prompt edits

backend/main.py

@@ -40,50 +40,85 @@ GROQ_MODEL   = "llama-3.3-70b-versatile"
 GROQ_API_KEY = os.environ.get("GROQ_API_KEY", "")
 
 # ── Prompts ───────────────────────────────────────────────────────────────────
-EXTRACTION_SYSTEM = """Extract protocol parameters from this research paper. Return ONLY valid JSON:
+EXTRACTION_SYSTEM = """You are an expert bioengineering methodologist. Extract ALL experimental protocol parameters from this research paper with maximum specificity. Return ONLY valid JSON:
 {
   "title": "paper title",
   "authors": "first author et al.",
   "year": "year",
-  "protocol_type": "e.g. Western blot / ELISA / PCR",
+  "protocol_type": "e.g. CRISPR screen / lentivirus production / protein purification",
   "parameters": {
-    "reagents": [{"name": "...", "concentration": "...", "vendor": "..."}],
-    "cell_lines": [{"name": "...", "culture_conditions": "...", "serum": "..."}],
+    "reagents": [{"name": "...", "concentration": "...", "volume": "...", "vendor": "...", "catalog": "..."}],
+    "cell_lines": [{"name": "...", "subtype": "e.g. HEK293 vs HEK293T", "culture_conditions": "...", "serum": "...", "passage": "...", "density_seeding": "..."}],
     "temperatures": [{"step": "...", "value": "...", "unit": "C"}],
-    "timings": [{"step": "...", "duration": "..."}],
-    "equipment": [{"name": "...", "settings": "..."}],
+    "timings": [{"step": "...", "duration": "...", "timepoint": "..."}],
+    "equipment": [{"name": "...", "settings": "...", "speed": "...", "duration": "..."}],
     "buffers": [{"name": "...", "composition": "...", "pH": "..."}],
     "antibodies": [{"target": "...", "dilution": "...", "vendor": "..."}],
+    "viral_production": [{"parameter": "...", "value": "...", "notes": "..."}],
+    "transfection": [{"reagent": "...", "ratio": "...", "volume": "...", "timing": "..."}],
+    "selection": [{"agent": "...", "concentration": "...", "duration": "..."}],
+    "moi": [{"value": "...", "cell_line": "...", "context": "..."}],
+    "library_coverage": [{"cells_per_sgrna": "...", "total_cells": "...", "replicates": "..."}],
+    "analysis_pipeline": [{"tool": "...", "version": "...", "parameters": "...", "statistical_model": "..."}],
+    "packaging_system": [{"generation": "2nd or 3rd", "plasmids": "...", "ratios": "...", "promoter": "..."}],
+    "centrifugation": [{"step": "...", "speed": "...", "duration": "...", "temperature": "..."}],
     "other": [{"parameter": "...", "value": "..."}]
   }
-}"""
+}
 
-COMPARISON_SYSTEM = """You are an expert in bioengineering reproducibility and experimental methodology.
-Compare protocols from multiple research papers and identify ALL methodological contradictions.
-Return ONLY valid JSON (no markdown fences, no extra text) using this schema:
+IMPORTANT RULES:
+- If a value is not stated, write "Not specified" — never omit the field
+- Extract exact numerical values (e.g. "0.3 MOI", "500 cells/sgRNA", "72h") not vague descriptions
+- For cell lines, always note whether it is HEK293 or HEK293T — these are biologically distinct
+- For lentivirus production, extract packaging plasmid names, ratios, and generation (2nd vs 3rd)
+- For CRISPR screens, always look for: MOI, library coverage, selection agent/duration, readout method, analysis software
+- For protein expression, always look for: induction conditions (IPTG concentration, OD600, temperature), purification steps, elution conditions"""
+
+COMPARISON_SYSTEM = """You are a senior peer reviewer specializing in bioengineering reproducibility. 
+Your job is to identify ALL methodological contradictions between protocols — including subtle ones most researchers miss.
+
+Return ONLY valid JSON (no markdown, no extra text):
 {
   "protocol_type": "detected protocol type",
   "contradictions": [
     {
       "parameter": "parameter name",
-      "category": "reagents|cell_lines|temperatures|timings|equipment|buffers|antibodies|other",
+      "category": "reagents|cell_lines|temperatures|timings|equipment|buffers|viral_production|transfection|selection|moi|library_coverage|analysis_pipeline|packaging_system|centrifugation|other",
       "severity": "high|medium|low",
-      "values": {"paper_0": "value from paper 1", "paper_1": "value from paper 2"},
-      "explanation": "why this is a contradiction and its likely impact on reproducibility"
+      "values": {"paper_0": "exact value from paper 1", "paper_1": "exact value from paper 2"},
+      "explanation": "specific biological mechanism by which this difference affects reproducibility — cite exact parameter values, not vague descriptions"
     }
   ],
   "ranked_issues": [
-    {"rank": 1, "parameter": "...", "severity": "high|medium|low", "brief": "one-sentence impact"}
+    {"rank": 1, "parameter": "...", "severity": "high|medium|low", "brief": "one-sentence mechanistic impact — must mention specific values"}
   ],
   "optimal_protocol": {
     "rationale": "overall recommendation rationale",
     "parameters": [
-      {"label": "parameter name", "value": "recommended value", "reason": "why this is optimal"}
+      {"label": "parameter name", "value": "recommended value", "reason": "cite evidence from papers or established literature for why this value is optimal"}
     ]
   },
   "summary": {"total_contradictions": 0, "high": 0, "medium": 0, "low": 0}
-}"""
-
+}
+
+SEVERITY RULES:
+- HIGH: affects primary experimental outcome (e.g. MOI determines single vs multiple sgRNA integration; HEK293 vs HEK293T affects viral titer 3-10x; selection duration creates fitness bias)
+- MEDIUM: affects data quality or efficiency (e.g. library coverage affects statistical power; packaging ratios affect titer)
+- LOW: minor procedural difference unlikely to change conclusions
+
+CRITICAL CHECKS — always look for these specific contradictions:
+1. HEK293 vs HEK293T (SV40 T antigen affects transfection efficiency and episomal replication)
+2. MOI values — flag if one paper uses <0.5 (single integration) vs ≥0.5 (multiple integrations)
+3. Library coverage — flag if cells/sgRNA differ by more than 2x
+4. Selection duration — longer selection introduces fitness bias toward fast-growing cells
+5. Antibiotic concentration differences (e.g. puromycin 1 vs 2 µg/mL)
+6. 2nd vs 3rd generation lentiviral packaging (biosafety and titer implications)
+7. Analysis pipeline (casTLE vs MAGeCK vs BAGEL use different statistical models — hits may not overlap)
+8. Viral collection timepoints (36h+60h dual collection vs single 72h — affects titer and tropism)
+9. Centrifugation concentration vs filter-only (ultracentrifugation vs 0.45µm filter)
+10. Promoter differences (CMV vs EF1a vs PGK — expression level and cell-type specificity differ)
+
+DO NOT flag as a contradiction: parameters where both papers say "Not specified" — these are shared gaps, not contradictions. Flag them separately as reproducibility gaps only if they are critical parameters."""
 # ── Core helpers ──────────────────────────────────────────────────────────────
 
 def extract_text_from_pdf(pdf_path: str) -> str: