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ccle_data.py
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ccle_data.py
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import numpy as np
import pandas as pd
import matplotlib.pyplot as plt
'''
This code reproduces the real data experiments using the CCLE data.
Preprocessing steps follow the code of W. Tansey at https://github.com/tansey/hrt.
And the following code is obtained from https://github.com/alexisbellot/GCIT.
'''
def load_ccle(drug_target='PLX4720', feature_type='both', normalize=False):
'''
:param drug target: specific drug we w ant to analyse
:param normalize: normalize data
:return: genetic features (mutations) as a 2d array for each cancer cell and corresponding drug response measured with Amax
'''
if feature_type in ['expression', 'both']:
# Load gene expression
expression = pd.read_csv('./ccle_data/expression.txt', delimiter='\t', header=2, index_col=1).iloc[:, 1:]
expression.columns = [c.split(' (ACH')[0] for c in expression.columns]
features = expression
if feature_type in ['mutation', 'both']:
# Load gene mutation
mutations = pd.read_csv('./ccle_data/mutation.txt', delimiter='\t', header=2, index_col=1).iloc[:,1:]
mutations = mutations.iloc[[c.endswith('_MUT') for c in mutations.index]]
features = mutations
if feature_type == 'both':
# get cells having both expression and mutation data
both_cells = set(expression.columns) & set(mutations.columns)
z = {}
for c in both_cells:
exp = expression[c].values
if len(exp.shape) > 1:
exp = exp[:, 0]
z[c] = np.concatenate([exp, mutations[c].values])
both_df = pd.DataFrame(z, index=[c for c in expression.index] + [c for c in mutations.index])
features = both_df
print('Genetic features dimension = {} on {} cancer cells'.format(features.shape[0], features.shape[1]))
# Get per-drug X and y regression targets
response = pd.read_csv('./ccle_data/response.csv', header=0, index_col=[0, 2])
# names of cell lines, there are 504
cells = response.index.levels[0]
# names of drugs, there are 24
drugs = response.index.levels[1]
X_drugs = [[] for _ in drugs]
y_drugs = [[] for _ in drugs]
# subset data to include only cells, mutations and response associated with chosen drug
for j, drug in enumerate(drugs):
if drug_target is not None and drug != drug_target:
continue # return to beginning of the loop
for i, cell in enumerate(cells):
if cell not in features.columns or (cell, drug) not in response.index:
continue
# all j empty except index that corresponds to target drug
# for this j we iteratively append all the mutations on every cell
X_drugs[j].append(features[cell].values) # store genetic features (mutations and expression) that appear in cells
y_drugs[j].append(response.loc[(cell, drug), 'Amax']) # store response of the drug
print('{}: Cell number = {}'.format(drug, len(y_drugs[j])))
# convert to np array
X_drugs = [np.array(x_i) for x_i in X_drugs]
y_drugs = [np.array(y_i) for y_i in y_drugs]
if normalize:
X_drugs = [(x_i if (len(x_i) == 0) else (x_i - x_i.min(axis=0, keepdims=True)) /
(x_i.max(axis=0, keepdims=True) - x_i.min(axis=0, keepdims=True)))
for x_i in X_drugs]
y_drugs = [(y_i if (len(y_i) == 0 or y_i.std() == 0) else (y_i - y_i.min(axis=0, keepdims=True)) /
(y_i.max(axis=0, keepdims=True) - y_i.min(axis=0, keepdims=True)))
for y_i in y_drugs]
'''
if normalize:
X_drugs = [(x_i if (len(x_i) == 0) else (x_i - x_i.mean(axis=0, keepdims=True)) /
x_i.std(axis=0).clip(1e-6)) for x_i in X_drugs]
y_drugs = [(y_i if (len(y_i) == 0 or y_i.std() == 0) else (y_i - y_i.mean()) / y_i.std()) for y_i in y_drugs]
'''
drug_idx = drugs.get_loc(drug_target)
# 2d array for features and 1d array for response
X_drug, y_drug = X_drugs[drug_idx], y_drugs[drug_idx]
return X_drug, y_drug, features
# X_drug, y_drug, features = load_ccle(feature_type='mutation')
def ccle_feature_filter(X, y, threshold=0.1):
'''
:param X: features
:param y: response
:param threshold: correlation threshold
:return: logical array with False for all features that do not have at least pearson correlation at threshold with y
and correlations for all variables
'''
corrs = np.array([np.abs(np.corrcoef(x, y)[0, 1]) if x.std() > 0 else 0 for x in X.T])
selected = corrs >= threshold # True/False
print(selected.sum(), selected.shape, corrs)
return selected, corrs
# ccle_selected, corrs = ccle_feature_filter(X_drug, y_drug, threshold=0.1)
# features.index[ccle_selected]
# stats.describe(corrs[ccle_selected])
def fit_elastic_net_ccle(X, y, nfolds=3):
'''
:param X: features
:param y: response
:param nfolds: number of folds for hyperparameter tuning
:return: fitted elastic net model
'''
from sklearn.linear_model import ElasticNetCV
# The parameter l1_ratio corresponds to alpha in the glmnet R package
# while alpha corresponds to the lambda parameter in glmnet
# enet = ElasticNetCV(l1_ratio=np.linspace(0.2, 1.0, 10),
# alphas=np.exp(np.linspace(-6, 5, 250)),
# cv=nfolds)
enet = ElasticNetCV(l1_ratio=0.2, # It always chooses l1_ratio=0.2
alphas=np.exp(np.linspace(-6, 5, 250)),
cv=nfolds)
print('Fitting via CV')
enet.fit(X, y)
alpha, l1_ratio = enet.alpha_, enet.l1_ratio_
print('Chose values: alpha={}, l1_ratio={}'.format(alpha, l1_ratio))
return enet
# elastic_model = fit_elastic_net_ccle(X_drug[:,ccle_selected], y_drug)
def fit_random_forest_ccle(X, y):
'''
:param X: features
:param y: response
:param nfolds: number of folds for hyperparameter tuning
:return: fitted elastic net model
'''
from sklearn.ensemble import RandomForestRegressor
rf = RandomForestRegressor()
rf.fit(X,y)
return rf
# rf_model = fit_random_forest_ccle(X_drug[:,ccle_selected], y_drug)
def plot_ccle_predictions(model, X, y):
from sklearn.metrics import r2_score
plt.close()
y_hat = model.predict(X)
plt.scatter(y_hat, y, color='blue')
plt.plot([min(y.min(), y_hat.min()), max(y.max(), y_hat.max())],
[min(y.min(), y_hat.min()),max(y.max(), y_hat.max())], color='red', lw=3)
plt.xlabel('Predicted')
plt.ylabel('Truth')
plt.title(' ($r^2$={:.4f})'.format( r2_score(y, y_hat)))
plt.tight_layout()
# plot_ccle_predictions(elastic_model,X_drug[:,ccle_selected],y_drug)
def print_top_features(model):
# model_weights = np.mean([m.coef_ for m in model.models], axis=0)
if model == rf_model:
model_weights = model.feature_importances_
else:
model_weights = model.coef_
ccle_features = features[ccle_selected]
print('Top by fit:')
for idx, top in enumerate(np.argsort(np.abs(model_weights))[::-1]):
print('{}. {}: {:.4f}'.format(idx+1, ccle_features.index[top], model_weights[top]))
# print_top_features(rf_model)
# print_top_features(elastic_model)
def run_test_ccle(X, Y):
pval = []
for x_index in range(X.shape[1]):
z = np.delete(X, x_index, axis=1)
x = X[:, x_index]
x = x.reshape((len(x), 1))
Y = Y.reshape((len(Y), 1))
# now run test
pval.append(GCIT(x, Y, z))
ccle_features = features[ccle_selected]
print('Top by fit:')
for idx, top in enumerate(np.argsort(np.abs(pval))):
print('{}. {}: {:.4f}'.format(idx+1, ccle_features.index[top], pval[top]))
# run_test_ccle(X_drug[:,ccle_selected],y_drug)