def fit_cv(X,
y,
nepochs=100,
batch_size=10,
val_pct=0.1,
verbose=False,
lr=3e-4,
weight_decay=0.01,
model_type='nonlinear',
nfolds=5):
folds = create_folds(X, nfolds)
models = []
for fold_idx, fold in enumerate(folds):
print('Fitting model {}'.format(fold_idx))
mask = np.ones(X.shape[0], dtype=bool)
mask[fold] = False
models.append(
fit_nn(X[mask],
y[mask],
nepochs=nepochs,
batch_size=batch_size,
val_pct=val_pct,
verbose=verbose,
lr=lr,
weight_decay=weight_decay,
model_type=model_type))
return NeuralCvModel(models, folds)
def load_plx4720(verbose=False, feature_type="mutation"):
drug_target = "PLX4720"
if verbose:
print("Loading data")
X_drugs, y_drugs, drugs, cells, features = load_ccle(
feature_type=feature_type, drug_target=drug_target, normalize=True
)
drug_idx = drugs.get_loc(drug_target)
if verbose:
print("Drug {}".format(drugs[drug_idx]))
X_drug, y_drug = X_drugs[drug_idx], y_drugs[drug_idx]
######## Specific to PLX4720. Filters out all features with pearson correlation less than 0.1 in magnitude ########
ccle_expected_features = [
"C11orf85",
"FXYD4",
"SLC28A2",
"MAML3_MUT",
"RAD51L1_MUT",
"GAPDHS",
"BRAF_MUT",
]
if verbose:
print("Filtering by correlation with signal first")
ccle_selected, corrs = ccle_feature_filter(X_drug, y_drug)
for plx4720_feat in [f for f in ccle_expected_features if f in features]:
idx = features.get_loc(plx4720_feat)
ccle_selected[idx] = True
if verbose:
print("Correlation for {}: {:.4f}".format(plx4720_feat, corrs[idx]))
ccle_features = features[ccle_selected]
# Split the data into 10 folds where each fold contains at least 1 observation of each drug
nfolds = 10
drug_folds = [create_folds(x_i, nfolds) for x_i in X_drugs]
X_drug, y_drug, folds = X_drugs[drug_idx], y_drugs[drug_idx], drug_folds[drug_idx]
# Load or fit the model
MODEL_PATH = "data/model.pt"
if os.path.exists(MODEL_PATH):
elastic_model = torch.load(MODEL_PATH)
else:
elastic_model = CvModel(
fit_cv(X_drug, y_drug, folds, fit_elastic_net_ccle, selected=ccle_selected),
folds,
"Elastic Net",
selected=ccle_selected,
)
torch.save(elastic_model, MODEL_PATH)
# Plot the fit to show it's pretty good
# plot_ccle_predictions(elastic_model, X_drug, y_drug)
# Show the features selected by the heuristic if we fit this way (may be slightly different than in the paper)
if verbose:
print_top_features(elastic_model, ccle_expected_features)
return X_drug, y_drug, features, ccle_features, elastic_model
def load_or_fit_model(descriptor, X, Y):
nfolds = 10
y = Y[descriptor]
y = y[y.notnull()]
x = X.loc[y.index].values
y = y.values
model_path = 'data/{}.pt'.format(descriptor)
if os.path.exists(model_path):
forest_model = joblib.load(model_path)
else:
print('Fitting {}'.format(descriptor))
folds = create_folds(x, nfolds)
if descriptor == 'Intensity':
forest_model = CvModel(fit_cv(x, y, folds, fit_extratrees), folds,
'ExtraTrees')
else:
forest_model = CvModel(fit_cv(x, y, folds, fit_forest), folds,
'RandomForest')
plot_predictions(forest_model, x, y, descriptor)
joblib.dump(forest_model, model_path)
return x, y, forest_model
def calibrate_discrete(
X,
feature,
X_test=None,
nquantiles=101,
nbootstraps=100,
nfolds=5,
tv_threshold=0.005,
p_threshold=0.0,
use_cv=False,
):
"""Calibrates a bootstrap confidence interval conditional model for a given feature."""
classes = np.unique(X[:, feature])
nclasses = len(classes)
# Search over a linear quantile grid to search
quantile_range = np.linspace(0, 100, nquantiles)
jmask = np.ones(X.shape[1], dtype=bool)
jmask[feature] = False
if X_test is None and use_cv:
# Use k-fold cross-validation to generate conditional probability estimates for X_j
print("Fitting using {} bootstrap resamples and {} folds".format(
nbootstraps, nfolds))
probs = np.zeros((nquantiles, X.shape[0], nclasses))
proposals = []
folds = create_folds(X, nfolds)
for fold_idx, fold in enumerate(folds):
print(fold_idx)
imask = np.ones(X.shape[0], dtype=bool)
imask[fold] = False
model = DiscreteBootstrapConditionalModel(
X[imask][:, jmask],
X[imask][:, feature],
fit_classifier,
nbootstraps=nbootstraps,
)
# probs[:,fold] = model.pmf_quantiles(X[fold][:,jmask], X[fold][:,feature], quantile_range, axis=0)
for c in classes:
probs[:, fold, c] = model.pmf_quantiles(X[fold][:, jmask],
c,
quantile_range,
axis=0)
proposals.append(model)
# sampler = lambda l, u: sample_cv(X[:,jmask], proposals, folds, l, u)
sampler = CrossValidationSampler(X[:, jmask], proposals, folds)
outcomes = np.array([(X[:, feature] == c).mean() for c in classes])
else:
if X_test is None:
print("Using training set as testing set.")
X_test = X
# Use a held-out test set
print(
"Fitting using {} bootstrap resamples and a {}/{} train/test split"
.format(nbootstraps, X.shape[0], X_test.shape[0]))
model = DiscreteBootstrapConditionalModel(X[:, jmask],
X[:, feature],
fit_classifier,
nbootstraps=nbootstraps)
probs = np.zeros((nquantiles, X_test.shape[0], nclasses))
for cidx, c in enumerate(classes):
probs[:, :, cidx] = model.pmf_quantiles(X_test[:, jmask],
c,
quantile_range,
axis=0)
# sampler = lambda l, u: sample_holdout(X_test[:,jmask], model, l, u)
sampler = HoldoutSampler(X_test[:, jmask], model)
outcomes = np.array([(X_test[:, feature] == c).mean()
for c in classes])
# Find the lower quantile that forms a sufficient lower bound on the observed probabilities
for i in range(1, nquantiles // 2):
lower = quantile_range[nquantiles // 2 - i]
qlower = probs[nquantiles // 2 - i]
tv_lower = (qlower.mean(axis=0) - outcomes).clip(0, np.inf).sum()
tv_pvalue = tv_test(tv_lower, outcomes, probs.shape[1])
# print('Lower: {} TV: {} p: {}'.format(lower, tv_lower, tv_pvalue))
# Allow some error tolerance due to noise/finite data
if tv_lower <= tv_threshold or tv_pvalue <= p_threshold:
break
# Find the upper quantile
for i in range(1, nquantiles // 2):
upper = quantile_range[nquantiles // 2 + i]
qupper = probs[nquantiles // 2 + i]
tv_upper = (outcomes - qupper.mean(axis=0)).clip(0, np.inf).sum()
tv_pvalue = tv_test(tv_upper, outcomes, probs.shape[1])
# print('Upper: {} TV: {} p: {}'.format(upper, tv_upper, tv_pvalue))
# Allow some error tolerance due to noise/finite data
if tv_upper <= tv_threshold or tv_pvalue <= p_threshold:
break
# Our TV-distance is the worst-case of the two bounds
tv_stat = np.max([tv_lower, tv_upper])
sampler.quantiles = np.array([lower, upper])
# TODO: how do we get a p-value estimate here? no clear notion of null...
print("Selected intervals: [{},{}]".format(lower, upper))
return {
"model": model,
"probs": probs,
"tv_stat": tv_stat,
"upper": upper,
"lower": lower,
"qupper": qupper,
"qlower": qlower,
"quantiles": quantile_range,
"sampler": sampler,
}
def calibrate_continuous(X, feature,
X_test=None, nquantiles=101, nbootstraps=100,
nfolds=5, ks_threshold=0.005, p_threshold=0.,
use_cv=False):
'''Calibrates a bootstrap confidence interval conditional model for a given feature.'''
# Search over a linear quantile grid to search
quantile_range = np.linspace(0, 100, nquantiles)
jmask = np.ones(X.shape[1], dtype=bool)
jmask[feature] = False
if X_test is None and use_cv:
# Use k-fold cross-validation to generate conditional density estimates for X_j
print('Fitting using {} bootstrap resamples and {} folds'.format(nbootstraps, nfolds))
cdfs = np.zeros((nquantiles, X.shape[0]))
proposals = []
folds = create_folds(X, nfolds)
for fold_idx, fold in enumerate(folds):
imask = np.ones(X.shape[0], dtype=bool)
imask[fold] = False
model = BootstrapConditionalModel(X[imask][:,jmask], X[imask][:,feature], fit_mdn, nbootstraps=nbootstraps)
cdfs[:,fold] = model.cdf_quantiles(X[fold][:,jmask], X[fold][:,feature], quantile_range, axis=0)
proposals.append(model)
sampler = CrossValidationSampler(X[:,jmask], proposals, folds)
else:
if X_test is None:
print('Using training set as testing set.')
X_test = X
# Use a held-out test set
print('Fitting using {} bootstrap resamples and a {}/{} train/test split'.format(nbootstraps, X.shape[0], X_test.shape[0]))
model = BootstrapConditionalModel(X[:,jmask], X[:,feature], fit_mdn, nbootstraps=nbootstraps)
cdfs = model.cdf_quantiles(X_test[:,jmask], X_test[:,feature], quantile_range, axis=0)
sampler = HoldoutSampler(X_test[:,jmask], model)
# Look at the bounds of the CDF along a discrete grid of points
ks_grid = np.linspace(1e-6,1-1e-6,1001)
# Find the lower quantile that forms a sufficient upper bound on the uniform CDF
for i in range(1,nquantiles//2):
lower = quantile_range[nquantiles//2 - i]
qlower = cdfs[nquantiles//2 - i]
# U(0,1) CDF is the (0,1),(0,1) line. So at every point q on the grid of
# CDF points, we expect a well-calibrated model to have q*N points with
# CDF value lower than q. Here we are looking for an upper bound, so
# we measure the KS distance as the maximum amount the U(0,1) CDF is
# above the predicted CDF.
ks_lower = 0
for ks_point in ks_grid:
ks_lower = max(ks_lower, ks_point - (qlower <= ks_point).mean())
ks_pvalue = ks_test(ks_lower, cdfs.shape[1])
# print('Lower: {} KS: {} p: {}'.format(lower, ks_lower, ks_pvalue))
# Allow some error tolerance due to noise/finite data
if ks_lower <= ks_threshold or ks_pvalue <= p_threshold:
break
# Find the upper quantile
for i in range(1,nquantiles//2):
upper = quantile_range[nquantiles//2+i]
qupper = cdfs[nquantiles//2 + i]
# U(0,1) CDF is the (0,1),(0,1) line. So at every point q on the grid of
# CDF points, we expect a well-calibrated model to have q*N points with
# CDF value lower than q. Here we are looking for a lower bound, so
# we measure the KS distance as the maximum amount the U(0,1) CDF is
# below the predicted CDF.
ks_upper = 0
for ks_point in ks_grid:
ks_upper = max(ks_upper, (qupper <= ks_point).mean() - ks_point)
ks_pvalue = ks_test(ks_upper, cdfs.shape[1])
# print('Upper: {} KS: {} p: {}'.format(upper, ks_upper, ks_pvalue))
# Allow some error tolerance due to noise/finite data
if ks_upper <= ks_threshold or ks_pvalue <= p_threshold:
break
# Set the sampler to the chosen regions
sampler.quantiles = np.array([lower, upper])
# Our KS-distance is the worst-case of the two bounds
ks_stat = np.max([ks_lower, ks_upper])
# The p-value on the KS test that the bounded distribution is different
# from the Uniform distribution
ks_pvalue = ks_test(ks_stat, cdfs.shape[1])
print('Selected intervals: [{},{}]'.format(lower, upper))
return {'model': model,
'cdfs': cdfs,
'ks_stat': ks_stat,
'ks_pvalue': ks_pvalue,
'upper': upper,
'lower': lower,
'qupper': qupper,
'qlower': qlower,
'quantiles': quantile_range,
'sampler': sampler
}
def run(trial, feature, reset=False):
N = 500 # total number of samples
P = 500 # number of features
S = 40 # number of signal features
nperms = 5000
fdr_threshold = 0.1
nfolds = 5
X, y, truth = load_or_create_dataset(trial, N, P, S)
np.random.seed(trial * P + feature)
infos = [
ModelInfo(trial, "Partial Least Squares", fit_pls, "pls"),
ModelInfo(trial, "Lasso", fit_lasso_cv, "lasso"),
ModelInfo(trial, "Elastic Net", fit_elastic_net_cv, "enet"),
ModelInfo(trial, "Bayesian Ridge", fit_bridge, "bridge"),
ModelInfo(trial, "Polynomial Kernel Ridge", fit_kridge, "kridge"),
ModelInfo(trial, "RBF Support Vector", fit_svr, "svr"),
ModelInfo(trial, "Random Forest", fit_forest, "rf")
# ModelInfo(trial, 'Extra Trees', fit_extratrees, 'xtrees')
]
folds = get_model(infos[0], X, y, create_folds(X, nfolds), reset).folds
models = [get_model(info, X, y, folds, reset) for info in infos]
# Create the test statistic for each model
# tstats = [(lambda X_target: ((y - model.predict(X_target))**2).mean()) for model in models]
# Load the conditional model for this feature
conditional = get_conditional(trial, feature)
# Run the normal CVRT for the first model, but save the null samples to
# avoid recomputing them for the rest of the models.
info, model = infos[0], models[0]
tstat = lambda X_target: ((y - model.predict(X_target))**2).mean()
print("Running CVRT for {}".format(info.name))
results = hrt(
feature,
tstat,
X,
nperms=nperms,
conditional=conditional,
lower=conditional.quantiles[0],
upper=conditional.quantiles[1],
save_nulls=True,
)
p_value = results["p_value"]
print("p={}".format(p_value))
np.save("data/{}/{}_{}.npy".format(trial, info.prefix, feature), p_value)
# Get the relevant values from the full CVRT on the first model
t_true = results["t_stat"]
X_nulls = results["samples_null"]
quantile_nulls = results["quantiles_null"]
# Run the CVRTs for the remaining models using the same null samples
X_null = np.copy(X)
for info, model in zip(infos[1:], models[1:]):
print("Running cached CVRT for {}".format(info.name))
t_weights = np.full(nperms, np.nan)
t_null = np.full(nperms, np.nan)
tstat = lambda X_target: ((y - model.predict(X_target))**2).mean()
t_true = tstat(X)
for perm in range(nperms):
if (perm % 500) == 0:
print("Trial {}".format(perm))
# Get the test-statistic under the null
X_null[:, feature] = X_nulls[perm]
t_null[perm] = tstat(X_null)
if t_null[perm] <= t_true:
# Over-estimate the likelihood
t_weights[perm] = quantile_nulls[perm, 1]
else:
# Under-estimate the likelihood
t_weights[perm] = quantile_nulls[perm, 0]
p_value = t_weights[t_null <= t_true].sum() / t_weights.sum()
print("p={}".format(p_value))
np.save("data/{}/{}_{}.npy".format(trial, info.prefix, feature),
p_value)