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# Path Configuration
from tools.preprocess import *

# Processing context
trait = "Head_and_Neck_Cancer"
cohort = "GSE218109"

# Input paths
in_trait_dir = "../DATA/GEO/Head_and_Neck_Cancer"
in_cohort_dir = "../DATA/GEO/Head_and_Neck_Cancer/GSE218109"

# Output paths
out_data_file = "./output/preprocess/3/Head_and_Neck_Cancer/GSE218109.csv"
out_gene_data_file = "./output/preprocess/3/Head_and_Neck_Cancer/gene_data/GSE218109.csv"
out_clinical_data_file = "./output/preprocess/3/Head_and_Neck_Cancer/clinical_data/GSE218109.csv"
json_path = "./output/preprocess/3/Head_and_Neck_Cancer/cohort_info.json"

# Get relevant file paths
soft_file_path, matrix_file_path = geo_get_relevant_filepaths(in_cohort_dir)

# Extract background info and clinical data from the matrix file
background_info, clinical_data = get_background_and_clinical_data(matrix_file_path)

# Get dictionary of unique values per row in clinical data
unique_values_dict = get_unique_values_by_row(clinical_data)

# Print background info
print("Background Information:")
print("-" * 50)
print(background_info)
print("\n")

# Print clinical data unique values
print("Sample Characteristics:")
print("-" * 50)
for row, values in unique_values_dict.items():
    print(f"{row}:")
    print(f"  {values}")
    print()
# Gene expression data availability check
# This dataset is about transcriptional profiling of ESCC tumors, 
# indicating it contains gene expression data
is_gene_available = True

# Define trait row and converter function
# p53 status (row 5) can be converted to binary with NS+ as 1 and NS- as 0
trait_row = 5
def convert_trait(value):
    if not value or 'NA' in value:
        return None
    value = value.split(': ')[1]
    if 'NS+' in value:
        return 1
    elif 'NS-' in value:
        return 0
    return None

# Define age row and converter function 
age_row = 1
def convert_age(value):
    if not value or 'NA' in value:
        return None
    try:
        return float(value.split(': ')[1])
    except:
        return None

# Define gender row and converter function
gender_row = 0
def convert_gender(value):
    if not value or 'NA' in value:
        return None
    value = value.split(': ')[1]
    if value.upper() == 'F':
        return 0
    elif value.upper() == 'M':
        return 1
    return None

# Validate dataset availability
validate_and_save_cohort_info(is_final=False, 
                            cohort=cohort,
                            info_path=json_path,
                            is_gene_available=is_gene_available,
                            is_trait_available=(trait_row is not None))

# Extract clinical features
clinical_features = geo_select_clinical_features(clinical_data, 
                                               trait=trait,
                                               trait_row=trait_row,
                                               convert_trait=convert_trait,
                                               age_row=age_row,
                                               convert_age=convert_age, 
                                               gender_row=gender_row,
                                               convert_gender=convert_gender)

# Preview and save clinical data
preview_df(clinical_features)
clinical_features.to_csv(out_clinical_data_file)
# Extract gene expression data
genetic_data = get_genetic_data(matrix_file_path)

# Print first 20 probe IDs
print("First 20 probe IDs:")
print(genetic_data.index[:20])
# The identifiers appear to be numeric probe IDs rather than human gene symbols
# These need to be mapped to gene symbols for proper biological interpretation
requires_gene_mapping = True
# Extract gene annotation from SOFT file
gene_annotation = get_gene_annotation(soft_file_path)

# Filter out control probes
gene_annotation = gene_annotation[gene_annotation['CONTROL_TYPE'] != 'pos']

# Preview column names and first 20 values
preview_dict = preview_df(gene_annotation, n=20)
print("Column names and preview values:")
for col, values in preview_dict.items():
    print(f"\n{col}:")
    print(values)
# Extract gene mapping from annotation
# 'ID' column in gene_annotation matches probe IDs in genetic_data
# 'GENE_SYMBOL' column contains human gene symbols
mapping_data = get_gene_mapping(gene_annotation, prob_col='ID', gene_col='GENE_SYMBOL')

# Convert probe-level measurements to gene expression data
gene_data = apply_gene_mapping(genetic_data, mapping_data)

# Preview first few rows of gene data
print("\nFirst few rows of gene expression data:")
print(gene_data.head())
# 1. Normalize gene symbols and save normalized gene data
normalized_gene_data = normalize_gene_symbols_in_index(gene_data)
os.makedirs(os.path.dirname(out_gene_data_file), exist_ok=True)
normalized_gene_data.to_csv(out_gene_data_file)

# Read the processed clinical data file 
clinical_df = pd.read_csv(out_clinical_data_file, index_col=0)

# Link clinical and genetic data using the normalized gene data
linked_data = geo_link_clinical_genetic_data(clinical_df, normalized_gene_data)

# Handle missing values systematically
linked_data = handle_missing_values(linked_data, trait)

# Detect bias in trait and demographic features, remove biased demographic features
is_biased, linked_data = judge_and_remove_biased_features(linked_data, trait)

# Validate data quality and save cohort info
note = "Gene expression data from glucocorticoid sensitivity study."
is_usable = validate_and_save_cohort_info(
    is_final=True,
    cohort=cohort,
    info_path=json_path,
    is_gene_available=True,
    is_trait_available=True,
    is_biased=is_biased,
    df=linked_data,
    note=note
)

# Save linked data if usable
if is_usable:
    os.makedirs(os.path.dirname(out_data_file), exist_ok=True)
    linked_data.to_csv(out_data_file)
else:
    print(f"Dataset {cohort} did not pass quality validation and will not be saved.")