File size: 12,257 Bytes
db32e07
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119
120
121
122
123
124
125
126
127
128
129
130
131
132
133
134
135
136
137
138
139
140
141
142
143
144
145
146
147
148
149
150
151
152
153
154
155
156
157
158
159
160
161
162
163
164
165
166
167
168
169
170
171
172
173
174
175
176
177
178
179
180
181
182
183
184
185
186
187
188
189
190
191
192
193
194
195
196
197
198
199
200
201
202
203
204
205
206
207
208
209
210
211
212
213
214
215
216
217
218
219
220
221
222
223
224
225
226
227
228
229
230
231
232
233
234
235
236
237
238
239
240
241
242
243
244
245
246
247
248
249
250
251
252
253
254
255
256
257
258
259
260
261
262
263
264
265
266
267
268
269
270
271
272
273
274
275
276
277
278
279
280
281
282
283
284
285
286
287
288
289
290
291
292
293
294
295
296
297
298
299
300
301
302
303
304
305
306
307
308
309
310
311
312
313
314
315
316
317
318
319
320
321
322
323
324
325
326
327
328
329
330
331
332
333
334
335
336
337
338
339
340
341
342
343
344
345
346
347
348
349
#!/usr/bin/env python
"""
Prepare fine-tuning data for Spec-Agent from RAG dataset.

This script converts the RAG dataset into a format suitable for fine-tuning
Llama-3 on molecular structure prediction tasks.
"""
from __future__ import annotations

import argparse
import json
import sys
from pathlib import Path
from typing import List, Dict, Any

ROOT = Path(__file__).resolve().parents[1]
if str(ROOT) not in sys.path:
    sys.path.insert(0, str(ROOT))

from spec_rag.io import load_embeddings, load_smiles
from spec_rag.faiss_index import load_index
from spec_rag.retrieval import search_index


def parse_args() -> argparse.Namespace:
    parser = argparse.ArgumentParser(description="Prepare fine-tuning data for Spec-Agent")
    parser.add_argument(
        "--train-jsonl",
        type=Path,
        required=True,
        help="Training JSONL file (from build_rag_dataset.py)",
    )
    parser.add_argument(
        "--spec-embeddings",
        type=Path,
        help="Path to spectrum embeddings .npy file (only needed if RAG context not in input_text)",
    )
    parser.add_argument(
        "--faiss-index",
        type=Path,
        help="Path to FAISS index directory (only needed if RAG context not in input_text)",
    )
    parser.add_argument(
        "--smiles-path",
        type=Path,
        help="Path to SMILES file used for indexing (only needed if RAG context not in input_text)",
    )
    parser.add_argument(
        "--mgf-path",
        type=Path,
        help="Path to MGF file for extracting peaks",
    )
    parser.add_argument(
        "--output-jsonl",
        type=Path,
        required=True,
        help="Output JSONL file for fine-tuning",
    )
    parser.add_argument(
        "--top-k",
        type=int,
        default=5,
        help="Number of RAG references to include (default: 5)",
    )
    parser.add_argument(
        "--max-examples",
        type=int,
        help="Maximum number of examples to process (for testing)",
    )
    return parser.parse_args()


def load_all_mgf_peaks(mgf_path: Path) -> Dict[int, List[tuple[float, float]]]:
    """Load all spectrum peaks from MGF file into memory (indexed by spectrum index)."""
    peaks_dict = {}
    
    print(f"Loading all peaks from MGF file: {mgf_path}")
    with open(mgf_path, "r") as f:
        spec_count = -1
        current_peaks = []
        in_spec = False
        
        for line in f:
            line_stripped = line.strip()
            if line_stripped.startswith("BEGIN IONS"):
                # Save previous spectrum if exists
                if in_spec and current_peaks:
                    peaks_dict[spec_count] = sorted(current_peaks, key=lambda x: x[1], reverse=True)
                spec_count += 1
                in_spec = True
                current_peaks = []
            elif in_spec:
                if line_stripped.startswith("END IONS"):
                    if current_peaks:
                        peaks_dict[spec_count] = sorted(current_peaks, key=lambda x: x[1], reverse=True)
                    in_spec = False
                    current_peaks = []
                elif line_stripped and not line_stripped.startswith(("PEPMASS", "CHARGE", "RTINSECONDS", "TITLE", "SCANS", "NAME", "SMILES", "INCHIKEY", "FORMULA", "PRECURSOR", "ADDUCT", "INSTRUMENT", "COLLISION", "FOLD", "SIMULATION")):
                    parts = line_stripped.split()
                    if len(parts) >= 2:
                        try:
                            mz = float(parts[0])
                            intensity = float(parts[1])
                            if intensity > 0:
                                current_peaks.append((mz, intensity))
                        except ValueError:
                            continue
        
        # Handle last spectrum if file doesn't end with END IONS
        if in_spec and current_peaks:
            peaks_dict[spec_count] = sorted(current_peaks, key=lambda x: x[1], reverse=True)
    
    print(f"Loaded {len(peaks_dict)} spectra from MGF file")
    return peaks_dict


def calculate_target_mass(smiles: str) -> float | None:
    """Calculate molecular mass from SMILES."""
    try:
        from rdkit import Chem
        from rdkit.Chem import Descriptors
        mol = Chem.MolFromSmiles(smiles)
        if mol:
            return Descriptors.ExactMolWt(mol)
    except:
        pass
    return None


def build_finetune_prompt(
    spectrum_peaks: List[tuple[float, float]] | None,
    rag_context: List[str],
    target_mass: float | None,
    target_smiles: str,
) -> Dict[str, Any]:
    """Build a fine-tuning prompt in chat format."""
    
    # Build system message
    system_content = """You are an expert mass spectrometrist and computational chemist specializing in de novo molecular structure elucidation from mass spectrometry data.

TASK: Predict the complete molecular structure (SMILES) from mass spectrum data.

CRITICAL REQUIREMENTS:
1. Generate COMPLEX molecules (30-100 atoms), NOT simple molecules
2. Use reference molecules as structural templates
3. Match target molecular mass within 10 Da
4. Output ONLY valid SMILES strings

WORKFLOW:
1. Analyze target mass to estimate atom count
2. Select best reference molecule as template
3. Modify template to match target mass
4. Validate structure"""
    
    # Build user message
    user_parts = []
    
    if target_mass:
        estimated_atoms = int(target_mass / 14)
        user_parts.append(f"Target molecular mass: {target_mass:.4f} Da (estimated {estimated_atoms} atoms)")
    
    if spectrum_peaks and len(spectrum_peaks) > 0:
        peaks_str = ', '.join(f'{mz:.2f} (intensity: {intensity:.3f})' for mz, intensity in spectrum_peaks[:20])
        user_parts.append(f"Major spectrum peaks (m/z with intensity): {peaks_str}")
    
    if rag_context:
        user_parts.append("\nReference molecules (structural templates):")
        for i, smiles in enumerate(rag_context[:5], 1):
            user_parts.append(f"  {i}. {smiles}")
        user_parts.append("\nPredict the molecular structure (SMILES) matching the target mass.")
    
    user_content = "\n".join(user_parts)
    
    # Assistant response
    assistant_content = target_smiles
    
    return {
        "messages": [
            {"role": "system", "content": system_content},
            {"role": "user", "content": user_content},
            {"role": "assistant", "content": assistant_content},
        ]
    }


def extract_rag_context_from_input(input_text: str) -> List[str]:
    """Extract RAG context SMILES from input_text field."""
    import re
    rag_smiles = []
    
    # Try to extract from "Context: Reference Molecules: [...]" format
    if "Context: Reference Molecules:" in input_text:
        context_part = input_text.split("Context: Reference Molecules:")[1]
        if "Target:" in context_part:
            context_part = context_part.split("Target:")[0]
        
        # Extract SMILES from [SMILES] format
        smiles_pattern = r'\[([^\]]+)\]'
        matches = re.findall(smiles_pattern, context_part)
        rag_smiles = [s.strip() for s in matches if s.strip()]
    
    return rag_smiles


def main() -> None:
    args = parse_args()
    
    # Load data
    print("Loading data...")
    train_data = []
    with open(args.train_jsonl, "r") as f:
        for line in f:
            if line.strip():
                train_data.append(json.loads(line))
    
    if args.max_examples:
        train_data = train_data[:args.max_examples]
    
    print(f"Loaded {len(train_data)} training examples")
    
    # Check if we need to retrieve RAG context or extract from input_text
    use_existing_context = False
    if train_data and "input_text" in train_data[0]:
        # Check if input_text contains RAG context
        sample_input = train_data[0].get("input_text", "")
        if "Context: Reference Molecules:" in sample_input:
            use_existing_context = True
            print("Found RAG context in input_text, will extract directly (no need to retrieve)")
        else:
            print("No RAG context in input_text, will retrieve from index")
    
    # Load index only if we need to retrieve
    index = None
    smiles_list = None
    spec_embeddings = None
    
    if not use_existing_context:
        print("Loading embeddings and index for retrieval...")
        spec_embeddings = load_embeddings(args.spec_embeddings)
        
        # Find FAISS index file
        index_path = Path(args.faiss_index)
        index_file = None
        if index_path.is_dir():
            # Try different possible file names
            for name in ["smiles.index", "index.faiss", "index", "faiss.index"]:
                candidate = index_path / name
                if candidate.exists():
                    index_file = candidate
                    break
            if index_file is None:
                available = list(index_path.glob("*"))
                raise FileNotFoundError(
                    f"Could not find FAISS index in {index_path}. "
                    f"Available files: {[f.name for f in available]}"
                )
        else:
            index_file = index_path
        
        index = load_index(index_file)
        smiles_list = load_smiles(args.smiles_path)
        
        print(f"Index has {index.ntotal} vectors")
        print(f"SMILES list has {len(smiles_list)} molecules")
    
    # Pre-load all MGF peaks if MGF path is provided
    mgf_peaks_dict = {}
    if args.mgf_path:
        mgf_peaks_dict = load_all_mgf_peaks(args.mgf_path)
    
    # Process examples
    finetune_examples = []
    
    for i, example in enumerate(train_data):
        if i % 1000 == 0:
            print(f"Processing example {i}/{len(train_data)}... ({len(finetune_examples)} created so far)")
        
        spectrum_id = example.get("spectrum_id", str(i))
        target_smiles = example.get("target_text", "")
        input_text = example.get("input_text", "")
        
        if not target_smiles:
            continue
        
        # Calculate target mass
        target_mass = calculate_target_mass(target_smiles)
        if not target_mass:
            continue
        
        # Get RAG context
        rag_smiles = []
        if use_existing_context:
            # Extract from input_text
            rag_smiles = extract_rag_context_from_input(input_text)
            if not rag_smiles:
                continue
            # Limit to top_k
            rag_smiles = rag_smiles[:args.top_k]
        else:
            # Retrieve from index
            try:
                spec_idx = int(spectrum_id)
                if spec_idx >= len(spec_embeddings):
                    continue
                
                query_embedding = spec_embeddings[spec_idx:spec_idx+1]
                scores, indices = search_index(index, query_embedding, k=args.top_k)
                
                for idx_row in indices:
                    for idx in idx_row:
                        if 0 <= idx < len(smiles_list):
                            rag_smiles.append(smiles_list[idx])
                
                if not rag_smiles:
                    continue
            except (ValueError, IndexError):
                continue
        
        # Get spectrum peaks from pre-loaded dict
        spectrum_peaks = None
        if mgf_peaks_dict:
            try:
                spec_idx = int(spectrum_id)
                spectrum_peaks = mgf_peaks_dict.get(spec_idx)
            except (ValueError, IndexError):
                pass
        
        # Build fine-tuning example
        finetune_example = build_finetune_prompt(
            spectrum_peaks=spectrum_peaks,
            rag_context=rag_smiles,
            target_mass=target_mass,
            target_smiles=target_smiles,
        )
        
        finetune_examples.append(finetune_example)
    
    # Save fine-tuning data
    print(f"\nSaving {len(finetune_examples)} fine-tuning examples to {args.output_jsonl}...")
    with open(args.output_jsonl, "w") as f:
        for example in finetune_examples:
            f.write(json.dumps(example) + "\n")
    
    print(f"Done! Created {len(finetune_examples)} fine-tuning examples.")


if __name__ == "__main__":
    main()