Update app.py

app.py

@@ -1,155 +1,246 @@
-runtime error
-Exit code: 1. Reason: cio.run(self.serve(sockets=sockets))
-           ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^
-  File "/usr/local/lib/python3.11/asyncio/runners.py", line 190, in run
-    return runner.run(main)
-           ^^^^^^^^^^^^^^^^
-  File "/usr/local/lib/python3.11/asyncio/runners.py", line 118, in run
-    return self._loop.run_until_complete(task)
-           ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^
-  File "/usr/local/lib/python3.11/asyncio/base_events.py", line 654, in run_until_complete
-    return future.result()
-           ^^^^^^^^^^^^^^^
-  File "/usr/local/lib/python3.11/site-packages/uvicorn/server.py", line 71, in serve
-    await self._serve(sockets)
-  File "/usr/local/lib/python3.11/site-packages/uvicorn/server.py", line 78, in _serve
-    config.load()
-  File "/usr/local/lib/python3.11/site-packages/uvicorn/config.py", line 436, in load
-    self.loaded_app = import_from_string(self.app)
-                      ^^^^^^^^^^^^^^^^^^^^^^^^^^^^
-  File "/usr/local/lib/python3.11/site-packages/uvicorn/importer.py", line 19, in import_from_string
-    module = importlib.import_module(module_str)
-             ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^
-  File "/usr/local/lib/python3.11/importlib/__init__.py", line 126, in import_module
-    return _bootstrap._gcd_import(name[level:], package, level)
-           ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^
-  File "<frozen importlib._bootstrap>", line 1204, in _gcd_import
-  File "<frozen importlib._bootstrap>", line 1176, in _find_and_load
-  File "<frozen importlib._bootstrap>", line 1147, in _find_and_load_unlocked
-  File "<frozen importlib._bootstrap>", line 690, in _load_unlocked
-  File "<frozen importlib._bootstrap_external>", line 936, in exec_module
-  File "<frozen importlib._bootstrap_external>", line 1074, in get_code
-  File "<frozen importlib._bootstrap_external>", line 1004, in source_to_code
-  File "<frozen importlib._bootstrap>", line 241, in _call_with_frames_removed
-  File "/app/app.py", line 1
-    <PASTE YOUR WHOLE app.py CONTENT HERE EXACTLY>
-    ^
-SyntaxError: invalid syntax
-Container logs:
-
-===== Application Startup at 2025-09-06 03:54:41 =====
-
-Traceback (most recent call last):
-  File "/usr/local/bin/uvicorn", line 8, in <module>
-    sys.exit(main())
-             ^^^^^^
-  File "/usr/local/lib/python3.11/site-packages/click/core.py", line 1442, in __call__
-    return self.main(*args, **kwargs)
-           ^^^^^^^^^^^^^^^^^^^^^^^^^^
-  File "/usr/local/lib/python3.11/site-packages/click/core.py", line 1363, in main
-    rv = self.invoke(ctx)
-         ^^^^^^^^^^^^^^^^
-  File "/usr/local/lib/python3.11/site-packages/click/core.py", line 1226, in invoke
-    return ctx.invoke(self.callback, **ctx.params)
-           ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^
-  File "/usr/local/lib/python3.11/site-packages/click/core.py", line 794, in invoke
-    return callback(*args, **kwargs)
-           ^^^^^^^^^^^^^^^^^^^^^^^^^
-  File "/usr/local/lib/python3.11/site-packages/uvicorn/main.py", line 413, in main
-    run(
-  File "/usr/local/lib/python3.11/site-packages/uvicorn/main.py", line 580, in run
-    server.run()
-  File "/usr/local/lib/python3.11/site-packages/uvicorn/server.py", line 67, in run
-    return asyncio.run(self.serve(sockets=sockets))
-           ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^
-  File "/usr/local/lib/python3.11/asyncio/runners.py", line 190, in run
-    return runner.run(main)
-           ^^^^^^^^^^^^^^^^
-  File "/usr/local/lib/python3.11/asyncio/runners.py", line 118, in run
-    return self._loop.run_until_complete(task)
-           ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^
-  File "/usr/local/lib/python3.11/asyncio/base_events.py", line 654, in run_until_complete
-    return future.result()
-           ^^^^^^^^^^^^^^^
-  File "/usr/local/lib/python3.11/site-packages/uvicorn/server.py", line 71, in serve
-    await self._serve(sockets)
-  File "/usr/local/lib/python3.11/site-packages/uvicorn/server.py", line 78, in _serve
-    config.load()
-  File "/usr/local/lib/python3.11/site-packages/uvicorn/config.py", line 436, in load
-    self.loaded_app = import_from_string(self.app)
-                      ^^^^^^^^^^^^^^^^^^^^^^^^^^^^
-  File "/usr/local/lib/python3.11/site-packages/uvicorn/importer.py", line 19, in import_from_string
-    module = importlib.import_module(module_str)
-             ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^
-  File "/usr/local/lib/python3.11/importlib/__init__.py", line 126, in import_module
-    return _bootstrap._gcd_import(name[level:], package, level)
-           ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^
-  File "<frozen importlib._bootstrap>", line 1204, in _gcd_import
-  File "<frozen importlib._bootstrap>", line 1176, in _find_and_load
-  File "<frozen importlib._bootstrap>", line 1147, in _find_and_load_unlocked
-  File "<frozen importlib._bootstrap>", line 690, in _load_unlocked
-  File "<frozen importlib._bootstrap_external>", line 936, in exec_module
-  File "<frozen importlib._bootstrap_external>", line 1074, in get_code
-  File "<frozen importlib._bootstrap_external>", line 1004, in source_to_code
-  File "<frozen importlib._bootstrap>", line 241, in _call_with_frames_removed
-  File "/app/app.py", line 1
-    <PASTE YOUR WHOLE app.py CONTENT HERE EXACTLY>
-    ^
-SyntaxError: invalid syntax
-Traceback (most recent call last):
-  File "/usr/local/bin/uvicorn", line 8, in <module>
-    sys.exit(main())
-             ^^^^^^
-  File "/usr/local/lib/python3.11/site-packages/click/core.py", line 1442, in __call__
-    return self.main(*args, **kwargs)
-           ^^^^^^^^^^^^^^^^^^^^^^^^^^
-  File "/usr/local/lib/python3.11/site-packages/click/core.py", line 1363, in main
-    rv = self.invoke(ctx)
-         ^^^^^^^^^^^^^^^^
-  File "/usr/local/lib/python3.11/site-packages/click/core.py", line 1226, in invoke
-    return ctx.invoke(self.callback, **ctx.params)
-           ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^
-  File "/usr/local/lib/python3.11/site-packages/click/core.py", line 794, in invoke
-    return callback(*args, **kwargs)
-           ^^^^^^^^^^^^^^^^^^^^^^^^^
-  File "/usr/local/lib/python3.11/site-packages/uvicorn/main.py", line 413, in main
-    run(
-  File "/usr/local/lib/python3.11/site-packages/uvicorn/main.py", line 580, in run
-    server.run()
-  File "/usr/local/lib/python3.11/site-packages/uvicorn/server.py", line 67, in run
-    return asyncio.run(self.serve(sockets=sockets))
-           ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^
-  File "/usr/local/lib/python3.11/asyncio/runners.py", line 190, in run
-    return runner.run(main)
-           ^^^^^^^^^^^^^^^^
-  File "/usr/local/lib/python3.11/asyncio/runners.py", line 118, in run
-    return self._loop.run_until_complete(task)
-           ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^
-  File "/usr/local/lib/python3.11/asyncio/base_events.py", line 654, in run_until_complete
-    return future.result()
-           ^^^^^^^^^^^^^^^
-  File "/usr/local/lib/python3.11/site-packages/uvicorn/server.py", line 71, in serve
-    await self._serve(sockets)
-  File "/usr/local/lib/python3.11/site-packages/uvicorn/server.py", line 78, in _serve
-    config.load()
-  File "/usr/local/lib/python3.11/site-packages/uvicorn/config.py", line 436, in load
-    self.loaded_app = import_from_string(self.app)
-                      ^^^^^^^^^^^^^^^^^^^^^^^^^^^^
-  File "/usr/local/lib/python3.11/site-packages/uvicorn/importer.py", line 19, in import_from_string
-    module = importlib.import_module(module_str)
-             ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^
-  File "/usr/local/lib/python3.11/importlib/__init__.py", line 126, in import_module
-    return _bootstrap._gcd_import(name[level:], package, level)
-           ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^
-  File "<frozen importlib._bootstrap>", line 1204, in _gcd_import
-  File "<frozen importlib._bootstrap>", line 1176, in _find_and_load
-  File "<frozen importlib._bootstrap>", line 1147, in _find_and_load_unlocked
-  File "<frozen importlib._bootstrap>", line 690, in _load_unlocked
-  File "<frozen importlib._bootstrap_external>", line 936, in exec_module
-  File "<frozen importlib._bootstrap_external>", line 1074, in get_code
-  File "<frozen importlib._bootstrap_external>", line 1004, in source_to_code
-  File "<frozen importlib._bootstrap>", line 241, in _call_with_frames_removed
-  File "/app/app.py", line 1
-    <PASTE YOUR WHOLE app.py CONTENT HERE EXACTLY>
-    ^
-SyntaxError: invalid syntax
+from fastapi import FastAPI, Query
+from fastapi.middleware.cors import CORSMiddleware
+import httpx, asyncio, time, os, hashlib, json
+from typing import Dict, Any, Tuple, Optional, List
+from fastapi.responses import RedirectResponse, JSONResponse
+
+
+APP_NAME = "neuro-mechanism-backend"
+CALLER_ID = "neuro-mech-backend-demo"   # shows up in STRING logs
+
+app = FastAPI(title=APP_NAME)
+
+@app.get("/", include_in_schema=False)
+def root():
+    # Nice landing: send people to the interactive docs
+    return RedirectResponse(url="/docs")
+
+@app.get("/health", include_in_schema=False)
+def health():
+    return {"ok": True, "app": "neuro-mechanism-backend"}
+
+@app.get("/endpoints", include_in_schema=False)
+def endpoints():
+    return JSONResponse({
+        "GET": [
+            "/mechanism_graph?receptor=HTR2A&symptom=apathy",
+            "/heuristics/regions_from_string?receptor=HTR2A&limit=40",
+            "/lit/eupmc?query=HTR2A%20AND%20apathy&pageSize=5",
+            "/string/network?identifiers=HTR2A&species=9606",
+            "/gpcrdb/protein?entry=htr2a_human",
+            "/uniprot/search?query=HTR2A&size=5",
+            "/rxnav/rxcui?name=fluoxetine",
+            "/pubchem/compound_by_name?name=fluoxetine",
+            "/trials/search?q=HTR2A&pageSize=5",
+            "/health", "/docs"
+        ]
+    })
+
+app.add_middleware(
+    CORSMiddleware,
+    allow_origins=["*"], allow_credentials=True,
+    allow_methods=["*"], allow_headers=["*"]
+)
+
+UA = {"User-Agent": f"{APP_NAME}/1.1 (HF Space)"}
+
+# ----------------- NEW: tiny in-memory TTL cache -----------------
+class TTLCache:
+    def __init__(self, max_items=512):
+        self.store: Dict[str, Tuple[float, Any]] = {}
+        self.max_items = max_items
+        self._lock = asyncio.Lock()
+
+    def _mk(self, url: str, params: Optional[dict]) -> str:
+        key = url + "?" + (json.dumps(params, sort_keys=True) if params else "")
+        return hashlib.sha1(key.encode()).hexdigest()
+
+    async def get(self, url: str, params: Optional[dict], ttl: float):
+        k = self._mk(url, params)
+        async with self._lock:
+            item = self.store.get(k)
+            if item and (time.time() < item[0]):
+                return item[1]
+        async with httpx.AsyncClient(headers=UA, timeout=30) as client:
+            r = await client.get(url, params=params)
+            r.raise_for_status()
+            data = r.json()
+        async with self._lock:
+            if len(self.store) > self.max_items:
+                # drop an arbitrary item (good enough for a tiny Space)
+                self.store.pop(next(iter(self.store)))
+            self.store[k] = (time.time() + ttl, data)
+        return data
+
+CACHE = TTLCache()
+
+# ----------------- polite throttling for STRING ------------------
+_last_string_call = 0.0
+async def throttle_string():
+    """Be nice to STRING; ~1 req/sec as a courtesy."""
+    global _last_string_call
+    now = time.time()
+    wait = 1.05 - (now - _last_string_call)
+    if wait > 0:
+        await asyncio.sleep(wait)
+    _last_string_call = time.time()
+
+# ----------------- Helpers -----------------
+async def get_json_cached(url: str, params: dict, ttl: int):
+    return await CACHE.get(url, params, ttl)
+
+# ----------------- Existing endpoints ---------
+@app.get("/lit/eupmc")
+async def europe_pmc_search(query: str, pageSize: int = 5):
+    url = "https://www.ebi.ac.uk/europepmc/webservices/rest/search"
+    params = {"query": query, "format": "json", "pageSize": pageSize}
+    return await get_json_cached(url, params, ttl=600)
+
+@app.get("/lit/pubmed_esearch")
+async def pubmed_esearch(term: str, retmax: int = 10):
+    url = "https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi"
+    params = {"db":"pubmed","term":term,"retmode":"json","retmax":retmax}
+    return await get_json_cached(url, params, ttl=600)
+
+@app.get("/trials/search")
+async def ctgov_v2_studies(q: str, pageSize: int = 5):
+    url = "https://clinicaltrials.gov/api/v2/studies"
+    params = {"query.term": q, "pageSize": pageSize}
+    return await get_json_cached(url, params, ttl=900)
+
+@app.get("/rxnav/rxcui")
+async def rxnav_rxcui(name: str):
+    url = "https://rxnav.nlm.nih.gov/REST/rxcui.json"
+    params = {"name": name}
+    return await get_json_cached(url, params, ttl=86400)
+
+@app.get("/openfda/ae")
+async def openfda_adverse_events(drug: str, limit: int = 5):
+    url = "https://api.fda.gov/drug/event.json"
+    params = {"search": f'patient.drug.medicinalproduct:"{drug}"', "limit": limit}
+    return await get_json_cached(url, params, ttl=3600)
+
+@app.get("/pubchem/compound_by_name")
+async def pubchem_by_name(name: str):
+    url = f"https://pubchem.ncbi.nlm.nih.gov/rest/pug/compound/name/{name}/JSON"
+    return await get_json_cached(url, None, ttl=86400)
+
+@app.get("/uniprot/search")
+async def uniprot_search(query: str, size: int = 5):
+    url = "https://rest.uniprot.org/uniprotkb/search"
+    params = {"query": query, "format": "json", "size": size}
+    return await get_json_cached(url, params, ttl=86400)
+
+@app.get("/gpcrdb/protein")
+async def gpcrdb_protein(entry: str):
+    url = f"https://gpcrdb.org/services/protein/{entry}"
+    return await get_json_cached(url, None, ttl=86400)
+
+@app.get("/string/network")
+async def string_network(identifiers: str, species: int = 9606, limit: int = 50):
+    await throttle_string()
+    url = "https://string-db.org/api/json/network"
+    params = {"identifiers": identifiers, "species": species, "caller_identity": CALLER_ID, "limit": limit}
+    return await get_json_cached(url, params, ttl=3600)
+
+# ----------------- STRING → region heuristic -----------------
+REGION_TERMS_DEFAULT = [
+    "prefrontal cortex","anterior cingulate cortex","mPFC","ACC","nucleus accumbens","ventral striatum",
+    "dorsal striatum","caudate","putamen","amygdala","hippocampus","thalamus","hypothalamus",
+    "insula","VTA","substantia nigra","cerebellum"
+]
+
+async def eupmc_hitcount(q: str) -> int:
+    url = "https://www.ebi.ac.uk/europepmc/webservices/rest/search"
+    params = {"query": q, "format": "json", "pageSize": 0}
+    data = await get_json_cached(url, params, ttl=3600)
+    return int(data.get("hitCount", 0))
+
+def collect_gene_symbols_from_string(edges: List[dict], focus: str) -> List[str]:
+    genes = set()
+    f = focus.upper()
+    for e in edges:
+        for k in ("preferredName_A","preferredName_B"):
+            g = e.get(k)
+            if g and g.upper() != f:
+                genes.add(g)
+    return list(genes)
+
+@app.get("/heuristics/regions_from_string")
+async def regions_from_string(
+    receptor: str = Query(..., description="e.g., HTR2A"),
+    species: int = 9606,
+    limit: int = 40,
+    regions: Optional[str] = Query(None, description="comma-separated region terms; default common regions")
+):
+    """
+    Heuristic: rank brain regions by (STRING-weighted) literature co-occurrence.
+    """
+    # 1) STRING neighbors
+    edges = await string_network(receptor, species=species, limit=limit)
+    neighbors = collect_gene_symbols_from_string(edges, receptor)
+
+    # precompute STRING confidence per neighbor
+    conf: Dict[str, float] = {}
+    for e in edges:
+        a, b, score = e.get("preferredName_A"), e.get("preferredName_B"), float(e.get("score", 0))
+        if a and a.upper() != receptor.upper():
+            conf[a] = max(conf.get(a, 0.0), score)
+        if b and b.upper() != receptor.upper():
+            conf[b] = max(conf.get(b, 0.0), score)
+
+    region_list = [r.strip() for r in (regions.split(",") if regions else REGION_TERMS_DEFAULT) if r.strip()]
+    # 2) Europe PMC hitCount per region
+    gene_clause = " OR ".join([receptor] + neighbors[:25])  # cap size
+    tasks = []
+    for region in region_list:
+        q = f'("{region}") AND ({gene_clause})'
+        tasks.append(eupmc_hitcount(q))
+    counts = await asyncio.gather(*tasks)
+
+    # 3) Weighting
+    import math
+    mean_conf = sum(conf.values())/max(len(conf),1)
+    results = []
+    for region, hc in zip(region_list, counts):
+        score = (math.log10(hc+1.0)) * (mean_conf if conf else 0.2)
+        results.append({"region": region, "hits": hc, "weighted_score": round(score, 4)})
+
+    results.sort(key=lambda x: x["weighted_score"], reverse=True)
+    return {
+        "focus": receptor,
+        "neighbors_considered": neighbors[:25],
+        "regions_ranked": results,
+        "notes": "Exploratory heuristic using STRING neighbors + Europe PMC co-occurrence."
+    }
+
+# ----------------- Aggregator (adds region heuristic) --------
+@app.get("/mechanism_graph")
+async def mechanism_graph(
+    receptor: str = Query(..., description="e.g., HTR2A"),
+    species: int = 9606,
+    symptom: str = "apathy"
+):
+    gpcr_entry = f"{receptor.lower()}_human" if not receptor.lower().endswith("_human") else receptor.lower()
+
+    # cache-powered parallel fetches
+    gpcr = get_json_cached(f"https://gpcrdb.org/services/protein/{gpcr_entry}", None, ttl=86400)
+    string_net = get_json_cached("https://string-db.org/api/json/network",
+                                 {"identifiers": receptor, "species": species, "caller_identity": CALLER_ID, "limit": 50},
+                                 ttl=3600)
+    lit = get_json_cached("https://www.ebi.ac.uk/europepmc/webservices/rest/search",
+                          {"query": f"{receptor} AND {symptom}", "format": "json", "pageSize": 10},
+                          ttl=600)
+    # call our local async fn without FastAPI wrapper
+    region_scores = regions_from_string.__wrapped__(receptor=receptor, species=species, limit=40, regions=None)
+
+    gpcr_r, string_r, lit_r, regions_r = await asyncio.gather(gpcr, string_net, lit, region_scores)
+
+    return {
+        "receptor": receptor,
+        "gpcrdb": gpcr_r,
+        "string": string_r,
+        "literature": lit_r,
+        "region_scores": regions_r,
+        "notes": "Mechanism aggregator with cache + STRING→region heuristic"
+    }