of the two-side Kolmgorov-Smirnov test for equality of the observed
p-value distribution and a uniform distribution.
n_cells is constant as the design matrix and constraints depend on it.
:param n_genes: Number of genes to simulate (number of tests).
"""
logging.getLogger("tensorflow").setLevel(logging.ERROR)
logging.getLogger("batchglm").setLevel(logging.WARNING)
logging.getLogger("diffxpy").setLevel(logging.WARNING)
n_cells = 3000
sim = Simulator(num_observations=n_cells, num_features=n_genes)
sim.generate_sample_description(num_batches=0, num_conditions=0)
sim.generate()
# Build design matrix:
dmat = np.zeros([n_cells, 9])
dmat[:, 0] = 1
dmat[:500, 1] = 1 # bio rep 1
dmat[500:1000, 2] = 1 # bio rep 2
dmat[1000:1500, 3] = 1 # bio rep 3
dmat[1500:2000, 4] = 1 # bio rep 4
dmat[2000:2500, 5] = 1 # bio rep 5
dmat[2500:3000, 6] = 1 # bio rep 6
dmat[1000:2000, 7] = 1 # condition effect 1
dmat[2000:3000, 8] = 1 # condition effect 2
coefficient_names = [
'intercept', 'bio1', 'bio2', 'bio3', 'bio4', 'bio5', 'bio6',
'treatment1', 'treatment2'
]
dmat_est = pd.DataFrame(data=dmat, columns=coefficient_names)
dmat_est_loc = de.utils.design_matrix(dmat=dmat_est)
dmat_est_scale = de.utils.design_matrix(dmat=dmat_est)
# Build constraints:
constraints_loc = de.utils.constraint_matrix_from_string(
dmat=dmat_est_loc,
constraints=["bio1+bio2=0", "bio3+bio4=0", "bio5+bio6=0"])
constraints_scale = de.utils.constraint_matrix_from_string(
dmat=dmat_est_scale,
constraints=["bio1+bio2=0", "bio3+bio4=0", "bio5+bio6=0"])
test = de.test.wald(data=sim.x,
dmat_loc=dmat_est_loc,
dmat_scale=dmat_est_scale,
constraints_loc=constraints_loc,
constraints_scale=constraints_scale,
coef_to_test=["treatment1", "treatment2"])
_ = test.summary()
# Compare p-value distribution under null model against uniform distribution.
pval_h0 = stats.kstest(test.pval, 'uniform').pvalue
logging.getLogger("diffxpy").info(
'KS-test pvalue for null model match of wald(): %f' % pval_h0)
assert pval_h0 > 0.05, "KS-Test failed: pval_h0=%f is <= 0.05!" % pval_h0
return True