def pmid_26033813_analysis(drug: str):
tree = build_tree()
feature_label_path = find_newest_data_path(
f'compute_drug_features_labels_alpha_{args.alpha:.2f}')
labels_all = pd.read_pickle(feature_label_path / f'labels_{drug}.pickle')
selected_samples = sorted_intersection(labels_all.index, expr.index)
selected_labels = labels_all.loc[selected_samples]
selected_expr = expr.loc[selected_samples, :]
fit_tree(selected_expr, selected_labels, tree)
predictions = pd.Series(
[
predict_sample(sample_name, selected_expr, tree)
for sample_name in selected_samples
],
index=selected_samples,
)
rd = RocData.calculate(selected_labels, predictions)
rd.save(data_path / f'roc_data_{drug}.pickle')
plot_roc(rd, f'PMID26033813 ROC: {drug.title()}',
output_path / f'{drug}_roc.pdf')
pr = PrData.calculate(selected_labels, predictions)
plot_pr(pr, f'PMID26033813 Precision-Recall: {drug.title()}',
output_path / f'{drug}_pr.pdf')
def ki67_analysis(drug: str):
feature_label_path = find_newest_data_path(
f'compute_drug_features_labels_alpha_{args.alpha:.2f}')
labels_all = pd.read_pickle(feature_label_path / f'labels_{drug}.pickle')
selected_samples = sorted_intersection(labels_all.index, expr.index)
selected_expr = expr.loc[selected_samples, gene]
selected_labels = labels_all.loc[selected_samples]
rd = RocData.calculate(selected_labels, selected_expr)
rd.save(data_path / f'roc_data_{drug}.pickle')
plot_roc(rd, f'Ki67 ROC: {drug.title()}', output_path / f'{drug}_roc.pdf')
pr = PrData.calculate(selected_labels, selected_expr)
plot_pr(pr, f'Ki67 Precision-Recall: {drug.title()}',
output_path / f'{drug}_pr.pdf')
def propagate_data(data: pd.DataFrame, label: str):
"""
:param data: Matrix of (samples, genes); network propagation will be run on each row
:param label: mutations or diffexpr or something
:return:
"""
sample_count = len(data.index)
data_gene_set = set(data.columns)
common_genes = sorted_intersection(data.columns, node_set)
common_genes_path = data_path / f'{label}_common_genes.txt'
print(f'{label}: saving {len(common_genes)} common genes to {common_genes_path}')
with common_genes_path.open('w') as f:
for gene in common_genes:
print(gene, file=f)
only_mut_genes = sorted(data_gene_set - node_set)
only_mut_genes_path = data_path / f'{label}_only_mut_genes.txt'
print(f'{label}: saving {len(only_mut_genes)} data-only genes to {only_mut_genes_path}')
with only_mut_genes_path.open('w') as f:
for gene in only_mut_genes:
print(gene, file=f)
only_network_genes = sorted(node_set - data_gene_set)
only_network_genes_path = data_path / '{}_only_network_genes.txt'.format(label)
print(f'{label}: saving {len(only_network_genes)} network-only genes to {only_network_genes_path}')
with only_network_genes_path.open('w') as f:
for gene in only_network_genes:
print(gene, file=f)
data_network = pd.DataFrame(0.0, columns=nodes, index=data.index)
data_propagated = pd.DataFrame(0.0, columns=nodes, index=data.index)
data_network.loc[:, common_genes] = data.loc[:, common_genes]
param_generator = (
(i, sample, label, sample_count, data_network.loc[sample, :])
for i, sample in enumerate(data_network.index)
)
with Pool(args.subprocesses) as pool:
for sample, propagated in pool.imap_unordered(
propagate_mutations,
param_generator,
):
data_propagated.loc[sample, :] = np.array(propagated).reshape((node_count,))
return data_propagated
def pmid_26892682_analysis(drug: str):
feature_label_path = find_newest_data_path(
f'compute_drug_features_labels_alpha_{args.alpha:.2f}')
labels_all = pd.read_pickle(feature_label_path / f'labels_{drug}.pickle')
selected_samples = sorted_intersection(labels_all.index, expr.index)
selected_expr = expr.loc[selected_samples, selected_genes]
selected_labels = labels_all.loc[selected_samples]
ln_p_over_1_minus_p = selected_expr.as_matrix() @ coefs.as_matrix()
probs = expit(ln_p_over_1_minus_p)
rd = RocData.calculate(selected_labels, probs)
rd.save(data_path / f'roc_data_{drug}.pickle')
plot_roc(rd, f'PMID26892682 ROC: {drug.title()}',
output_path / f'{drug}_roc.pdf')
pr = PrData.calculate(selected_labels, probs)
plot_pr(pr, f'PMID26892682 Precision-Recall: {drug.title()}',
output_path / f'{drug}_pr.pdf')
output_path = create_output_path(script_label)
genes = [
'TWIST1', 'KRT81', 'PTRF', 'EEF1A2', 'PTPRK', 'EGFR', 'CXCL14', 'ERBB3'
]
t_value_strs = [
'-2.879', '-2.453', '-2.024', '-1.895', '-1.793', '-1.701', '2.229', '2.26'
]
t_values_inverted = np.array([float(v) for v in t_value_strs])
t_values = -t_values_inverted
coefs_all = pd.Series(t_values, index=genes)
expr_path = find_newest_data_path('parse_cosmic_diffexpr')
expr = pd.read_pickle(expr_path / 'brca_expr.pickle')
selected_genes = sorted_intersection(coefs_all.index, expr.columns)
coefs = coefs_all.loc[selected_genes]
def pmid_26892682_analysis(drug: str):
feature_label_path = find_newest_data_path(
f'compute_drug_features_labels_alpha_{args.alpha:.2f}')
labels_all = pd.read_pickle(feature_label_path / f'labels_{drug}.pickle')
selected_samples = sorted_intersection(labels_all.index, expr.index)
selected_expr = expr.loc[selected_samples, selected_genes]
selected_labels = labels_all.loc[selected_samples]
ln_p_over_1_minus_p = selected_expr.as_matrix() @ coefs.as_matrix()
probs = expit(ln_p_over_1_minus_p)
drugs = ['ai_all', 'arimidex']
feature_label_path = find_newest_data_path(
f'compute_drug_features_labels_alpha_{args.alpha:.2f}')
aucs = pd.Series(0, index=range(len(reordered_labels)))
for drug in drugs:
roc_data = []
for i, (order, clusters) in enumerate(reordered_labels):
labels_all = pd.read_pickle(feature_label_path /
f'labels_{drug}.pickle')
selected_samples = sorted_intersection(labels_all.index,
clusters.index)
selected_labels = labels_all.loc[selected_samples]
selected_clusters = clusters.loc[selected_samples]
rd = RocData.calculate(selected_labels, selected_clusters)
rd.save(data_path / f'roc_data_{drug}_permutation_{i}.pickle')
roc_data.append(rd)
aucs.loc[i] = rd.auc
with new_plot():
plt.figure(figsize=CROSSVAL_FIGSIZE)
for i, rd in enumerate(roc_data):
plt.plot(
rd.fpr,
rd.tpr,
dfs_to_consolidate.append((pca_feature_matrix, 'drug_mut_full'))
for drug in sorted(expr_full_pca):
pca_feature_matrix = expr_full_pca[drug]
dfs_to_consolidate.append((pca_feature_matrix, 'drug_expr_full'))
full_matrix_unscaled = consolidate_data_frames(dfs_to_consolidate).fillna(0)
full_matrix_unscaled_path = data_path / 'feature_matrix_unscaled.pickle'
print('Saving full matrix (unscaled) to', full_matrix_unscaled_path)
full_matrix_unscaled.to_pickle(full_matrix_unscaled_path)
data_desc_filepath = data_path / 'data_desc_unscaled.csv'
print('Saving unscaled data description to', data_desc_filepath)
full_matrix_unscaled.describe().T.to_csv(data_desc_filepath)
common_samples = sorted_intersection(full_matrix_unscaled.index,
tx_info_raw.index)
scaler, full_matrix = scale_continuous_df_cols(full_matrix_unscaled)
full_matrix_csv_path = data_path / 'feature_matrix.csv'
print('Saving feature matrix to', full_matrix_csv_path)
full_matrix.to_csv(full_matrix_csv_path)
full_matrix_pickle_path = replace_extension(full_matrix_csv_path, 'pickle')
print('Saving feature matrix to', full_matrix_pickle_path)
full_matrix.to_csv(full_matrix_pickle_path)
data_desc_filepath = data_path / 'data_desc_normalized.csv'
print('Saving normalized data description to', data_desc_filepath)
full_matrix.describe().T.to_csv(data_desc_filepath)
nodes = sorted(node_set)
node_count = len(nodes)
with pd.HDFStore(find_newest_data_path('parse_tcga_mutations') / 'mutations.hdf5', 'r') as store:
mutations = store['muts']
print('Read mutations')
expr = pd.read_pickle(find_newest_data_path('parse_cosmic_diffexpr') / 'brca_expr.pickle')
print('Read log-fold expression with Hugo symbols')
cutoff = 2
print('Binarizing log-fold expression with cutoff {}'.format(cutoff))
diffexpr_hugo = (expr.abs() > cutoff).astype(float)
hugo_entrez_mapping = read_hugo_entrez_mapping()
diffexpr_hugo_in_mapping = sorted_intersection(diffexpr_hugo.columns, hugo_entrez_mapping)
print(f'{len(diffexpr_hugo_in_mapping)} of {diffexpr_hugo.shape[1]} gene IDs in expr data are in mapping')
diffexpr_overlap = diffexpr_hugo.loc[:, diffexpr_hugo_in_mapping]
new_diffexpr_cols = [hugo_entrez_mapping[col] for col in diffexpr_overlap.columns]
duplicate_col_count = len(new_diffexpr_cols) - len(set(new_diffexpr_cols))
print('Duplicate columns:', duplicate_col_count)
used_entrez_ids = set()
non_dup_col_indices = []
for i, entrez_id in enumerate(new_diffexpr_cols):
if entrez_id not in used_entrez_ids:
non_dup_col_indices.append(i)
used_entrez_ids.add(entrez_id)
diffexpr_overlap.columns = new_diffexpr_cols
diffexpr_overlap_non_dups = diffexpr_overlap.iloc[:, non_dup_col_indices]
diffexpr = diffexpr_overlap_non_dups.loc[:, sorted(diffexpr_overlap_non_dups.columns)]
def propagate_mutations(param_tuple):
i, sample, label, sample_count, vec = param_tuple
if not i % 100:
print('{}: done with {} samples ({:.2f}%)'.format(label, i, (i * 100) / sample_count))
vector = np.matrix(vec).reshape((node_count, 1))
propagated = propagate(w_prime, vector, alpha=args.alpha, verbose=False)
return sample, propagated
data = mutations
label = 'mutations'
sample_count = len(data.index)
data_gene_set = set(data.columns)
common_genes = sorted_intersection(data.columns, node_set)
common_genes_path = data_path / '{}_common_genes.txt'.format(label)
print('{}: saving {} common genes to {}'.format(label, len(common_genes), common_genes_path))
with common_genes_path.open('w') as f:
for gene in common_genes:
print(gene, file=f)
only_mut_genes = sorted(data_gene_set - node_set)
only_mut_genes_path = data_path / '{}_only_mut_genes.txt'.format(label)
print('{}: saving {} data-only genes to {}'.format(label, len(only_mut_genes), only_mut_genes_path))
with only_mut_genes_path.open('w') as f:
for gene in only_mut_genes:
print(gene, file=f)
only_network_genes = sorted(node_set - data_gene_set)
only_network_genes_path = data_path / '{}_only_network_genes.txt'.format(label)
patient_gene_set_muts = pd.DataFrame(0, index=muts.index, columns=range(len(entrez_gene_sets)))
for i, gene_set in enumerate(entrez_gene_sets):
patient_gene_set_muts.loc[:, i] = muts.loc[:, gene_set].any(axis=1).astype(int)
pathway_mut_counts = patient_gene_set_muts.sum(axis=1)
gene_set_mut_matrix_path = data_path / 'gene_set_mut_matrix.pickle'
print('Saving gene set mutation matrix to', gene_set_mut_matrix_path)
patient_gene_set_muts.to_pickle(gene_set_mut_matrix_path)
pathway_mut_count_path = data_path / 'pathway_mut_counts.pickle'
print('Saving pathway mutation counts to', pathway_mut_count_path)
pathway_mut_counts.to_pickle(pathway_mut_count_path)
drugs = ['ai_all', 'arimidex']
feature_label_path = find_newest_data_path(f'compute_drug_features_labels_alpha_{args.alpha:.2f}')
for drug in drugs:
labels_all = pd.read_pickle(feature_label_path / f'labels_{drug}.pickle')
selected_samples = sorted_intersection(labels_all.index, pathway_mut_counts.index)
selected_labels = labels_all.loc[selected_samples]
selected_counts = pathway_mut_counts.loc[selected_samples]
rd = RocData.calculate(selected_labels, selected_counts)
rd.save(data_path / f'roc_data_{drug}.pickle')
plot_roc(rd, f'WExT Pathway Mutation Count ROC: {drug.title()}', output_path / f'{drug}_roc.pdf')
lincs_expr = pd.read_csv(
find_newest_data_path('gct_drug_subset') / 'subset.csv',
header=None,
index_col=0,
)
lincs_expr.columns = drugs
lincs_genes = set(lincs_expr.index)
tcga_genes = set(tcga_expr.columns)
lincs_benchmark_gene_data = pd.read_excel(DATA_PATH /
'Landmark_Genes_n978.xlsx')
lincs_benchmark_genes = set(lincs_benchmark_gene_data.loc[:, 'Gene Symbol'])
common_genes = sorted_intersection(lincs_genes, tcga_genes,
lincs_benchmark_genes)
tcga_only_genes = tcga_genes - lincs_genes
lincs_only_genes = lincs_benchmark_genes - tcga_genes
print('Intersection of TCGA and LINCS gene symbols: {} genes'.format(
len(common_genes)))
print('Gene symbols only in TCGA expression data: {}'.format(
len(tcga_only_genes)))
print('Gene symbols only in LINCS expression data: {}'.format(
len(lincs_only_genes)))
lincs_expr_common_with_dups = lincs_expr.loc[common_genes, :].fillna(0)
lincs_expr_common = pd.DataFrame(0.0, index=common_genes, columns=drugs)
for i, rows in lincs_expr_common_with_dups.groupby(
lincs_expr_common_with_dups.index):
lincs_expr_common.loc[i, :] = rows.mean()