#!/usr/bin/env python3"""Reactome Database Query Helper Script This script provides convenient command-line access to common Reactome operations. Usage:    python reactome_query.py version    python reactome_query.py query <pathway_id>    python reactome_query.py analyze <gene_list_file>    python reactome_query.py search <term>    python reactome_query.py entities <pathway_id> Examples:    python reactome_query.py version    python reactome_query.py query R-HSA-69278    python reactome_query.py analyze genes.txt    python reactome_query.py search "cell cycle"    python reactome_query.py entities R-HSA-69278""" import sysimport jsonimport requestsfrom typing import List, Dict, Optional  class ReactomeClient:    """Client for interacting with Reactome REST APIs"""     CONTENT_BASE = "https://reactome.org/ContentService"    ANALYSIS_BASE = "https://reactome.org/AnalysisService"     def get_version(self) -> str:        """Get Reactome database version"""        response = requests.get(f"{self.CONTENT_BASE}/data/database/version")        response.raise_for_status()        return response.text.strip()     def query_pathway(self, pathway_id: str) -> Dict:        """Query pathway information by ID"""        response = requests.get(f"{self.CONTENT_BASE}/data/query/{pathway_id}")        response.raise_for_status()        return response.json()     def get_pathway_entities(self, pathway_id: str) -> List[Dict]:        """Get participating entities in a pathway"""        response = requests.get(            f"{self.CONTENT_BASE}/data/event/{pathway_id}/participatingPhysicalEntities"        )        response.raise_for_status()        return response.json()     def search_pathways(self, term: str) -> List[Dict]:        """Search for pathways by name"""        response = requests.get(            f"{self.CONTENT_BASE}/data/query",            params={"name": term}        )        response.raise_for_status()        return response.json()     def analyze_genes(self, gene_list: List[str]) -> Dict:        """Perform pathway enrichment analysis on gene list"""        data = "\n".join(gene_list)        response = requests.post(            f"{self.ANALYSIS_BASE}/identifiers/",            headers={"Content-Type": "text/plain"},            data=data        )        response.raise_for_status()        return response.json()     def get_analysis_by_token(self, token: str) -> Dict:        """Retrieve analysis results by token"""        response = requests.get(f"{self.ANALYSIS_BASE}/token/{token}")        response.raise_for_status()        return response.json()  def print_json(data):    """Pretty print JSON data"""    print(json.dumps(data, indent=2))  def command_version():    """Get and display Reactome version"""    client = ReactomeClient()    version = client.get_version()    print(f"Reactome Database Version: {version}")  def command_query(pathway_id: str):    """Query and display pathway information"""    client = ReactomeClient()    try:        pathway = client.query_pathway(pathway_id)        print(f"Pathway: {pathway['displayName']}")        print(f"ID: {pathway['stId']}")        print(f"Type: {pathway['schemaClass']}")         if 'species' in pathway and pathway['species']:            species = pathway['species'][0]['displayName']            print(f"Species: {species}")         if 'summation' in pathway and pathway['summation']:            summation = pathway['summation'][0]['text']            print(f"\nDescription: {summation}")         print("\nFull JSON response:")        print_json(pathway)     except requests.HTTPError as e:        if e.response.status_code == 404:            print(f"Error: Pathway '{pathway_id}' not found")        else:            print(f"Error: {e}")        sys.exit(1)  def command_entities(pathway_id: str):    """Display entities participating in a pathway"""    client = ReactomeClient()    try:        entities = client.get_pathway_entities(pathway_id)        print(f"Entities in pathway {pathway_id}: {len(entities)} total\n")         # Group by type        by_type = {}        for entity in entities:            entity_type = entity['schemaClass']            if entity_type not in by_type:                by_type[entity_type] = []            by_type[entity_type].append(entity)         # Display by type        for entity_type, entities_list in sorted(by_type.items()):            print(f"{entity_type} ({len(entities_list)}):")            for entity in entities_list[:10]:  # Show first 10                print(f"  - {entity['stId']}: {entity['displayName']}")            if len(entities_list) > 10:                print(f"  ... and {len(entities_list) - 10} more")            print()     except requests.HTTPError as e:        if e.response.status_code == 404:            print(f"Error: Pathway '{pathway_id}' not found")        else:            print(f"Error: {e}")        sys.exit(1)  def command_search(term: str):    """Search for pathways by term"""    client = ReactomeClient()    try:        results = client.search_pathways(term)        print(f"Search results for '{term}': {len(results)} found\n")         for result in results[:20]:  # Show first 20            print(f"{result['stId']}: {result['displayName']}")            if 'species' in result and result['species']:                species = result['species'][0]['displayName']                print(f"  Species: {species}")            print(f"  Type: {result['schemaClass']}")            print()         if len(results) > 20:            print(f"... and {len(results) - 20} more results")     except requests.HTTPError as e:        print(f"Error: {e}")        sys.exit(1)  def command_analyze(gene_file: str):    """Perform pathway enrichment analysis"""    client = ReactomeClient()     # Read gene list    try:        with open(gene_file, 'r') as f:            genes = [line.strip() for line in f if line.strip()]    except FileNotFoundError:        print(f"Error: File '{gene_file}' not found")        sys.exit(1)     print(f"Analyzing {len(genes)} genes...")     try:        result = client.analyze_genes(genes)         # Display summary        summary = result['summary']        print(f"\nAnalysis Type: {summary['type']}")        print(f"Token: {summary['token']} (valid for 7 days)")        print(f"Species: {summary.get('species', 'N/A')}")         # Display pathways        pathways = result.get('pathways', [])        print(f"\nEnriched Pathways: {len(pathways)} found")         # Show significant pathways (FDR < 0.05)        significant = [p for p in pathways if p['entities']['fdr'] < 0.05]        print(f"Significant (FDR < 0.05): {len(significant)}\n")         # Display top 10 pathways        print("Top 10 Pathways:")        for i, pathway in enumerate(pathways[:10], 1):            print(f"\n{i}. {pathway['name']}")            print(f"   ID: {pathway['stId']}")            entities = pathway['entities']            print(f"   Found: {entities['found']}/{entities['total']} entities")            print(f"   p-value: {entities['pValue']:.6e}")            print(f"   FDR: {entities['fdr']:.6e}")         # Generate browser URL for top pathway        if pathways:            token = summary['token']            top_pathway = pathways[0]['stId']            url = f"https://reactome.org/PathwayBrowser/#{top_pathway}&DTAB=AN&ANALYSIS={token}"            print(f"\nView top result in browser:")            print(url)         # Save full results        output_file = gene_file.replace('.txt', '_results.json')        with open(output_file, 'w') as f:            json.dump(result, f, indent=2)        print(f"\nFull results saved to: {output_file}")     except requests.HTTPError as e:        print(f"Error: {e}")        sys.exit(1)  def print_usage():    """Print usage information"""    print(__doc__)  def main():    if len(sys.argv) < 2:        print_usage()        sys.exit(1)     command = sys.argv[1].lower()     if command == "version":        command_version()     elif command == "query":        if len(sys.argv) < 3:            print("Error: pathway_id required")            print("Usage: python reactome_query.py query <pathway_id>")            sys.exit(1)        command_query(sys.argv[2])     elif command == "entities":        if len(sys.argv) < 3:            print("Error: pathway_id required")            print("Usage: python reactome_query.py entities <pathway_id>")            sys.exit(1)        command_entities(sys.argv[2])     elif command == "search":        if len(sys.argv) < 3:            print("Error: search term required")            print("Usage: python reactome_query.py search <term>")            sys.exit(1)        command_search(" ".join(sys.argv[2:]))     elif command == "analyze":        if len(sys.argv) < 3:            print("Error: gene list file required")            print("Usage: python reactome_query.py analyze <gene_list_file>")            sys.exit(1)        command_analyze(sys.argv[2])     else:        print(f"Error: Unknown command '{command}'")        print_usage()        sys.exit(1)  if __name__ == "__main__":    main()