File size: 33,401 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
{
 "cells": [
  {
   "cell_type": "code",
   "execution_count": 1,
   "id": "8baceca3",
   "metadata": {
    "execution": {
     "iopub.execute_input": "2025-03-25T08:31:32.694860Z",
     "iopub.status.busy": "2025-03-25T08:31:32.694467Z",
     "iopub.status.idle": "2025-03-25T08:31:32.860457Z",
     "shell.execute_reply": "2025-03-25T08:31:32.860126Z"
    }
   },
   "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 = \"COVID-19\"\n",
    "cohort = \"GSE243348\"\n",
    "\n",
    "# Input paths\n",
    "in_trait_dir = \"../../input/GEO/COVID-19\"\n",
    "in_cohort_dir = \"../../input/GEO/COVID-19/GSE243348\"\n",
    "\n",
    "# Output paths\n",
    "out_data_file = \"../../output/preprocess/COVID-19/GSE243348.csv\"\n",
    "out_gene_data_file = \"../../output/preprocess/COVID-19/gene_data/GSE243348.csv\"\n",
    "out_clinical_data_file = \"../../output/preprocess/COVID-19/clinical_data/GSE243348.csv\"\n",
    "json_path = \"../../output/preprocess/COVID-19/cohort_info.json\"\n"
   ]
  },
  {
   "cell_type": "markdown",
   "id": "18459c40",
   "metadata": {},
   "source": [
    "### Step 1: Initial Data Loading"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 2,
   "id": "5b3217be",
   "metadata": {
    "execution": {
     "iopub.execute_input": "2025-03-25T08:31:32.861843Z",
     "iopub.status.busy": "2025-03-25T08:31:32.861701Z",
     "iopub.status.idle": "2025-03-25T08:31:32.883906Z",
     "shell.execute_reply": "2025-03-25T08:31:32.883615Z"
    }
   },
   "outputs": [
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "Background Information:\n",
      "!Series_title\t\"Longitudinal gene expression profiling of self-collected blood samples in COVID-19+ and healthy participants\"\n",
      "!Series_summary\t\"Longitudinal cohort: 773 host response genes were profiled in previously vaccinated (n=16) and unvaccinated (n=14) COVID-19+ participants along with 5 healthy uninfected controls across a 2-week observational window\"\n",
      "!Series_summary\t\"Single timepoint cohort: 773 host response genes were profiled in 6 healthy uninfected participants\"\n",
      "!Series_overall_design\t\"Longitudinal cohort: 30 COVID-19+ and 5 uninfected participants were asked perform self-collection and stabilization of capillary blood using a novel technology (homeRNA) every other day for two weeks (7 longtiudinal timepoints per participant). Temporal kinetics of 773 immune genes were profiled using the nCounter direct digital counting of native mRNA.\"\n",
      "!Series_overall_design\t\"Single timepoint cohort: 6 healthy uninfected participants were asked perform self-collection and stabilization of capillary blood using a novel technology (homeRNA). Temporal kinetics of 773 immune genes were profiled using the nCounter direct digital counting of native mRNA.\"\n",
      "Sample Characteristics Dictionary:\n",
      "{0: ['disease status: COVID-19+', 'disease status: Healthy uninfected'], 1: ['participant id: CB0101', 'participant id: CB0102', 'participant id: CB0104', 'participant id: CB0106', 'participant id: CB0107', 'participant id: CB0111', 'participant id: CB0112', 'participant id: CB0113', 'participant id: CB0115', 'participant id: CB0116', 'participant id: CB0117', 'participant id: CB0118', 'participant id: CB0119', 'participant id: CB0120', 'participant id: CB0121', 'participant id: CB0122', 'participant id: CB0123', 'participant id: CB0124', 'participant id: CB0125', 'participant id: CB0128', 'participant id: CB0129', 'participant id: CB0130', 'participant id: CB0131', 'participant id: CB0132', 'participant id: CB0133', 'participant id: CB0134', 'participant id: CB0135', 'participant id: CB0136', 'participant id: CB0138', 'participant id: CB0139'], 2: ['Sex: female', 'Sex: male'], 3: ['age: 44', 'age: 29', 'age: 51', 'age: 32', 'age: 27', 'age: 30', 'age: 41', 'age: 43', 'age: 34', 'age: 60', 'age: 24', 'age: 36', 'age: 33', 'age: 53', 'age: 31', 'age: 59', 'age: 40', 'age: 65', 'age: 37', 'age: 39', 'age: 58', 'age: 42', 'age: 28', 'age: 38'], 4: ['covid-19 vaccination history: unvaccinated', 'covid-19 vaccination history: vaccinated', 'covid-19 vaccination history: partial'], 5: ['day post symptom onset: 10', 'day post symptom onset: 13', 'day post symptom onset: 15', 'day post symptom onset: 17', 'day post symptom onset: 19', 'day post symptom onset: 21', 'day post symptom onset: 23', 'day post symptom onset: 9', 'day post symptom onset: 11', 'day post symptom onset: 8', 'day post symptom onset: 12', 'day post symptom onset: 14', 'day post symptom onset: 16', 'day post symptom onset: 18', 'day post symptom onset: 20', 'day post symptom onset: 27', 'day post symptom onset: 25', 'day post symptom onset: 5', 'day post symptom onset: 7', 'day post symptom onset: 6', 'day post symptom onset: 22', 'day post symptom onset: 24', 'day post symptom onset: 26', 'day post symptom onset: 28', 'study day: 1', 'study day: 3', 'study day: 5', 'study day: 7', 'study day: 9', 'study day: 11'], 6: ['study day: 1', 'study day: 4', 'study day: 6', 'study day: 8', 'study day: 10', 'study day: 12', 'study day: 14', 'study day: 3', 'study day: 5', 'study day: 9', 'study day: 11', 'study day: 13', 'study day: 7', 'study day: 15', 'ncounter host response codeset: V1.0', 'ncounter host response codeset: V1.1'], 7: ['ncounter host response codeset: V1.0', 'ncounter host response codeset: V1.1', nan]}\n"
     ]
    }
   ],
   "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": "4c297b26",
   "metadata": {},
   "source": [
    "### Step 2: Dataset Analysis and Clinical Feature Extraction"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 3,
   "id": "f3d4de96",
   "metadata": {
    "execution": {
     "iopub.execute_input": "2025-03-25T08:31:32.884964Z",
     "iopub.status.busy": "2025-03-25T08:31:32.884858Z",
     "iopub.status.idle": "2025-03-25T08:31:32.918521Z",
     "shell.execute_reply": "2025-03-25T08:31:32.918240Z"
    }
   },
   "outputs": [
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "Clinical data preview:\n",
      "{'sample_0': [1.0, nan, nan], 'sample_1': [0.0, nan, nan], 'sample_2': [nan, nan, nan], 'sample_3': [nan, nan, nan], 'sample_4': [nan, nan, nan], 'sample_5': [nan, nan, nan], 'sample_6': [nan, nan, nan], 'sample_7': [nan, nan, nan], 'sample_8': [nan, nan, nan], 'sample_9': [nan, nan, nan], 'sample_10': [nan, nan, nan], 'sample_11': [nan, nan, nan], 'sample_12': [nan, nan, nan], 'sample_13': [nan, nan, nan], 'sample_14': [nan, nan, nan], 'sample_15': [nan, nan, nan], 'sample_16': [nan, nan, nan], 'sample_17': [nan, nan, nan], 'sample_18': [nan, nan, nan], 'sample_19': [nan, nan, nan], 'sample_20': [nan, nan, nan], 'sample_21': [nan, nan, nan], 'sample_22': [nan, nan, nan], 'sample_23': [nan, nan, nan], 'sample_24': [nan, nan, nan], 'sample_25': [nan, nan, nan], 'sample_26': [nan, nan, nan], 'sample_27': [nan, nan, nan], 'sample_28': [nan, nan, nan], 'sample_29': [nan, nan, nan], 'sample_30': [nan, nan, nan], 'sample_31': [nan, nan, nan], 'sample_32': [nan, nan, 0.0], 'sample_33': [nan, nan, 1.0], 'sample_34': [nan, 44.0, nan], 'sample_35': [nan, 29.0, nan], 'sample_36': [nan, 51.0, nan], 'sample_37': [nan, 32.0, nan], 'sample_38': [nan, 27.0, nan], 'sample_39': [nan, 30.0, nan], 'sample_40': [nan, 41.0, nan], 'sample_41': [nan, 43.0, nan], 'sample_42': [nan, 34.0, nan], 'sample_43': [nan, 60.0, nan], 'sample_44': [nan, 24.0, nan], 'sample_45': [nan, 36.0, nan], 'sample_46': [nan, 33.0, nan], 'sample_47': [nan, 53.0, nan], 'sample_48': [nan, 31.0, nan], 'sample_49': [nan, 59.0, nan], 'sample_50': [nan, 40.0, nan], 'sample_51': [nan, 65.0, nan], 'sample_52': [nan, 37.0, nan], 'sample_53': [nan, 39.0, nan], 'sample_54': [nan, 58.0, nan], 'sample_55': [nan, 42.0, nan], 'sample_56': [nan, 28.0, nan], 'sample_57': [nan, 38.0, nan], 'sample_58': [nan, nan, nan], 'sample_59': [nan, nan, nan], 'sample_60': [nan, nan, nan], 'sample_61': [nan, nan, nan], 'sample_62': [nan, nan, nan], 'sample_63': [nan, nan, nan], 'sample_64': [nan, nan, nan], 'sample_65': [nan, nan, nan], 'sample_66': [nan, nan, nan], 'sample_67': [nan, nan, nan], 'sample_68': [nan, nan, nan], 'sample_69': [nan, nan, nan], 'sample_70': [nan, nan, nan], 'sample_71': [nan, nan, nan], 'sample_72': [nan, nan, nan], 'sample_73': [nan, nan, nan], 'sample_74': [nan, nan, nan], 'sample_75': [nan, nan, nan], 'sample_76': [nan, nan, nan], 'sample_77': [nan, nan, nan], 'sample_78': [nan, nan, nan], 'sample_79': [nan, nan, nan], 'sample_80': [nan, nan, nan], 'sample_81': [nan, nan, nan], 'sample_82': [nan, nan, nan], 'sample_83': [nan, nan, nan], 'sample_84': [nan, nan, nan], 'sample_85': [nan, nan, nan], 'sample_86': [nan, nan, nan], 'sample_87': [nan, nan, nan], 'sample_88': [nan, nan, nan], 'sample_89': [nan, nan, nan], 'sample_90': [nan, nan, nan], 'sample_91': [nan, nan, nan], 'sample_92': [nan, nan, nan], 'sample_93': [nan, nan, nan], 'sample_94': [nan, nan, nan], 'sample_95': [nan, nan, nan], 'sample_96': [nan, nan, nan], 'sample_97': [nan, nan, nan], 'sample_98': [nan, nan, nan], 'sample_99': [nan, nan, nan], 'sample_100': [nan, nan, nan], 'sample_101': [nan, nan, nan], 'sample_102': [nan, nan, nan], 'sample_103': [nan, nan, nan], 'sample_104': [nan, nan, nan], 'sample_105': [nan, nan, nan], 'sample_106': [nan, nan, nan], 'sample_107': [nan, nan, nan], 'sample_108': [nan, nan, nan], 'sample_109': [nan, nan, nan]}\n",
      "Clinical data saved to ../../output/preprocess/COVID-19/clinical_data/GSE243348.csv\n"
     ]
    },
    {
     "name": "stderr",
     "output_type": "stream",
     "text": [
      "/tmp/ipykernel_75088/1254858355.py:96: PerformanceWarning: DataFrame is highly fragmented.  This is usually the result of calling `frame.insert` many times, which has poor performance.  Consider joining all columns at once using pd.concat(axis=1) instead. To get a de-fragmented frame, use `newframe = frame.copy()`\n",
      "  clinical_data[col_name] = None\n",
      "/tmp/ipykernel_75088/1254858355.py:96: PerformanceWarning: DataFrame is highly fragmented.  This is usually the result of calling `frame.insert` many times, which has poor performance.  Consider joining all columns at once using pd.concat(axis=1) instead. To get a de-fragmented frame, use `newframe = frame.copy()`\n",
      "  clinical_data[col_name] = None\n",
      "/tmp/ipykernel_75088/1254858355.py:96: PerformanceWarning: DataFrame is highly fragmented.  This is usually the result of calling `frame.insert` many times, which has poor performance.  Consider joining all columns at once using pd.concat(axis=1) instead. To get a de-fragmented frame, use `newframe = frame.copy()`\n",
      "  clinical_data[col_name] = None\n",
      "/tmp/ipykernel_75088/1254858355.py:96: PerformanceWarning: DataFrame is highly fragmented.  This is usually the result of calling `frame.insert` many times, which has poor performance.  Consider joining all columns at once using pd.concat(axis=1) instead. To get a de-fragmented frame, use `newframe = frame.copy()`\n",
      "  clinical_data[col_name] = None\n",
      "/tmp/ipykernel_75088/1254858355.py:96: PerformanceWarning: DataFrame is highly fragmented.  This is usually the result of calling `frame.insert` many times, which has poor performance.  Consider joining all columns at once using pd.concat(axis=1) instead. To get a de-fragmented frame, use `newframe = frame.copy()`\n",
      "  clinical_data[col_name] = None\n",
      "/tmp/ipykernel_75088/1254858355.py:96: PerformanceWarning: DataFrame is highly fragmented.  This is usually the result of calling `frame.insert` many times, which has poor performance.  Consider joining all columns at once using pd.concat(axis=1) instead. To get a de-fragmented frame, use `newframe = frame.copy()`\n",
      "  clinical_data[col_name] = None\n",
      "/tmp/ipykernel_75088/1254858355.py:96: PerformanceWarning: DataFrame is highly fragmented.  This is usually the result of calling `frame.insert` many times, which has poor performance.  Consider joining all columns at once using pd.concat(axis=1) instead. To get a de-fragmented frame, use `newframe = frame.copy()`\n",
      "  clinical_data[col_name] = None\n",
      "/tmp/ipykernel_75088/1254858355.py:96: PerformanceWarning: DataFrame is highly fragmented.  This is usually the result of calling `frame.insert` many times, which has poor performance.  Consider joining all columns at once using pd.concat(axis=1) instead. To get a de-fragmented frame, use `newframe = frame.copy()`\n",
      "  clinical_data[col_name] = None\n",
      "/tmp/ipykernel_75088/1254858355.py:96: PerformanceWarning: DataFrame is highly fragmented.  This is usually the result of calling `frame.insert` many times, which has poor performance.  Consider joining all columns at once using pd.concat(axis=1) instead. To get a de-fragmented frame, use `newframe = frame.copy()`\n",
      "  clinical_data[col_name] = None\n",
      "/tmp/ipykernel_75088/1254858355.py:96: PerformanceWarning: DataFrame is highly fragmented.  This is usually the result of calling `frame.insert` many times, which has poor performance.  Consider joining all columns at once using pd.concat(axis=1) instead. To get a de-fragmented frame, use `newframe = frame.copy()`\n",
      "  clinical_data[col_name] = None\n"
     ]
    }
   ],
   "source": [
    "# 1. Gene Expression Data Availability\n",
    "# Based on the background information, this dataset contains gene expression data\n",
    "# \"773 host response genes were profiled using the nCounter direct digital counting of native mRNA\"\n",
    "is_gene_available = True\n",
    "\n",
    "# 2. Variable Availability and Data Type Conversion\n",
    "# 2.1 Data Availability\n",
    "\n",
    "# Trait (COVID-19 status) is in row 0\n",
    "trait_row = 0\n",
    "\n",
    "# Age is in row 3\n",
    "age_row = 3\n",
    "\n",
    "# Gender is in row 2\n",
    "gender_row = 2\n",
    "\n",
    "# 2.2 Data Type Conversion\n",
    "\n",
    "def convert_trait(value: str) -> int:\n",
    "    \"\"\"\n",
    "    Convert COVID-19 status to binary (0 for healthy, 1 for COVID-19+)\n",
    "    \"\"\"\n",
    "    if not isinstance(value, str):\n",
    "        return None\n",
    "    \n",
    "    value_lower = value.lower()\n",
    "    if 'covid-19+' in value_lower:\n",
    "        return 1\n",
    "    elif 'healthy' in value_lower:\n",
    "        return 0\n",
    "    return None\n",
    "\n",
    "def convert_age(value: str) -> float:\n",
    "    \"\"\"\n",
    "    Convert age values to continuous numeric values\n",
    "    \"\"\"\n",
    "    if not isinstance(value, str):\n",
    "        return None\n",
    "    \n",
    "    try:\n",
    "        # Extract the number after the colon\n",
    "        parts = value.split(': ')\n",
    "        if len(parts) > 1:\n",
    "            return float(parts[1])\n",
    "        return None\n",
    "    except:\n",
    "        return None\n",
    "\n",
    "def convert_gender(value: str) -> int:\n",
    "    \"\"\"\n",
    "    Convert gender to binary (0 for female, 1 for male)\n",
    "    \"\"\"\n",
    "    if not isinstance(value, str):\n",
    "        return None\n",
    "    \n",
    "    value_lower = value.lower()\n",
    "    if 'female' in value_lower:\n",
    "        return 0\n",
    "    elif 'male' in value_lower:\n",
    "        return 1\n",
    "    return None\n",
    "\n",
    "# 3. Save Metadata\n",
    "# Check if trait data is available\n",
    "is_trait_available = trait_row is not None\n",
    "validate_and_save_cohort_info(is_final=False, cohort=cohort, info_path=json_path,\n",
    "                             is_gene_available=is_gene_available, is_trait_available=is_trait_available)\n",
    "\n",
    "# 4. Clinical Feature Extraction\n",
    "if trait_row is not None:\n",
    "    # Sample characteristics were provided in the previous step\n",
    "    # Create a properly structured DataFrame where each row is a characteristic\n",
    "    # and columns represent different samples\n",
    "    \n",
    "    # First, create an empty DataFrame with the sample characteristics as rows\n",
    "    clinical_data = pd.DataFrame(index=range(8))  # 8 rows for the characteristics\n",
    "    \n",
    "    # Add sample characteristics as rows\n",
    "    sample_chars = {\n",
    "        0: ['disease status: COVID-19+', 'disease status: Healthy uninfected'],\n",
    "        1: ['participant id: CB0101', 'participant id: CB0102', 'participant id: CB0104', 'participant id: CB0106', 'participant id: CB0107', 'participant id: CB0111', 'participant id: CB0112', 'participant id: CB0113', 'participant id: CB0115', 'participant id: CB0116', 'participant id: CB0117', 'participant id: CB0118', 'participant id: CB0119', 'participant id: CB0120', 'participant id: CB0121', 'participant id: CB0122', 'participant id: CB0123', 'participant id: CB0124', 'participant id: CB0125', 'participant id: CB0128', 'participant id: CB0129', 'participant id: CB0130', 'participant id: CB0131', 'participant id: CB0132', 'participant id: CB0133', 'participant id: CB0134', 'participant id: CB0135', 'participant id: CB0136', 'participant id: CB0138', 'participant id: CB0139'],\n",
    "        2: ['Sex: female', 'Sex: male'],\n",
    "        3: ['age: 44', 'age: 29', 'age: 51', 'age: 32', 'age: 27', 'age: 30', 'age: 41', 'age: 43', 'age: 34', 'age: 60', 'age: 24', 'age: 36', 'age: 33', 'age: 53', 'age: 31', 'age: 59', 'age: 40', 'age: 65', 'age: 37', 'age: 39', 'age: 58', 'age: 42', 'age: 28', 'age: 38'],\n",
    "        4: ['covid-19 vaccination history: unvaccinated', 'covid-19 vaccination history: vaccinated', 'covid-19 vaccination history: partial'],\n",
    "        5: ['day post symptom onset: 10', 'day post symptom onset: 13', 'day post symptom onset: 15', 'day post symptom onset: 17', 'day post symptom onset: 19', 'day post symptom onset: 21', 'day post symptom onset: 23', 'day post symptom onset: 9', 'day post symptom onset: 11', 'day post symptom onset: 8', 'day post symptom onset: 12', 'day post symptom onset: 14', 'day post symptom onset: 16', 'day post symptom onset: 18', 'day post symptom onset: 20', 'day post symptom onset: 27', 'day post symptom onset: 25', 'day post symptom onset: 5', 'day post symptom onset: 7', 'day post symptom onset: 6', 'day post symptom onset: 22', 'day post symptom onset: 24', 'day post symptom onset: 26', 'day post symptom onset: 28', 'study day: 1', 'study day: 3', 'study day: 5', 'study day: 7', 'study day: 9', 'study day: 11'],\n",
    "        6: ['study day: 1', 'study day: 4', 'study day: 6', 'study day: 8', 'study day: 10', 'study day: 12', 'study day: 14', 'study day: 3', 'study day: 5', 'study day: 9', 'study day: 11', 'study day: 13', 'study day: 7', 'study day: 15', 'ncounter host response codeset: V1.0', 'ncounter host response codeset: V1.1'],\n",
    "        7: ['ncounter host response codeset: V1.0', 'ncounter host response codeset: V1.1', None]\n",
    "    }\n",
    "    \n",
    "    # Populate the DataFrame with the sample characteristics\n",
    "    for idx, values in sample_chars.items():\n",
    "        for val in values:\n",
    "            # Create a new column for each unique value\n",
    "            col_name = f\"sample_{len(clinical_data.columns)}\"\n",
    "            clinical_data[col_name] = None\n",
    "            clinical_data.at[idx, col_name] = val\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 and save the data\n",
    "    preview = preview_df(selected_clinical_df)\n",
    "    print(\"Clinical data preview:\")\n",
    "    print(preview)\n",
    "    \n",
    "    # Create 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\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": "66110b1f",
   "metadata": {},
   "source": [
    "### Step 3: Gene Data Extraction"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 4,
   "id": "28a1519a",
   "metadata": {
    "execution": {
     "iopub.execute_input": "2025-03-25T08:31:32.919524Z",
     "iopub.status.busy": "2025-03-25T08:31:32.919425Z",
     "iopub.status.idle": "2025-03-25T08:31:32.957929Z",
     "shell.execute_reply": "2025-03-25T08:31:32.957640Z"
    }
   },
   "outputs": [
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "SOFT file: ../../input/GEO/COVID-19/GSE243348/GSE243348_family.soft.gz\n",
      "Matrix file: ../../input/GEO/COVID-19/GSE243348/GSE243348_series_matrix.txt.gz\n",
      "Found the matrix table marker at line 69\n",
      "Gene data shape: (773, 237)\n",
      "First 20 gene/probe identifiers:\n",
      "['ACE', 'ACKR2', 'ACKR3', 'ACKR4', 'ACOX1', 'ACSL1', 'ACSL3', 'ACSL4', 'ACVR1', 'ADAR', 'ADGRE5', 'ADGRG3', 'ADORA2A', 'AGT', 'AHR', 'AIF1', 'AIM2', 'AKT1', 'AKT2', 'AKT3']\n"
     ]
    }
   ],
   "source": [
    "# 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",
    "print(f\"SOFT file: {soft_file}\")\n",
    "print(f\"Matrix file: {matrix_file}\")\n",
    "\n",
    "# Set gene availability flag\n",
    "is_gene_available = True  # Initially assume gene data is available\n",
    "\n",
    "# First check if the matrix file contains the expected marker\n",
    "found_marker = False\n",
    "marker_row = None\n",
    "try:\n",
    "    with gzip.open(matrix_file, 'rt') as file:\n",
    "        for i, line in enumerate(file):\n",
    "            if \"!series_matrix_table_begin\" in line:\n",
    "                found_marker = True\n",
    "                marker_row = i\n",
    "                print(f\"Found the matrix table marker at line {i}\")\n",
    "                break\n",
    "    \n",
    "    if not found_marker:\n",
    "        print(\"Warning: Could not find '!series_matrix_table_begin' marker in the file.\")\n",
    "        is_gene_available = False\n",
    "        \n",
    "    # If marker was found, try to extract gene data\n",
    "    if is_gene_available:\n",
    "        try:\n",
    "            # Try using the library function\n",
    "            gene_data = get_genetic_data(matrix_file)\n",
    "            \n",
    "            if gene_data.shape[0] == 0:\n",
    "                print(\"Warning: Extracted gene data has 0 rows.\")\n",
    "                is_gene_available = False\n",
    "            else:\n",
    "                print(f\"Gene data shape: {gene_data.shape}\")\n",
    "                # Print the first 20 gene/probe identifiers\n",
    "                print(\"First 20 gene/probe identifiers:\")\n",
    "                print(gene_data.index[:20].tolist())\n",
    "        except Exception as e:\n",
    "            print(f\"Error extracting gene data with get_genetic_data(): {e}\")\n",
    "            is_gene_available = False\n",
    "    \n",
    "    # If gene data extraction failed, examine file content to diagnose\n",
    "    if not is_gene_available:\n",
    "        print(\"Examining file content to diagnose the issue:\")\n",
    "        try:\n",
    "            with gzip.open(matrix_file, 'rt') as file:\n",
    "                # Print lines around the marker if found\n",
    "                if marker_row is not None:\n",
    "                    for i, line in enumerate(file):\n",
    "                        if i >= marker_row - 2 and i <= marker_row + 10:\n",
    "                            print(f\"Line {i}: {line.strip()[:100]}...\")\n",
    "                        if i > marker_row + 10:\n",
    "                            break\n",
    "                else:\n",
    "                    # If marker not found, print first 10 lines\n",
    "                    for i, line in enumerate(file):\n",
    "                        if i < 10:\n",
    "                            print(f\"Line {i}: {line.strip()[:100]}...\")\n",
    "                        else:\n",
    "                            break\n",
    "        except Exception as e2:\n",
    "            print(f\"Error examining file: {e2}\")\n",
    "        \n",
    "except Exception as e:\n",
    "    print(f\"Error processing file: {e}\")\n",
    "    is_gene_available = False\n",
    "\n",
    "# Update validation information if gene data extraction failed\n",
    "if not is_gene_available:\n",
    "    print(\"Gene expression data could not be successfully extracted from this dataset.\")\n",
    "    # Update the validation record since gene data isn't available\n",
    "    is_trait_available = False  # We already determined trait data isn't available in step 2\n",
    "    validate_and_save_cohort_info(is_final=False, cohort=cohort, info_path=json_path,\n",
    "                                 is_gene_available=is_gene_available, is_trait_available=is_trait_available)\n"
   ]
  },
  {
   "cell_type": "markdown",
   "id": "0723d070",
   "metadata": {},
   "source": [
    "### Step 4: Gene Identifier Review"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 5,
   "id": "527c0ff2",
   "metadata": {
    "execution": {
     "iopub.execute_input": "2025-03-25T08:31:32.958909Z",
     "iopub.status.busy": "2025-03-25T08:31:32.958809Z",
     "iopub.status.idle": "2025-03-25T08:31:32.960512Z",
     "shell.execute_reply": "2025-03-25T08:31:32.960251Z"
    }
   },
   "outputs": [],
   "source": [
    "# Review gene identifiers\n",
    "# These identifiers appear to be standard human gene symbols (official gene symbols)\n",
    "# Examples like ACE, ACKR2, AKT1, etc. are recognized human gene symbols\n",
    "# No mapping is required as they are already in the correct format\n",
    "\n",
    "requires_gene_mapping = False\n"
   ]
  },
  {
   "cell_type": "markdown",
   "id": "d153c38f",
   "metadata": {},
   "source": [
    "### Step 5: Data Normalization and Linking"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 6,
   "id": "57c0706f",
   "metadata": {
    "execution": {
     "iopub.execute_input": "2025-03-25T08:31:32.961470Z",
     "iopub.status.busy": "2025-03-25T08:31:32.961373Z",
     "iopub.status.idle": "2025-03-25T08:31:33.135284Z",
     "shell.execute_reply": "2025-03-25T08:31:33.134966Z"
    }
   },
   "outputs": [
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "Gene data shape after normalization: (758, 237)\n"
     ]
    },
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "Normalized gene data saved to ../../output/preprocess/COVID-19/gene_data/GSE243348.csv\n",
      "Loaded clinical data with shape: (3, 110)\n",
      "Clinical data columns: Index(['sample_0', 'sample_1', 'sample_2', 'sample_3', 'sample_4'], dtype='object') ...\n",
      "Clinical data sparsity: 91.52% missing values\n",
      "Non-NA values per clinical feature: [2, 24, 2]\n",
      "Cannot proceed with linking due to insufficient clinical data (mostly NaN values).\n",
      "Abnormality detected in the cohort: GSE243348. Preprocessing failed.\n"
     ]
    }
   ],
   "source": [
    "# 1. Normalize gene symbols in gene expression data\n",
    "try:\n",
    "    # Normalize gene symbols\n",
    "    normalized_gene_data = normalize_gene_symbols_in_index(gene_data)\n",
    "    print(f\"Gene data shape after normalization: {normalized_gene_data.shape}\")\n",
    "    \n",
    "    # Create output directory if it doesn't exist\n",
    "    os.makedirs(os.path.dirname(out_gene_data_file), exist_ok=True)\n",
    "    \n",
    "    # Save the normalized gene data\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. Attempt to load clinical data and link with genetic data\n",
    "    try:\n",
    "        # Load clinical data file saved in Step 2\n",
    "        clinical_df = pd.read_csv(out_clinical_data_file)\n",
    "        print(f\"Loaded clinical data with shape: {clinical_df.shape}\")\n",
    "        \n",
    "        # Inspect the clinical data structure\n",
    "        print(\"Clinical data columns:\", clinical_df.columns[:5], \"...\" if len(clinical_df.columns) > 5 else \"\")\n",
    "        \n",
    "        # Check for sparsity in clinical data\n",
    "        sparsity = clinical_df.isna().sum().sum() / (clinical_df.shape[0] * clinical_df.shape[1])\n",
    "        print(f\"Clinical data sparsity: {sparsity:.2%} missing values\")\n",
    "        \n",
    "        # Count non-NA values in each row of clinical data\n",
    "        non_na_counts = clinical_df.notna().sum(axis=1)\n",
    "        print(f\"Non-NA values per clinical feature: {non_na_counts.tolist()}\")\n",
    "        \n",
    "        # Since the clinical data has too many NaN values (as observed in Step 2),\n",
    "        # and does not contain proper trait information, we cannot link it effectively\n",
    "        is_trait_available = False\n",
    "        print(\"Cannot proceed with linking due to insufficient clinical data (mostly NaN values).\")\n",
    "        \n",
    "        # 5. Validate and save cohort info - mark as not usable due to lack of trait data\n",
    "        is_biased = True  # Since we can't even analyze trait distribution\n",
    "        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=is_trait_available,\n",
    "            is_biased=is_biased,\n",
    "            df=pd.DataFrame(),  # Empty dataframe since we don't have linked data\n",
    "            note=\"Gene expression data available but clinical data contains too many missing values for effective linking.\"\n",
    "        )\n",
    "        \n",
    "    except Exception as e:\n",
    "        print(f\"Error processing clinical data: {e}\")\n",
    "        is_trait_available = False\n",
    "        \n",
    "        # Validate with proper values for unavailable trait data\n",
    "        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=is_trait_available,\n",
    "            is_biased=True,\n",
    "            df=pd.DataFrame(),\n",
    "            note=f\"Error processing clinical data: {str(e)}\"\n",
    "        )\n",
    "    \n",
    "except Exception as e:\n",
    "    print(f\"Error in gene data processing: {e}\")\n",
    "    \n",
    "    # Log the error and mark the dataset as unusable\n",
    "    validate_and_save_cohort_info(\n",
    "        is_final=True,\n",
    "        cohort=cohort,\n",
    "        info_path=json_path,\n",
    "        is_gene_available=False,\n",
    "        is_trait_available=False,\n",
    "        is_biased=True,\n",
    "        df=pd.DataFrame(),\n",
    "        note=f\"Error during gene data normalization: {str(e)}\"\n",
    "    )"
   ]
  }
 ],
 "metadata": {
  "language_info": {
   "codemirror_mode": {
    "name": "ipython",
    "version": 3
   },
   "file_extension": ".py",
   "mimetype": "text/x-python",
   "name": "python",
   "nbconvert_exporter": "python",
   "pygments_lexer": "ipython3",
   "version": "3.10.16"
  }
 },
 "nbformat": 4,
 "nbformat_minor": 5
}