import functools import json import logging import os import re import socket import sys import time import traceback from datetime import datetime from ftplib import FTP from typing import Optional, List, Tuple from urllib.parse import urlparse import numpy as np import pandas as pd from Bio import Entrez from dotenv import load_dotenv from tqdm import tqdm # Load environment variables load_dotenv() # Configure logging log_dir = "logs" os.makedirs(log_dir, exist_ok=True) log_file = os.path.join(log_dir, f"geo_download_{datetime.now().strftime('%Y%m%d_%H%M%S')}.log") logging.basicConfig( level=logging.INFO, format='%(asctime)s - %(levelname)s - %(message)s', handlers=[ logging.FileHandler(log_file), logging.StreamHandler(sys.stdout) ] ) logger = logging.getLogger(__name__) class FTPConfig: CONNECT_TIMEOUT = 600 # 120 for max 100 datasets # Initial connection timeout DATA_TIMEOUT = 600 # Data transfer timeout MAX_RETRIES = 2 INITIAL_DELAY = 1 MAX_DELAY = 4 BLOCK_SIZE = 32768 SIZE_LIMIT_MB = 100 def checkpoint_read(path: str, show: bool = True) -> Tuple[int, int]: if not os.path.exists(path): if show: logger.info("No checkpoint found, starting from beginning") with open(path, 'w') as f: f.write("0;0") return 0, 0 try: with open(path, 'r') as f: checkpoint = f.read() last_checkpoint_i, last_checkpoint_j = map(int, checkpoint.strip().split(";")) if show: logger.info(f"Resuming from checkpoint: i={last_checkpoint_i}, j={last_checkpoint_j}") return last_checkpoint_i, last_checkpoint_j except Exception as e: logger.error(f"Error reading checkpoint, starting from beginning: {str(e)}\n{traceback.format_exc()}") return 0, 0 def clean_filename(filename: str) -> str: pattern = r'[\\/:\*\?"<>\|\r\n\t]+' # Matches \ / : * ? " < > | \r \n \t filename = re.sub(pattern, '-', filename) filename = '_'.join(filename.split()) filename = ''.join(filename.split("'")) return filename # FTP linking information def retry_on_ftp_error(func): @functools.wraps(func) def wrapper(*args, **kwargs): max_attempts = FTPConfig.MAX_RETRIES attempt = 0 while attempt < max_attempts: try: return func(*args, **kwargs) except (socket.timeout, EOFError, ConnectionError) as e: attempt += 1 if attempt == max_attempts: raise logger.error(f"Connection error: {str(e)}. Retrying... ({attempt}/{max_attempts})") time.sleep(1) # Fixed 1-second delay for simplicity return None return wrapper @retry_on_ftp_error def ftp_connect(host, timeout=FTPConfig.CONNECT_TIMEOUT): # Reduced initial connection timeout """Establish FTP connection""" ftp = FTP(host, timeout=timeout) ftp.login() ftp.set_pasv(True) # Added passive mode for better compatibility return ftp @retry_on_ftp_error def download_files(ftp, remote_file_paths, local_file_paths): """Download files""" for remote_file_path, local_file_path in zip(remote_file_paths, local_file_paths): try: with open(local_file_path, 'wb') as file: ftp.retrbinary('RETR ' + remote_file_path, file.write, blocksize=FTPConfig.BLOCK_SIZE) logger.info(f"Successfully downloaded: {os.path.basename(local_file_path)}") except Exception as e: logger.error(f"Failed to download {remote_file_path}: {str(e)}\n{traceback.format_exc()}") if os.path.exists(local_file_path): os.remove(local_file_path) raise def get_GEO_series_access(search_term: str, batch_size: int = 100, max_results: Optional[int] = None) -> Tuple[List[str], List[str], List[int]]: """Search and retrieve GEO datasets for a given trait. Filters for human studies (2010-2025) with 30-10000 samples. Includes expression profiling and genome variation datasets. Returns: Tuple of (dataset_accessions, ftp_links, sample_sizes) """ try: Entrez.email = os.getenv("ENTREZ_EMAIL") Entrez.api_key = os.getenv("ENTREZ_API_KEY") handle = None DATASET_TYPES = [ "expression profiling by array", "expression profiling by high throughput sequencing", "genome variation profiling by high throughput sequencing", "genome variation profiling by snp array", "snp genotyping by snp array", "third party reanalysis" ] dataset_filter = "(" + " OR ".join( [f"\"{dataset_type}\"[DataSet Type]" for dataset_type in DATASET_TYPES]) + ")" query = ( f"(30:10000[Number of Samples])" f" AND (\"Homo sapiens\"[Organism])" f" AND (2010:2025[Publication Date])" f" AND ({search_term})" f" AND {dataset_filter}" ) logger.info(f"Search query: {query}") try: # First pass: retmax=0 to only get the count of matching records handle = Entrez.esearch(db="gds", term=query, retmax=0, timeout=30) record_first_pass = Entrez.read(handle) handle.close() total_count = int(record_first_pass["Count"]) logger.info(f"Total results for query: {total_count}") # If user wants to cap results if max_results is not None and total_count > max_results: total_count = max_results logger.info(f"Limiting results to user-specified maximum: {max_results}") all_ids = [] retstart = 0 total_batches = (total_count - 1) // batch_size + 1 # Iteratively fetch IDs in batches while retstart < total_count: try: current_batch_size = min(batch_size, total_count - retstart) current_batch = retstart // batch_size + 1 logger.info(f"Fetching batch {current_batch} of {total_batches} (size: {current_batch_size})") handle = Entrez.esearch( db="gds", term=query, retmax=current_batch_size, retstart=retstart, timeout=30 ) record = Entrez.read(handle) handle.close() if "IdList" in record: batch_ids = record["IdList"] all_ids.extend(batch_ids) logger.info(f"Successfully retrieved {len(batch_ids)} IDs in batch {current_batch}") else: logger.warning(f"No IdList found in record batch at retstart={retstart}") retstart += current_batch_size # Add rate limiting between batches if retstart < total_count: time.sleep(0.5) # 500ms delay between batches except Exception as e: logger.error(f"Error in batch {current_batch}: {str(e)}\n{traceback.format_exc()}") break logger.info(f"Found {len(all_ids)} datasets for: {search_term}") except Exception as e: logger.error(f"Error searching GEO database: {str(e)}\n{traceback.format_exc()}") return [], [], [] finally: if handle: handle.close() dataset_accessions = [] Series_FTP_Links = [] sample_sizes = [] for dataset_id in all_ids: try: dataset_handle = Entrez.esummary(db="gds", id=dataset_id) dataset_summary = Entrez.read(dataset_handle) if not dataset_summary: logger.warning(f"Empty summary for dataset {dataset_id}") continue sample_size = int(dataset_summary[0]['n_samples']) dataset_accession = dataset_summary[0]['Accession'] ftp_link = dataset_summary[0].get('FTPLink', '') if not ftp_link: logger.warning(f"No FTP link for dataset {dataset_id}") continue dataset_accessions.append(dataset_accession) Series_FTP_Links.append(ftp_link) sample_sizes.append(sample_size) except Exception as e: logger.error(f"Error processing dataset {dataset_id}: {str(e)}\n{traceback.format_exc()}") continue finally: dataset_handle.close() logger.info(f"Successfully processed {len(dataset_accessions)} datasets for: {search_term}") return dataset_accessions, Series_FTP_Links, sample_sizes except Exception as e: logger.error(f"Unexpected error in GEO access: {str(e)}\n{traceback.format_exc()}") return [], [], [] def download_trait_data(dataset_inf, key_word, base_dir, checkpoint_path, max_download_per_trait=10): """Download GEO datasets for a given trait. For each dataset, downloads: - Matrix files (expression/variation data) - Family files (metadata) Limited to max_download_per_trait datasets, with size checks. """ ftp_host = 'ftp.ncbi.nlm.nih.gov' ftp = None downloaded_sample_sizes = [] # Track sample sizes of downloaded datasets try: ftp = ftp_connect(ftp_host) dataset_accessions, Series_FTP_Links, sample_sizes = dataset_inf local_dir = os.path.join(base_dir, clean_filename(key_word)) if not os.path.exists(local_dir): os.makedirs(local_dir) Series_num = len(Series_FTP_Links) _, checkpoint_j = checkpoint_read(checkpoint_path) for j, Series_FTP_Link in enumerate(Series_FTP_Links): if j < checkpoint_j: continue try: parsed_url = urlparse(Series_FTP_Link) ftp_path = parsed_url.path try: ftp.cwd(ftp_path) except: try: ftp.quit() except: pass ftp = ftp_connect(ftp_host) ftp.cwd(ftp_path) file_list = ftp.nlst() logger.debug(f"File list: {file_list}") matrix_flag = False family_flag = False for file_name in file_list: if "matrix" in file_name: matrix_flag = True if "soft" in file_name: family_flag = True if not matrix_flag or not family_flag: logger.debug(f"Skipping series {j}: missing matrix or family files") continue # Process matrix files ftp.cwd(f'{ftp_path}matrix/') matrix_file_list = ftp.nlst() logger.debug(f"Matrix files: {matrix_file_list}") matrix_file_urls = [] matrix_file_names = [] for filename1 in matrix_file_list: if 'matrix' in filename1 and 'xml' not in filename1: ftp.sendcmd("TYPE I") matrix_file_size = ftp.size(filename1) / (1024 * 1024) if matrix_file_size > 0.1 and matrix_file_size < FTPConfig.SIZE_LIMIT_MB: logger.info(f"Matrix file {filename1} is available with size {matrix_file_size:.2f} MB") matrix_file_url = f'{ftp_path}matrix/{filename1}' matrix_file_urls.append(matrix_file_url) matrix_file_names.append(filename1) # Process family files ftp.cwd(f'{ftp_path}soft/') family_file_list = ftp.nlst() logger.debug(f"Family files: {family_file_list}") family_file_urls = [] family_file_names = [] for filename2 in family_file_list: if 'family' in filename2 and 'xml' not in filename2: ftp.sendcmd("TYPE I") family_file_size = ftp.size(filename2) / (1024 * 1024) if family_file_size < FTPConfig.SIZE_LIMIT_MB: logger.info(f"Family file {filename2} is available with size {family_file_size:.2f} MB") family_file_url = f'{ftp_path}soft/{filename2}' family_file_urls.append(family_file_url) family_file_names.append(filename2) if len(family_file_urls) > 0 and len(matrix_file_urls) > 0: local_dir_series = os.path.join(local_dir, dataset_accessions[j]) if not os.path.exists(local_dir_series): os.makedirs(local_dir_series) local_matrix_filenames = [os.path.join(local_dir_series, mfn) for mfn in matrix_file_names] download_files(ftp, remote_file_paths=matrix_file_urls, local_file_paths=local_matrix_filenames) local_family_filenames = [os.path.join(local_dir_series, ffn) for ffn in family_file_names] download_files(ftp, remote_file_paths=family_file_urls, local_file_paths=local_family_filenames) logger.info(f"Downloaded: {matrix_file_names} and {family_file_names} for trait {key_word}") downloaded_sample_sizes.append(sample_sizes[j]) if len(downloaded_sample_sizes) >= max_download_per_trait: break # Save the index of the downloaded dataset to checkpoint file checkpoint_i, _ = checkpoint_read(checkpoint_path, show=False) with open(checkpoint_path, 'w') as f: f.write(f"{checkpoint_i};{(j + 1)}") else: logger.info( f"No suitable gene expression data in series {j} ({Series_num} series for trait {key_word} in total)") except Exception as e: logger.error(f"Error processing series {j}: {str(e)}\n{traceback.format_exc()}") continue finally: if ftp: try: ftp.quit() except: pass return downloaded_sample_sizes def read_keywords() -> List[str]: """Read trait keywords from metadata 'task_info'. Returns a list of traits to search in GEO database. """ file_path = "../metadata/task_info.json" try: with open(file_path, "r") as f: task_info = json.load(f) return sorted(list(task_info.keys())) except Exception as e: logger.error(f"Error reading keywords file: {str(e)}\n{traceback.format_exc()}") return [] if __name__ == '__main__': """Search and download GEO datasets for each trait. Reads traits from the metadata, searches GEO database, and downloads relevant datasets with checkpointing. """ key_word = read_keywords() logger.info(f"Found {len(key_word)} keywords to process") logger.info(f"Keywords: {key_word}") checkpoint_path = "./GEO_data_download_Checkpoint.txt" last_checkpoint_i, last_checkpoint_j = checkpoint_read(checkpoint_path) try: sample_sizes = [] total_traits = len(key_word) with tqdm(total=total_traits, desc="Traits Progress") as traits_pbar: if last_checkpoint_i > 0: traits_pbar.update(last_checkpoint_i) for idx, keyword in enumerate(key_word): if idx < last_checkpoint_i: continue logger.info(f"\nProcessing trait ({idx + 1}/{total_traits}): {keyword}") try: data_info = get_GEO_series_access(search_term=keyword, max_results=200) if not data_info[1]: # Series_FTP_Links logger.warning(f"No valid datasets found for trait: {keyword}") traits_pbar.update(1) continue trait_downloaded_sizes = download_trait_data(dataset_inf=data_info, key_word=keyword, base_dir='/media/techt/DATA/GEO_test', checkpoint_path=checkpoint_path, max_download_per_trait=10) sample_sizes.extend(trait_downloaded_sizes) with open(checkpoint_path, 'w') as g: g.write(f"{idx + 1};0") traits_pbar.update(1) except Exception as e: logger.error(f"Error processing keyword {keyword}: {str(e)}\n{traceback.format_exc()}") raise if sample_sizes: logger.info("\nFinal Statistics:") logger.info(f"Mean samples: {np.mean(sample_sizes):.2f}") logger.info(f"Std dev: {np.std(sample_sizes):.2f}") logger.info(f"Total datasets: {len(sample_sizes)}") else: logger.warning("No sample sizes were collected during execution.") except Exception as e: logger.error(f"Unexpected error in main: {str(e)}\n{traceback.format_exc()}")