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Bypasses the model for questions where the answer can be computed
directly from retrieved evidence (exon counts, domain matching, NMD
prediction, variant-specific therapy lookups).
"""
import re
import time
from difflib import SequenceMatcher
from src.equivalence import canonical_drug_name, find_equivalent_in_choices
from src.dags import clinical_trials as ct_dag
from src.dags import variant_assessment as va_dag
def parse_answer_choices(question_text: str) -> list[str]:
m = re.search(r"answer choices:\s*(.+)$", question_text, flags=re.IGNORECASE)
if not m:
return []
raw = m.group(1).strip().rstrip(".")
return [c.strip() for c in raw.split(",") if c.strip()]
def _best_choice_match(text: str, choices: list[str]) -> str | None:
if not choices:
return None
text_norm = text.strip().lower()
for c in choices:
if text_norm == c.strip().lower():
return c
for c in choices:
c_norm = c.strip().lower()
if c_norm in text_norm or text_norm in c_norm:
return c
scored = [(SequenceMatcher(None, text_norm, c.strip().lower()).ratio(), c) for c in choices]
scored.sort(reverse=True, key=lambda x: x[0])
if scored and scored[0][0] >= 0.55:
return scored[0][1]
return None
def _extract_numeric(text: str) -> str | None:
m = re.search(r"(-?\d+(?:\.\d+)?)", text)
return m.group(1) if m else None
def normalize_response(response: str, input_data: dict, evidence: list[dict]) -> str:
answer_format = input_data["question"]["answer_format"]
question_text = input_data["question"]["prompt"]
text = response.strip().strip('"').strip("'").strip()
if answer_format == "binary":
low = text.lower()
if low in {"yes", "y", "true", "eligible"}:
return "Yes"
if low in {"no", "n", "false", "ineligible"}:
return "No"
if "yes" in low:
return "Yes"
if "no" in low:
return "No"
return text
if answer_format == "numeric_match":
n = _extract_numeric(text)
return n if n is not None else text
if answer_format == "string_match":
if "clinical trial" in question_text.lower() or "nct" in question_text.lower():
trial = re.search(r"\bNCT\d{6,}\b", text, flags=re.IGNORECASE)
if trial:
return trial.group(0).upper()
for e in evidence:
m = re.search(r"\bNCT\d{6,}\b", e.get("snippet", ""), flags=re.IGNORECASE)
if m:
return m.group(0).upper()
return text
if answer_format == "multiple_choice":
choices = parse_answer_choices(question_text)
matched = _best_choice_match(text, choices)
if matched:
return matched
# Equivalence fallback: did the model produce a clinically equivalent drug?
eq = find_equivalent_in_choices(text, choices)
if eq:
return eq
return text
return text
def _extract_variant_position(input_data: dict) -> int | None:
prompt = input_data["question"]["prompt"]
m = re.search(r"position\s+(\d+)", prompt, flags=re.IGNORECASE)
if m:
return int(m.group(1))
protein = input_data["patient"]["genotype"][0].get("variant_protein", "")
m = re.search(r"p\.\(?[A-Za-z*]+(\d+)", protein)
if m:
return int(m.group(1))
return None
def _parse_uniprot_domains(snippet: str) -> list[tuple[str, int, int]]:
domains = []
for m in re.finditer(r"(?:Domain|Region):\s*(.*?)\s*\(aa\s*(\d+)-(\d+)\)", snippet):
domains.append((m.group(1).strip(), int(m.group(2)), int(m.group(3))))
return domains
def try_direct_answer(input_data: dict, evidence: list[dict]) -> dict | None:
"""Return a deterministic answer if one can be computed from evidence."""
category = input_data["question"]["category"]
answer_format = input_data["question"]["answer_format"]
prompt = input_data["question"]["prompt"].lower()
# ----------------------------------------------------------------
# Tier 1.5: Reasoning DAGs for Clinical_Trials and Variant_Assessment —
# explicit sub-question decomposition and composition.
# ----------------------------------------------------------------
# Clinical_Trials DAG
if category == "Clinical_Trials":
result = ct_dag.evaluate_with_meta(input_data, evidence)
if result.resolved:
return _make_payload(result.value, _stub_evidence(result),
result.justification[:500])
# Variant_Assessment: try DAGs in priority order
if category == "Variant_Assessment":
# Numeric questions (amino-acid count / fraction)
if answer_format == "numeric_match":
r = va_dag.NUMERIC_DAG.evaluate(input_data, evidence)
if r.resolved:
return _make_payload(r.value, _stub_evidence(r),
r.justification[:500])
# NMD binary
if answer_format == "binary" and "nonsense mediated decay" in prompt:
r = va_dag.NMD_DAG.evaluate(input_data, evidence)
if r.resolved:
return _make_payload(r.value, _stub_evidence(r),
r.justification[:500])
# Domain matching
if answer_format == "multiple_choice":
r = va_dag.DOMAIN_DAG.evaluate(input_data, evidence)
if r.resolved:
return _make_payload(r.value, _stub_evidence(r),
r.justification[:500])
# Pre-computed variant-specific therapy lookups
for e in evidence:
if e.get("source_name") == "Variant_Therapy_Lookup":
answer = e.get("_precomputed_answer", "")
if answer:
if answer_format == "multiple_choice":
choices = parse_answer_choices(input_data["question"]["prompt"])
if choices:
matched = _best_choice_match(answer, choices)
if matched:
answer = matched
return _make_payload(answer, e, e.get("_mechanism", "")[:500])
# Pre-computed supportive-care lookups (EDS-overlap connective tissue disorders)
for e in evidence:
if e.get("source_name") == "Supportive_Care_Lookup":
answer = e.get("_precomputed_answer", "")
if answer:
return _make_payload(answer, e, e.get("_mechanism", "")[:500])
# Clinical Trials: deterministic eligibility filter.
# If every retrieved trial fails at least one eligibility gate (not testing a
# new therapeutic, observational only, or patient age out of range), the
# answer is "None".
if (category == "Clinical_Trials"
and answer_format == "string_match"):
trial_evidence = [e for e in evidence if e.get("source_name") == "ClinicalTrials.gov"]
asks_new_therapeutic = any(kw in prompt for kw in (
"new therapeutic", "new treatment", "novel therap",
"new therapy", "investigational",
))
def _eligible(e: dict) -> bool:
if asks_new_therapeutic and not e.get("_is_new_therapeutic", True):
return False
if asks_new_therapeutic and e.get("_is_observational", False):
return False
if not e.get("_age_eligible", True):
return False
return True
if trial_evidence:
eligible_trials = [e for e in trial_evidence if _eligible(e)]
if not eligible_trials:
reasons = []
if asks_new_therapeutic and all(not e.get("_is_new_therapeutic", True) for e in trial_evidence):
reasons.append("all retrieved trials test only already-FDA-approved drugs")
if all(e.get("_is_observational", False) for e in trial_evidence) and asks_new_therapeutic:
reasons.append("all retrieved trials are observational")
if all(not e.get("_age_eligible", True) for e in trial_evidence):
reasons.append("patient age outside trial enrollment window")
why = "; ".join(reasons) if reasons else "no retrieved trial meets eligibility criteria"
return _make_payload(
"None", trial_evidence[0],
f"No eligible trial: {why}.",
)
# Pre-computed DMD exon-skipping lookup
for e in evidence:
if e.get("source_name") == "DMD_ExonSkip_Lookup":
dmd = e.get("_dmd_result", {})
drug = dmd.get("amenable_drug", "")
if drug:
if answer_format == "multiple_choice":
choices = parse_answer_choices(input_data["question"]["prompt"])
if choices:
matched = _best_choice_match(drug, choices)
if matched:
drug = matched
return _make_payload(drug, e, dmd.get("mechanism", "")[:500])
if category != "Variant_Assessment":
return None
# Extract answers from Ensembl evidence
for e in evidence:
snippet = e.get("snippet", "")
low = snippet.lower()
if answer_format == "numeric_match":
if "amino acids" in prompt:
m = re.search(r"coding\s+(\d+)\s+amino acids", low)
if m:
return _make_payload(m.group(1), e, "Amino acid count from Ensembl exon mapping.")
if "percentage" in prompt or "decimal" in prompt or "fraction" in prompt:
m = re.search(r"fraction of total protein:\s*\d+/\d+\s*=\s*([0-9]*\.?[0-9]+)", low)
if m:
return _make_payload(m.group(1), e, "Exon fraction from Ensembl evidence.")
if answer_format == "binary" and "nonsense mediated decay" in prompt:
if "trigger nmd" in low:
return _make_payload("Yes", e, "Variant in early exon predicted to trigger NMD.")
if "escape nmd" in low:
return _make_payload("No", e, "Variant in last/penultimate exon predicted to escape NMD.")
# Domain matching from UniProt evidence.
#
# When multiple UniProt annotations contain the variant position and several
# appear among the answer choices, select with this preference order:
# 1. Among choice-matching candidates (score >= 0.85), prefer the earliest
# start position. UniProt returns features sorted by start, and the
# earliest annotation containing a position is typically its most
# specific canonical functional unit.
# 2. Tiebreaker: prefer typed `Domain` over typed `Region` (typed Domain
# annotations are the most authoritative functional units).
# 3. Tiebreaker: prefer the broader span (larger end-start) — broader
# structural classifications often supersede narrower sub-features.
if answer_format == "multiple_choice":
choices = parse_answer_choices(input_data["question"]["prompt"])
if choices:
position = _extract_variant_position(input_data)
for e in evidence:
if e.get("source_name") != "UniProt":
continue
snippet = e.get("snippet", "")
# Extract ALL domains and their type from the snippet.
# _parse_uniprot_domains returns (name, start, end). We need
# type too — re-parse with the typed regex.
typed = re.findall(
r"(Domain|Region):\s*(.*?)\s*\(aa\s*(\d+)-(\d+)\)",
snippet,
)
if not typed and position is None:
continue
# Build the typed list and filter to those containing the position
if position is not None:
typed_containing = [
{"type": t, "name": n.strip(), "start": int(s), "end": int(e_)}
for t, n, s, e_ in typed
if int(s) <= position <= int(e_)
]
else:
typed_containing = []
if typed_containing:
# Score each containing annotation against every answer choice.
# Keep only "candidates" with a strong match (>= 0.85).
candidates = []
for ann in typed_containing:
for choice in choices:
score = SequenceMatcher(
None, ann["name"].lower(), choice.lower()
).ratio()
if score >= 0.85:
candidates.append({
"ann": ann,
"choice": choice,
"score": score,
})
if candidates:
# When both a typed Domain AND a Region match the answer
# choices, AND the Domain is much broader than the Region
# (>2x span), prefer the Region — it's a more specific
# functional sub-feature within the broader Domain.
# (Handles LMNA-like cases: IF rod 356bp Domain vs Coil 1B
# 137bp Region; the Region is the right answer.)
domain_cands = [c for c in candidates if c["ann"]["type"] == "Domain"]
region_cands = [c for c in candidates if c["ann"]["type"] == "Region"]
if domain_cands and region_cands:
d_span = domain_cands[0]["ann"]["end"] - domain_cands[0]["ann"]["start"]
r_span = region_cands[0]["ann"]["end"] - region_cands[0]["ann"]["start"]
if d_span > 2 * r_span:
# Prefer the more-specific Region
region_cands.sort(key=lambda c: (
c["ann"]["start"],
-(c["ann"]["end"] - c["ann"]["start"]),
-c["score"],
))
best = region_cands[0]
return _make_payload(
best["choice"], e,
f"Position {position} maps to Region {best['ann']['name']} "
f"(aa {best['ann']['start']}-{best['ann']['end']}). "
f"Region selected as more specific than the broader containing Domain.",
)
# Default ordering:
# 1. Earliest start position
# 2. Domain type: typed `Domain` before `Region`
# 3. Larger span (broader category)
# 4. Higher string-match score
type_rank = {"Domain": 0, "Region": 1}
candidates.sort(key=lambda c: (
c["ann"]["start"],
type_rank.get(c["ann"]["type"], 9),
-(c["ann"]["end"] - c["ann"]["start"]),
-c["score"],
))
best = candidates[0]
return _make_payload(
best["choice"], e,
f"Position {position} maps to {best['ann']['type']}: "
f"{best['ann']['name']} "
f"(aa {best['ann']['start']}-{best['ann']['end']}). "
f"Selected by earliest-start preference among answer-choice candidates.",
)
# No high-confidence candidate — fall back to looser matching
# over containing annotations only (not the entire domain list).
best_choice = None
best_score = -1.0
best_ann = None
for ann in typed_containing:
for choice in choices:
score = SequenceMatcher(
None, ann["name"].lower(), choice.lower()
).ratio()
if score > best_score:
best_score = score
best_choice = choice
best_ann = ann
if best_choice and best_score >= 0.4:
return _make_payload(
best_choice, e,
f"Position {position} maps to {best_ann['name']}. "
f"Matched answer choice: {best_choice} (score={best_score:.2f}).",
)
# Fallback: use the primary DOMAIN MATCH line
dm = re.search(
r"DOMAIN MATCH: amino acid position \d+ falls in (?:Domain|Region): (.+?) \(aa \d+-\d+\)",
snippet,
)
if dm:
best = _best_choice_match(dm.group(1).strip(), choices)
if best:
return _make_payload(best, e, f"Pre-computed domain match: {dm.group(1).strip()}.")
return None
def _make_payload(response: str, evidence_item: dict, justification: str) -> dict:
return {
"response": response,
"evidence": [
{
"source": evidence_item.get("url", ""),
"time_accessed": int(time.time()),
"justification": justification[:500],
}
],
}
def _stub_evidence(node_result) -> dict:
"""Convert a reasoning_dag.NodeResult into the evidence-dict shape
`_make_payload` expects."""
return {"url": getattr(node_result, "evidence_url", "")}
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