#!/usr/bin/env python3"""PubChem Bioactivity Data Retrieval This script provides functions for retrieving biological activity datafrom PubChem for compounds and assays.""" import sysimport jsonimport timefrom typing import Dict, List, Optional try:    import requestsexcept ImportError:    print("Error: requests is not installed. Install it with: pip install requests")    sys.exit(1)  BASE_URL = "https://pubchem.ncbi.nlm.nih.gov/rest/pug"PUG_VIEW_URL = "https://pubchem.ncbi.nlm.nih.gov/rest/pug_view" # Rate limiting: 5 requests per second maximumREQUEST_DELAY = 0.21  # seconds between requests  def rate_limited_request(url: str, method: str = 'GET', **kwargs) -> Optional[requests.Response]:    """    Make a rate-limited request to PubChem API.     Args:        url: Request URL        method: HTTP method ('GET' or 'POST')        **kwargs: Additional arguments for requests     Returns:        Response object or None on error    """    time.sleep(REQUEST_DELAY)     try:        if method.upper() == 'GET':            response = requests.get(url, **kwargs)        else:            response = requests.post(url, **kwargs)         response.raise_for_status()        return response    except requests.exceptions.RequestException as e:        print(f"Request error: {e}")        return None  def get_bioassay_summary(cid: int) -> Optional[Dict]:    """    Get bioassay summary for a compound.     Args:        cid: PubChem Compound ID     Returns:        Dictionary containing bioassay summary data    """    url = f"{BASE_URL}/compound/cid/{cid}/assaysummary/JSON"    response = rate_limited_request(url)     if response and response.status_code == 200:        return response.json()    return None  def get_compound_bioactivities(    cid: int,    activity_outcome: Optional[str] = None) -> List[Dict]:    """    Get bioactivity data for a compound.     Args:        cid: PubChem Compound ID        activity_outcome: Filter by activity ('active', 'inactive', 'inconclusive')     Returns:        List of bioactivity records    """    data = get_bioassay_summary(cid)     if not data:        return []     activities = []    table = data.get('Table', {})     for row in table.get('Row', []):        activity = {}        for i, cell in enumerate(row.get('Cell', [])):            column_name = table['Columns']['Column'][i]            activity[column_name] = cell         if activity_outcome:            if activity.get('Activity Outcome', '').lower() == activity_outcome.lower():                activities.append(activity)        else:            activities.append(activity)     return activities  def get_assay_description(aid: int) -> Optional[Dict]:    """    Get detailed description for a specific assay.     Args:        aid: PubChem Assay ID (AID)     Returns:        Dictionary containing assay description    """    url = f"{BASE_URL}/assay/aid/{aid}/description/JSON"    response = rate_limited_request(url)     if response and response.status_code == 200:        return response.json()    return None  def get_assay_targets(aid: int) -> List[str]:    """    Get biological targets for an assay.     Args:        aid: PubChem Assay ID     Returns:        List of target names    """    description = get_assay_description(aid)     if not description:        return []     targets = []    assay_data = description.get('PC_AssayContainer', [{}])[0]    assay = assay_data.get('assay', {})     # Extract target information    descr = assay.get('descr', {})    for target in descr.get('target', []):        mol_id = target.get('mol_id', '')        name = target.get('name', '')        if name:            targets.append(name)        elif mol_id:            targets.append(f"GI:{mol_id}")     return targets  def search_assays_by_target(    target_name: str,    max_results: int = 100) -> List[int]:    """    Search for assays targeting a specific protein or gene.     Args:        target_name: Name of the target (e.g., 'EGFR', 'p53')        max_results: Maximum number of results     Returns:        List of Assay IDs (AIDs)    """    # Use PubChem's text search for assays    url = f"{BASE_URL}/assay/target/{target_name}/aids/JSON"    response = rate_limited_request(url)     if response and response.status_code == 200:        data = response.json()        aids = data.get('IdentifierList', {}).get('AID', [])        return aids[:max_results]    return []  def get_active_compounds_in_assay(aid: int, max_results: int = 1000) -> List[int]:    """    Get list of active compounds in an assay.     Args:        aid: PubChem Assay ID        max_results: Maximum number of results     Returns:        List of Compound IDs (CIDs) that showed activity    """    url = f"{BASE_URL}/assay/aid/{aid}/cids/JSON?cids_type=active"    response = rate_limited_request(url)     if response and response.status_code == 200:        data = response.json()        cids = data.get('IdentifierList', {}).get('CID', [])        return cids[:max_results]    return []  def get_compound_annotations(cid: int, section: Optional[str] = None) -> Optional[Dict]:    """    Get comprehensive compound annotations from PUG-View.     Args:        cid: PubChem Compound ID        section: Specific section to retrieve (e.g., 'Pharmacology and Biochemistry')     Returns:        Dictionary containing annotation data    """    url = f"{PUG_VIEW_URL}/data/compound/{cid}/JSON"     if section:        url += f"?heading={section}"     response = rate_limited_request(url)     if response and response.status_code == 200:        return response.json()    return None  def get_drug_information(cid: int) -> Optional[Dict]:    """    Get drug and medication information for a compound.     Args:        cid: PubChem Compound ID     Returns:        Dictionary containing drug information    """    return get_compound_annotations(cid, section="Drug and Medication Information")  def get_safety_hazards(cid: int) -> Optional[Dict]:    """    Get safety and hazard information for a compound.     Args:        cid: PubChem Compound ID     Returns:        Dictionary containing safety information    """    return get_compound_annotations(cid, section="Safety and Hazards")  def summarize_bioactivities(cid: int) -> Dict:    """    Generate a summary of bioactivity data for a compound.     Args:        cid: PubChem Compound ID     Returns:        Dictionary with bioactivity summary statistics    """    activities = get_compound_bioactivities(cid)     summary = {        'total_assays': len(activities),        'active': 0,        'inactive': 0,        'inconclusive': 0,        'unspecified': 0,        'assay_types': {}    }     for activity in activities:        outcome = activity.get('Activity Outcome', '').lower()         if 'active' in outcome:            summary['active'] += 1        elif 'inactive' in outcome:            summary['inactive'] += 1        elif 'inconclusive' in outcome:            summary['inconclusive'] += 1        else:            summary['unspecified'] += 1     return summary  def find_compounds_by_bioactivity(    target: str,    threshold: Optional[float] = None,    max_compounds: int = 100) -> List[Dict]:    """    Find compounds with bioactivity against a specific target.     Args:        target: Target name (e.g., 'EGFR')        threshold: Activity threshold (if applicable)        max_compounds: Maximum number of compounds to return     Returns:        List of dictionaries with compound information and activity data    """    # Step 1: Find assays for the target    assay_ids = search_assays_by_target(target, max_results=10)     if not assay_ids:        print(f"No assays found for target: {target}")        return []     # Step 2: Get active compounds from these assays    compound_set = set()    compound_data = []     for aid in assay_ids[:5]:  # Limit to first 5 assays        active_cids = get_active_compounds_in_assay(aid, max_results=max_compounds)         for cid in active_cids:            if cid not in compound_set and len(compound_data) < max_compounds:                compound_set.add(cid)                compound_data.append({                    'cid': cid,                    'aid': aid,                    'target': target                })         if len(compound_data) >= max_compounds:            break     return compound_data  def main():    """Example usage of bioactivity query functions."""     # Example 1: Get bioassay summary for aspirin (CID 2244)    print("Example 1: Getting bioassay summary for aspirin (CID 2244)...")    summary = summarize_bioactivities(2244)    print(json.dumps(summary, indent=2))     # Example 2: Get active bioactivities for a compound    print("\nExample 2: Getting active bioactivities for aspirin...")    activities = get_compound_bioactivities(2244, activity_outcome='active')    print(f"Found {len(activities)} active bioactivities")    if activities:        print(f"First activity: {activities[0].get('Assay Name', 'N/A')}")     # Example 3: Get assay information    print("\nExample 3: Getting assay description...")    if activities:        aid = activities[0].get('AID', 0)        targets = get_assay_targets(aid)        print(f"Assay {aid} targets: {', '.join(targets) if targets else 'N/A'}")     # Example 4: Search for compounds targeting EGFR    print("\nExample 4: Searching for EGFR inhibitors...")    egfr_compounds = find_compounds_by_bioactivity('EGFR', max_compounds=5)    print(f"Found {len(egfr_compounds)} compounds with EGFR activity")    for comp in egfr_compounds[:5]:        print(f"  CID {comp['cid']} (from AID {comp['aid']})")  if __name__ == '__main__':    main()