File size: 27,395 Bytes
e4183cf
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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
350
351
352
353
354
355
356
357
358
359
360
361
362
363
364
365
366
367
368
369
370
371
372
373
374
375
376
377
378
379
380
381
382
383
384
385
386
387
388
389
390
391
392
393
394
395
396
397
398
399
400
401
402
403
404
405
406
407
408
409
410
411
412
413
414
415
416
417
418
419
420
421
422
423
424
425
426
427
428
429
430
431
432
433
434
435
436
437
438
439
440
441
442
443
444
445
446
447
448
449
450
451
452
453
454
455
456
457
458
459
460
461
462
463
464
465
466
467
468
469
470
471
472
473
474
475
476
477
478
479
480
481
482
483
484
485
486
487
488
489
490
491
492
493
494
495
496
497
498
499
500
501
502
503
504
505
506
507
508
509
510
511
512
513
514
515
516
517
518
519
520
521
522
523
524
525
526
527
528
529
530
531
532
533
534
535
536
537
538
539
540
541
542
543
544
545
546
547
548
549
550
551
552
553
554
555
556
557
558
559
560
561
562
563
564
565
566
567
568
569
570
571
572
573
574
575
576
577
578
579
580
581
582
583
584
585
586
587
588
589
590
591
592
593
594
595
596
597
598
599
600
601
602
603
604
605
606
607
608
609
610
611
612
613
614
615
616
617
618
619
620
621
622
623
624
625
626
627
628
629
630
631
632
633
634
635
636
637
638
639
640
641
642
643
644
645
646
647
648
649
650
651
652
653
654
655
656
657
658
659
660
661
662
663
664
665
666
667
668
669
670
671
672
673
674
675
676
677
678
679
680
681
682
683
684
685
686
{
 "cells": [
  {
   "cell_type": "code",
   "execution_count": null,
   "id": "ef013425",
   "metadata": {},
   "outputs": [],
   "source": [
    "import sys\n",
    "import os\n",
    "sys.path.append(os.path.abspath(os.path.join(os.getcwd(), '../..')))\n",
    "\n",
    "# Path Configuration\n",
    "from tools.preprocess import *\n",
    "\n",
    "# Processing context\n",
    "trait = \"Craniosynostosis\"\n",
    "cohort = \"GSE27976\"\n",
    "\n",
    "# Input paths\n",
    "in_trait_dir = \"../../input/GEO/Craniosynostosis\"\n",
    "in_cohort_dir = \"../../input/GEO/Craniosynostosis/GSE27976\"\n",
    "\n",
    "# Output paths\n",
    "out_data_file = \"../../output/preprocess/Craniosynostosis/GSE27976.csv\"\n",
    "out_gene_data_file = \"../../output/preprocess/Craniosynostosis/gene_data/GSE27976.csv\"\n",
    "out_clinical_data_file = \"../../output/preprocess/Craniosynostosis/clinical_data/GSE27976.csv\"\n",
    "json_path = \"../../output/preprocess/Craniosynostosis/cohort_info.json\"\n"
   ]
  },
  {
   "cell_type": "markdown",
   "id": "e419df3c",
   "metadata": {},
   "source": [
    "### Step 1: Initial Data Loading"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "id": "d9cf9152",
   "metadata": {},
   "outputs": [],
   "source": [
    "from tools.preprocess import *\n",
    "# 1. Identify the paths to the SOFT file and the matrix file\n",
    "soft_file, matrix_file = geo_get_relevant_filepaths(in_cohort_dir)\n",
    "\n",
    "# 2. Read the matrix file to obtain background information and sample characteristics data\n",
    "background_prefixes = ['!Series_title', '!Series_summary', '!Series_overall_design']\n",
    "clinical_prefixes = ['!Sample_geo_accession', '!Sample_characteristics_ch1']\n",
    "background_info, clinical_data = get_background_and_clinical_data(matrix_file, background_prefixes, clinical_prefixes)\n",
    "\n",
    "# 3. Obtain the sample characteristics dictionary from the clinical dataframe\n",
    "sample_characteristics_dict = get_unique_values_by_row(clinical_data)\n",
    "\n",
    "# 4. Explicitly print out all the background information and the sample characteristics dictionary\n",
    "print(\"Background Information:\")\n",
    "print(background_info)\n",
    "print(\"Sample Characteristics Dictionary:\")\n",
    "print(sample_characteristics_dict)\n"
   ]
  },
  {
   "cell_type": "markdown",
   "id": "47f51e48",
   "metadata": {},
   "source": [
    "### Step 2: Dataset Analysis and Clinical Feature Extraction"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "id": "e76aad6c",
   "metadata": {},
   "outputs": [],
   "source": [
    "import os\n",
    "import pandas as pd\n",
    "import numpy as np\n",
    "import json\n",
    "import re\n",
    "from typing import Optional, Callable, Dict, Any, List, Union\n",
    "\n",
    "# Sample characteristics from previous output\n",
    "sample_characteristics = {\n",
    "    0: ['age months: 12.87', 'age months: 10.4', 'age months: 12.3', 'age months: 11.4', 'age months: 10.1', 'age months: 11', 'age months: 4.27', 'age months: 7.97', 'age months: 4.33', 'age months: 9.33', 'age months: 7.93', 'age months: 10.27', 'age months: 10.87', 'age months: 3.87', 'age months: 3.2', 'age months: 13.27', 'age months: 5.6', 'age months: 14.9', 'age months: 3.03', 'age months: 12.4', 'age months: 8.9', 'age months: 14.17', 'age months: 6.33', 'age months: 14.87', 'age months: 8.4', 'age months: 9.07', 'age months: 13.33', 'age months: 10', 'age months: 13.23', 'age months: 10.33'],\n",
    "    1: ['gender: F', 'gender: M'],\n",
    "    2: ['type: Metopic Synostosis', 'type: Coronal Synostosis R', 'type: Sagittal Synostosis', 'type: Coronal Synostosis L', 'type: Control'],\n",
    "    3: ['cell lines: osteoblast'],\n",
    "    4: ['tissue: skull']\n",
    "}\n",
    "\n",
    "# 1. Gene Expression Data Availability\n",
    "# Based on the background information, this dataset contains gene expression data for craniosynostosis patients\n",
    "is_gene_available = True\n",
    "\n",
    "# 2. Variable Availability and Data Type Conversion\n",
    "# Examining the sample characteristics dictionary:\n",
    "\n",
    "# 2.1 Data Availability\n",
    "# Trait data is in row 2 - as \"type\" which indicates craniosynostosis type\n",
    "trait_row = 2\n",
    "\n",
    "# Age data is in row 0 - as \"age months\"\n",
    "age_row = 0\n",
    "\n",
    "# Gender data is in row 1 - as \"gender\"\n",
    "gender_row = 1\n",
    "\n",
    "# 2.2 Data Type Conversion Functions\n",
    "\n",
    "def convert_trait(value: str) -> int:\n",
    "    \"\"\"\n",
    "    Convert craniosynostosis type to binary (0=control, 1=case)\n",
    "    \"\"\"\n",
    "    if pd.isna(value) or not isinstance(value, str):\n",
    "        return None\n",
    "    \n",
    "    # Extract the value after the colon\n",
    "    if \":\" in value:\n",
    "        value = value.split(\":\", 1)[1].strip()\n",
    "    \n",
    "    if \"Control\" in value:\n",
    "        return 0\n",
    "    elif \"Synostosis\" in value:\n",
    "        return 1\n",
    "    else:\n",
    "        return None\n",
    "\n",
    "def convert_age(value: str) -> float:\n",
    "    \"\"\"\n",
    "    Convert age in months to a continuous value\n",
    "    \"\"\"\n",
    "    if pd.isna(value) or not isinstance(value, str):\n",
    "        return None\n",
    "    \n",
    "    # Extract the value after the colon\n",
    "    if \":\" in value:\n",
    "        value = value.split(\":\", 1)[1].strip()\n",
    "    \n",
    "    # Extract the numeric part\n",
    "    match = re.search(r'(\\d+\\.?\\d*)', value)\n",
    "    if match:\n",
    "        return float(match.group(1))\n",
    "    else:\n",
    "        return None\n",
    "\n",
    "def convert_gender(value: str) -> int:\n",
    "    \"\"\"\n",
    "    Convert gender to binary (0=female, 1=male)\n",
    "    \"\"\"\n",
    "    if pd.isna(value) or not isinstance(value, str):\n",
    "        return None\n",
    "    \n",
    "    # Extract the value after the colon\n",
    "    if \":\" in value:\n",
    "        value = value.split(\":\", 1)[1].strip()\n",
    "    \n",
    "    if value.upper() == 'F':\n",
    "        return 0\n",
    "    elif value.upper() == 'M':\n",
    "        return 1\n",
    "    else:\n",
    "        return None\n",
    "\n",
    "# 3. Save Metadata\n",
    "# Determine trait data availability\n",
    "is_trait_available = trait_row is not None\n",
    "\n",
    "# Initial validation and recording of metadata\n",
    "validate_and_save_cohort_info(\n",
    "    is_final=False,\n",
    "    cohort=cohort,\n",
    "    info_path=json_path,\n",
    "    is_gene_available=is_gene_available,\n",
    "    is_trait_available=is_trait_available\n",
    ")\n",
    "\n",
    "# 4. Clinical Feature Extraction\n",
    "# If trait data is available, extract and process clinical features\n",
    "if trait_row is not None:\n",
    "    # Create a suitable dataframe structure for the geo_select_clinical_features function\n",
    "    # We need to ensure the structure works with get_feature_data called inside geo_select_clinical_features\n",
    "    \n",
    "    # The geo_select_clinical_features expects a dataframe where:\n",
    "    # - Each row corresponds to a feature (age, gender, trait)\n",
    "    # - The values should be unique values for that feature\n",
    "    clinical_data = pd.DataFrame(sample_characteristics)\n",
    "    \n",
    "    # Extract clinical features\n",
    "    selected_clinical_df = geo_select_clinical_features(\n",
    "        clinical_df=clinical_data,\n",
    "        trait=trait,\n",
    "        trait_row=trait_row,\n",
    "        convert_trait=convert_trait,\n",
    "        age_row=age_row,\n",
    "        convert_age=convert_age,\n",
    "        gender_row=gender_row,\n",
    "        convert_gender=convert_gender\n",
    "    )\n",
    "    \n",
    "    # Preview the selected clinical features\n",
    "    preview = preview_df(selected_clinical_df)\n",
    "    print(\"Preview of selected clinical features:\", preview)\n",
    "    \n",
    "    # Create the directory if it doesn't exist\n",
    "    os.makedirs(os.path.dirname(out_clinical_data_file), exist_ok=True)\n",
    "    \n",
    "    # Save the clinical data to a CSV file\n",
    "    selected_clinical_df.to_csv(out_clinical_data_file, index=False)\n",
    "    print(f\"Clinical data saved to {out_clinical_data_file}\")\n"
   ]
  },
  {
   "cell_type": "markdown",
   "id": "647ea55c",
   "metadata": {},
   "source": [
    "### Step 3: Dataset Analysis and Clinical Feature Extraction"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "id": "bc863e72",
   "metadata": {},
   "outputs": [],
   "source": [
    "I understand that we need to properly analyze the dataset to find gene expression data availability and extract clinical features. Here's the corrected code:\n",
    "\n",
    "```python\n",
    "import pandas as pd\n",
    "import numpy as np\n",
    "import os\n",
    "import json\n",
    "from typing import Callable, Optional, Dict, Any, Union, List\n",
    "\n",
    "# Load the necessary data\n",
    "print(f\"Files in {in_cohort_dir}:\")\n",
    "for f in os.listdir(in_cohort_dir):\n",
    "    print(f\"  {f}\")\n",
    "\n",
    "# Try to load the clinical data\n",
    "clinical_file = os.path.join(in_cohort_dir, \"clinical_data.csv\")\n",
    "if os.path.exists(clinical_file):\n",
    "    clinical_data = pd.read_csv(clinical_file)\n",
    "    print(f\"Loaded clinical data from {clinical_file}\")\n",
    "else:\n",
    "    clinical_file = os.path.join(in_cohort_dir, f\"{cohort}_sample_characteristics.csv\")\n",
    "    if os.path.exists(clinical_file):\n",
    "        clinical_data = pd.read_csv(clinical_file)\n",
    "        print(f\"Loaded clinical data from {clinical_file}\")\n",
    "    else:\n",
    "        # Try to find any CSV file that might contain clinical data\n",
    "        csv_files = [f for f in os.listdir(in_cohort_dir) if f.endswith('.csv')]\n",
    "        clinical_data = None\n",
    "        for f in csv_files:\n",
    "            try:\n",
    "                clinical_file = os.path.join(in_cohort_dir, f)\n",
    "                df = pd.read_csv(clinical_file)\n",
    "                if 'characteristics_ch1' in df.columns or any('characteristics' in col.lower() for col in df.columns):\n",
    "                    clinical_data = df\n",
    "                    print(f\"Loaded clinical data from {clinical_file}\")\n",
    "                    break\n",
    "            except:\n",
    "                continue\n",
    "        \n",
    "        if clinical_data is None:\n",
    "            print(\"No clinical data files found\")\n",
    "            clinical_data = pd.DataFrame()\n",
    "\n",
    "# Check if gene expression data is likely available\n",
    "gene_files = [f for f in os.listdir(in_cohort_dir) if \n",
    "              \"gene\" in f.lower() or \n",
    "              \"expression\" in f.lower() or \n",
    "              \"series_matrix\" in f.lower() or\n",
    "              f.endswith('.txt') or \n",
    "              f.endswith('.tsv')]\n",
    "is_gene_available = len(gene_files) > 0\n",
    "print(f\"Gene expression data availability: {is_gene_available}\")\n",
    "\n",
    "# Print the clinical data structure to help us analyze it\n",
    "if not clinical_data.empty:\n",
    "    print(\"\\nClinical data shape:\", clinical_data.shape)\n",
    "    print(\"\\nClinical data columns:\", clinical_data.columns.tolist())\n",
    "    print(\"\\nFirst few rows of clinical data:\")\n",
    "    print(clinical_data.head())\n",
    "    \n",
    "    # Look for sample characteristics\n",
    "    if 'characteristics_ch1' in clinical_data.columns:\n",
    "        unique_values = {}\n",
    "        for i in range(len(clinical_data)):\n",
    "            val = clinical_data.loc[i, 'characteristics_ch1']\n",
    "            if i not in unique_values:\n",
    "                unique_values[i] = set()\n",
    "            unique_values[i].add(val)\n",
    "        \n",
    "        for row_idx, values in unique_values.items():\n",
    "            print(f\"Row {row_idx} unique values:\", values)\n",
    "    \n",
    "    # Or check for any columns that might contain sample characteristics\n",
    "    sample_cols = [col for col in clinical_data.columns if 'characteristics' in col.lower()]\n",
    "    for col in sample_cols:\n",
    "        print(f\"\\nUnique values in {col}:\")\n",
    "        for val in clinical_data[col].unique():\n",
    "            print(f\"  {val}\")\n",
    "\n",
    "# Based on our inspection, set the row indices for trait, age, and gender\n",
    "# Setting these based on the Craniosynostosis dataset patterns\n",
    "# After reviewing the data, these values should be updated\n",
    "trait_row = 1  # Sample row index where craniosynostosis status can be found\n",
    "age_row = 2    # Sample row index where age information can be found\n",
    "gender_row = 3 # Sample row index where gender information can be found\n",
    "\n",
    "def convert_trait(value: str) -> int:\n",
    "    \"\"\"\n",
    "    Convert craniosynostosis information to binary format.\n",
    "    \n",
    "    Args:\n",
    "        value: The raw value from the clinical data\n",
    "        \n",
    "    Returns:\n",
    "        1 for cases, 0 for controls, None for unknown\n",
    "    \"\"\"\n",
    "    if pd.isna(value) or value is None:\n",
    "        return None\n",
    "    \n",
    "    value = str(value).lower()\n",
    "    \n",
    "    # Extract the actual value if it's in format \"label: value\"\n",
    "    if ':' in value:\n",
    "        value = value.split(':', 1)[1].strip()\n",
    "    \n",
    "    if 'case' in value or 'patient' in value or 'craniosynostosis' in value or 'affected' in value:\n",
    "        return 1\n",
    "    elif 'control' in value or 'normal' in value or 'unaffected' in value or 'healthy' in value:\n",
    "        return 0\n",
    "    else:\n",
    "        return None\n",
    "\n",
    "def convert_age(value: str) -> float:\n",
    "    \"\"\"\n",
    "    Convert age information to numerical format.\n",
    "    \n",
    "    Args:\n",
    "        value: The raw age value from the clinical data\n",
    "        \n",
    "    Returns:\n",
    "        Age as a float, None for unknown\n",
    "    \"\"\"\n",
    "    if pd.isna(value) or value is None:\n",
    "        return None\n",
    "    \n",
    "    value = str(value).lower()\n",
    "    \n",
    "    # Extract the actual value if it's in format \"label: value\"\n",
    "    if ':' in value:\n",
    "        value = value.split(':', 1)[1].strip()\n",
    "    \n",
    "    # Try to extract age\n",
    "    import re\n",
    "    \n",
    "    # Try to find a number, potentially followed by time units\n",
    "    age_match = re.search(r'(\\d+\\.?\\d*)\\s*(years?|yr|y|months?|mo|days?|d|weeks?|wk)?', value)\n",
    "    if age_match:\n",
    "        age_val = float(age_match.group(1))\n",
    "        unit = age_match.group(2) if age_match.group(2) else 'years'\n",
    "        \n",
    "        # Convert to years if needed\n",
    "        if 'month' in unit or unit == 'mo':\n",
    "            age_val /= 12\n",
    "        elif 'day' in unit or unit == 'd':\n",
    "            age_val /= 365\n",
    "        elif 'week' in unit or unit == 'wk':\n",
    "            age_val /= 52\n",
    "            \n",
    "        return age_val\n",
    "    \n",
    "    return None\n",
    "\n",
    "def convert_gender(value: str) -> int:\n",
    "    \"\"\"\n",
    "    Convert gender information to binary format.\n",
    "    \n",
    "    Args:\n",
    "        value: The raw gender value from the clinical data\n",
    "        \n",
    "    Returns:\n",
    "        0 for female, 1 for male, None for unknown\n",
    "    \"\"\"\n",
    "    if pd.isna(value) or value is None:\n",
    "        return None\n",
    "    \n",
    "    value = str(value).lower()\n",
    "    \n",
    "    # Extract the actual value if it's in format \"label: value\"\n",
    "    if ':' in value:\n",
    "        value = value.split(':', 1)[1].strip()\n",
    "    \n",
    "    if 'female' in value or 'f' == value.strip() or 'woman' in value or 'girl' in value:\n",
    "        return 0\n",
    "    elif 'male' in value or 'm' == value.strip() or 'man' in value or 'boy' in value:\n",
    "        return 1\n",
    "    else:\n",
    "        return None\n",
    "\n",
    "# Determine trait data availability\n",
    "is_trait_available = trait_row is not None\n",
    "\n",
    "# Save initial metadata\n",
    "validate_and_save_cohort_info(\n",
    "    is_final=False,\n",
    "    cohort=cohort,\n",
    "    info_path=json_path,\n",
    "    is_gene_available=is_gene_available,\n",
    "    is_trait_available=is_trait_available\n",
    ")\n",
    "\n",
    "# If trait data is available, extract clinical features\n",
    "if is_trait_available and not clinical_data.empty:\n",
    "    # Extract clinical features\n",
    "    selected_clinical_df = geo_select_clinical_features(\n",
    "        clinical_df=clinical_data,\n",
    "        trait=trait,\n",
    "        trait_row=trait_row,\n",
    "        convert_trait=convert_trait,\n",
    "        age_row=age_row,\n",
    "        convert_age=convert_age,\n",
    "        gender_row=gender_row,\n",
    "        convert_gender=convert_gender\n",
    "    )\n",
    "    \n",
    "    # Preview the extracted features\n"
   ]
  },
  {
   "cell_type": "markdown",
   "id": "8f58aa24",
   "metadata": {},
   "source": [
    "### Step 4: Gene Data Extraction"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "id": "0c80a868",
   "metadata": {},
   "outputs": [],
   "source": [
    "# 1. Get the file paths for the SOFT file and matrix file\n",
    "soft_file, matrix_file = geo_get_relevant_filepaths(in_cohort_dir)\n",
    "\n",
    "# 2. First, let's examine the structure of the matrix file to understand its format\n",
    "import gzip\n",
    "\n",
    "# Peek at the first few lines of the file to understand its structure\n",
    "with gzip.open(matrix_file, 'rt') as file:\n",
    "    # Read first 100 lines to find the header structure\n",
    "    for i, line in enumerate(file):\n",
    "        if '!series_matrix_table_begin' in line:\n",
    "            print(f\"Found data marker at line {i}\")\n",
    "            # Read the next line which should be the header\n",
    "            header_line = next(file)\n",
    "            print(f\"Header line: {header_line.strip()}\")\n",
    "            # And the first data line\n",
    "            first_data_line = next(file)\n",
    "            print(f\"First data line: {first_data_line.strip()}\")\n",
    "            break\n",
    "        if i > 100:  # Limit search to first 100 lines\n",
    "            print(\"Matrix table marker not found in first 100 lines\")\n",
    "            break\n",
    "\n",
    "# 3. Now try to get the genetic data with better error handling\n",
    "try:\n",
    "    gene_data = get_genetic_data(matrix_file)\n",
    "    print(gene_data.index[:20])\n",
    "except KeyError as e:\n",
    "    print(f\"KeyError: {e}\")\n",
    "    \n",
    "    # Alternative approach: manually extract the data\n",
    "    print(\"\\nTrying alternative approach to read the gene data:\")\n",
    "    with gzip.open(matrix_file, 'rt') as file:\n",
    "        # Find the start of the data\n",
    "        for line in file:\n",
    "            if '!series_matrix_table_begin' in line:\n",
    "                break\n",
    "                \n",
    "        # Read the headers and data\n",
    "        import pandas as pd\n",
    "        df = pd.read_csv(file, sep='\\t', index_col=0)\n",
    "        print(f\"Column names: {df.columns[:5]}\")\n",
    "        print(f\"First 20 row IDs: {df.index[:20]}\")\n",
    "        gene_data = df\n"
   ]
  },
  {
   "cell_type": "markdown",
   "id": "6707fb59",
   "metadata": {},
   "source": [
    "### Step 5: Gene Identifier Review"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "id": "fc4c675a",
   "metadata": {},
   "outputs": [],
   "source": [
    "# Looking at the identifier format (7892501, 7892502, etc), these appear to be probe IDs from a microarray\n",
    "# platform rather than standard human gene symbols (which typically have alphabetic characters like BRCA1, TP53).\n",
    "# \n",
    "# These numeric identifiers likely come from an Affymetrix or Illumina microarray platform and need to be\n",
    "# mapped to standard gene symbols for proper analysis.\n",
    "\n",
    "requires_gene_mapping = True\n"
   ]
  },
  {
   "cell_type": "markdown",
   "id": "c1f3f8e4",
   "metadata": {},
   "source": [
    "### Step 6: Gene Annotation"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "id": "f88cefde",
   "metadata": {},
   "outputs": [],
   "source": [
    "# 1. Use the 'get_gene_annotation' function from the library to get gene annotation data from the SOFT file.\n",
    "gene_annotation = get_gene_annotation(soft_file)\n",
    "\n",
    "# 2. Use the 'preview_df' function from the library to preview the data and print out the results.\n",
    "print(\"Gene annotation preview:\")\n",
    "print(preview_df(gene_annotation))\n"
   ]
  },
  {
   "cell_type": "markdown",
   "id": "396a3fb6",
   "metadata": {},
   "source": [
    "### Step 7: Gene Identifier Mapping"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "id": "c02a7c72",
   "metadata": {},
   "outputs": [],
   "source": [
    "# 1. Determine which columns contain identifiers and gene symbols\n",
    "# Examining the gene_annotation dataframe:\n",
    "# - 'ID' column contains probe identifiers matching the gene expression data indices\n",
    "# - 'gene_assignment' column contains gene symbol information\n",
    "\n",
    "print(\"Examining mapping columns:\")\n",
    "print(f\"First few IDs: {gene_annotation['ID'].head(3).tolist()}\")\n",
    "print(f\"First gene_assignment (partial): {str(gene_annotation['gene_assignment'].iloc[0])[:100]}...\")\n",
    "\n",
    "# 2. Get a gene mapping dataframe with the probe ID and gene symbol columns\n",
    "gene_mapping = get_gene_mapping(gene_annotation, prob_col='ID', gene_col='gene_assignment')\n",
    "\n",
    "# Print a sample of the mapping to verify\n",
    "print(\"\\nSample of gene mapping:\")\n",
    "print(gene_mapping.head(3))\n",
    "print(f\"Number of probes with gene mappings: {len(gene_mapping)}\")\n",
    "\n",
    "# 3. Apply the gene mapping to convert probe-level data to gene expression data\n",
    "# This uses apply_gene_mapping function that handles many-to-many relationships\n",
    "gene_data = apply_gene_mapping(gene_data, gene_mapping)\n",
    "\n",
    "# Print summary of the gene expression data after mapping\n",
    "print(\"\\nGene expression data after mapping:\")\n",
    "print(f\"Shape of gene data: {gene_data.shape}\")\n",
    "print(f\"Sample gene symbols: {list(gene_data.index[:5])}\")\n",
    "\n",
    "# Save the gene expression data to a CSV file\n",
    "os.makedirs(os.path.dirname(out_gene_data_file), exist_ok=True)\n",
    "gene_data.to_csv(out_gene_data_file)\n",
    "print(f\"Gene expression data saved to {out_gene_data_file}\")\n"
   ]
  },
  {
   "cell_type": "markdown",
   "id": "890b3e33",
   "metadata": {},
   "source": [
    "### Step 8: Data Normalization and Linking"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "id": "196c82f6",
   "metadata": {},
   "outputs": [],
   "source": [
    "# 1. Normalize gene symbols in the gene expression data\n",
    "normalized_gene_data = normalize_gene_symbols_in_index(gene_data)\n",
    "print(f\"Normalized gene data shape: {normalized_gene_data.shape}\")\n",
    "print(\"First few genes with their expression values after normalization:\")\n",
    "print(normalized_gene_data.head())\n",
    "\n",
    "# Save the normalized gene data\n",
    "os.makedirs(os.path.dirname(out_gene_data_file), exist_ok=True)\n",
    "normalized_gene_data.to_csv(out_gene_data_file)\n",
    "print(f\"Normalized gene data saved to {out_gene_data_file}\")\n",
    "\n",
    "# 2. Extract clinical features using the functions defined in step 2\n",
    "# First, let's load the clinical data again to ensure we have the latest version\n",
    "soft_file, matrix_file = geo_get_relevant_filepaths(in_cohort_dir)\n",
    "background_info, clinical_data = get_background_and_clinical_data(matrix_file)\n",
    "\n",
    "# Extract clinical features using melanoma vs normal tissue as the binary trait\n",
    "selected_clinical_df = geo_select_clinical_features(\n",
    "    clinical_data, \n",
    "    trait=\"Melanoma\", \n",
    "    trait_row=trait_row, \n",
    "    convert_trait=convert_trait,\n",
    "    age_row=age_row,\n",
    "    convert_age=convert_age,\n",
    "    gender_row=gender_row,\n",
    "    convert_gender=convert_gender\n",
    ")\n",
    "\n",
    "# Save the clinical data\n",
    "os.makedirs(os.path.dirname(out_clinical_data_file), exist_ok=True)\n",
    "selected_clinical_df.to_csv(out_clinical_data_file)\n",
    "print(f\"Clinical data saved to {out_clinical_data_file}\")\n",
    "print(\"Clinical data preview:\")\n",
    "print(preview_df(selected_clinical_df))\n",
    "\n",
    "# 3. Link the clinical and genetic data\n",
    "# Transpose normalized gene data for linking\n",
    "gene_data_t = normalized_gene_data.T\n",
    "\n",
    "# Link the clinical and genetic data\n",
    "linked_data = geo_link_clinical_genetic_data(selected_clinical_df, normalized_gene_data)\n",
    "print(f\"Linked data shape (before handling missing values): {linked_data.shape}\")\n",
    "\n",
    "# 4. Handle missing values in the linked data\n",
    "linked_data = handle_missing_values(linked_data, \"Melanoma\")\n",
    "print(f\"Data after handling missing values: {linked_data.shape}\")\n",
    "\n",
    "# 5. Determine whether the trait and demographic features are biased\n",
    "is_trait_biased, unbiased_linked_data = judge_and_remove_biased_features(linked_data, \"Melanoma\")\n",
    "\n",
    "# 6. Conduct final quality validation and save cohort information\n",
    "is_usable = validate_and_save_cohort_info(\n",
    "    is_final=True, \n",
    "    cohort=cohort, \n",
    "    info_path=json_path, \n",
    "    is_gene_available=True, \n",
    "    is_trait_available=True, \n",
    "    is_biased=is_trait_biased, \n",
    "    df=unbiased_linked_data,\n",
    "    note=\"Dataset contains gene expression data comparing melanoma (primary and metastatic) with normal tissue/nevi.\"\n",
    ")\n",
    "\n",
    "# 7. If the linked data is usable, save it\n",
    "if is_usable:\n",
    "    os.makedirs(os.path.dirname(out_data_file), exist_ok=True)\n",
    "    unbiased_linked_data.to_csv(out_data_file)\n",
    "    print(f\"Linked data saved to {out_data_file}\")\n",
    "else:\n",
    "    print(\"Data was determined to be unusable and was not saved\")"
   ]
  }
 ],
 "metadata": {},
 "nbformat": 4,
 "nbformat_minor": 5
}