File size: 29,594 Bytes
92d2f89
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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
{
 "cells": [
  {
   "cell_type": "code",
   "execution_count": 1,
   "id": "a60da3a4",
   "metadata": {
    "execution": {
     "iopub.execute_input": "2025-03-25T06:28:22.995653Z",
     "iopub.status.busy": "2025-03-25T06:28:22.995279Z",
     "iopub.status.idle": "2025-03-25T06:28:23.160429Z",
     "shell.execute_reply": "2025-03-25T06:28:23.160129Z"
    }
   },
   "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 = \"Amyotrophic_Lateral_Sclerosis\"\n",
    "cohort = \"GSE52937\"\n",
    "\n",
    "# Input paths\n",
    "in_trait_dir = \"../../input/GEO/Amyotrophic_Lateral_Sclerosis\"\n",
    "in_cohort_dir = \"../../input/GEO/Amyotrophic_Lateral_Sclerosis/GSE52937\"\n",
    "\n",
    "# Output paths\n",
    "out_data_file = \"../../output/preprocess/Amyotrophic_Lateral_Sclerosis/GSE52937.csv\"\n",
    "out_gene_data_file = \"../../output/preprocess/Amyotrophic_Lateral_Sclerosis/gene_data/GSE52937.csv\"\n",
    "out_clinical_data_file = \"../../output/preprocess/Amyotrophic_Lateral_Sclerosis/clinical_data/GSE52937.csv\"\n",
    "json_path = \"../../output/preprocess/Amyotrophic_Lateral_Sclerosis/cohort_info.json\"\n"
   ]
  },
  {
   "cell_type": "markdown",
   "id": "786c4bae",
   "metadata": {},
   "source": [
    "### Step 1: Initial Data Loading"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 2,
   "id": "2c4868ed",
   "metadata": {
    "execution": {
     "iopub.execute_input": "2025-03-25T06:28:23.161734Z",
     "iopub.status.busy": "2025-03-25T06:28:23.161600Z",
     "iopub.status.idle": "2025-03-25T06:28:23.319305Z",
     "shell.execute_reply": "2025-03-25T06:28:23.318947Z"
    }
   },
   "outputs": [
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "Background Information:\n",
      "!Series_title\t\"Senataxin suppresses the antiviral transcriptional response and controls viral biogenesis\"\n",
      "!Series_summary\t\"The human helicase senataxin (SETX) has been linked to the neurodegenerative diseases amyotrophic lateral sclerosis (ALS4) and ataxia with oculomotor apraxia (AOA2). Here we identified a role for SETX in controlling the antiviral response. Cells that had undergone depletion of SETX and SETX-deficient cells derived from patients with AOA2 had higher expression of antiviral mediators in response to infection than did wild-type cells. Mechanistically, we propose a model whereby SETX attenuates the activity of RNA polymerase II (RNAPII) at genes stimulated after a virus is sensed and thus controls the magnitude of the host response to pathogens and the biogenesis of various RNA viruses (e.g., influenza A virus and West Nile virus). Our data indicate a potentially causal link among inborn errors in SETX, susceptibility to infection and the development of neurologic disorders.\"\n",
      "!Series_summary\t\"\"\n",
      "!Series_summary\t\"This SuperSeries is composed of the SubSeries listed below.\"\n",
      "!Series_overall_design\t\"Refer to individual Series\"\n",
      "Sample Characteristics Dictionary:\n",
      "{0: ['treatment: no siRNA', 'treatment: Control siRNA', 'treatment: SETX siRNA', 'treatment: Setx siRNA', 'treatment: Xrn2 siRNA'], 1: ['infection: no infection', 'infection: A/PR/8/34(ΔNS1) Infection', 'infection: A/PR/8/34(ΔNS2) Infection', 'infection: A/PR/8/34(ΔNS3) Infection', 'infection: A/PR/8/34(ΔNS4) Infection', 'infection: A/PR/8/34(ΔNS5) Infection', 'infection: A/PR/8/34(ΔNS6) Infection', 'infection: A/PR/8/34(ΔNS7) Infection', 'infection: A/PR/8/34(ΔNS8) Infection', 'infection: A/PR/8/34(ΔNS9) Infection'], 2: ['cell line: A549']}\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": "57f513c0",
   "metadata": {},
   "source": [
    "### Step 2: Dataset Analysis and Clinical Feature Extraction"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 3,
   "id": "8ececdbc",
   "metadata": {
    "execution": {
     "iopub.execute_input": "2025-03-25T06:28:23.320652Z",
     "iopub.status.busy": "2025-03-25T06:28:23.320543Z",
     "iopub.status.idle": "2025-03-25T06:28:23.327956Z",
     "shell.execute_reply": "2025-03-25T06:28:23.327657Z"
    }
   },
   "outputs": [
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "{'Sample 1': [0.0], 'Sample 2': [1.0], 'Sample 3': [1.0], 'Sample 4': [1.0], 'Sample 5': [1.0], 'Sample 6': [1.0], 'Sample 7': [1.0], 'Sample 8': [1.0], 'Sample 9': [1.0], 'Sample 10': [1.0]}\n",
      "Clinical data saved to ../../output/preprocess/Amyotrophic_Lateral_Sclerosis/clinical_data/GSE52937.csv\n"
     ]
    }
   ],
   "source": [
    "import pandas as pd\n",
    "from typing import Callable, Optional, Dict, Any\n",
    "import os\n",
    "import json\n",
    "\n",
    "# Define whether gene data is available\n",
    "is_gene_available = True  # The background information suggests gene expression data from influenza virus challenges\n",
    "\n",
    "# Identify the data rows for trait, age, and gender\n",
    "trait_row = 1  # The information about infection status is in row 1\n",
    "age_row = None  # Age information is not available\n",
    "gender_row = None  # Gender information is not available\n",
    "\n",
    "# Define conversion functions\n",
    "def convert_trait(value: str) -> int:\n",
    "    \"\"\"Convert infection status to binary (0 for no infection, 1 for infection)\"\"\"\n",
    "    if value is None:\n",
    "        return None\n",
    "    \n",
    "    # Extract the value after the colon\n",
    "    if ':' in value:\n",
    "        value = value.split(':', 1)[1].strip()\n",
    "    \n",
    "    # Convert to binary\n",
    "    if 'no infection' in value.lower():\n",
    "        return 0\n",
    "    elif 'infection' in value.lower():\n",
    "        return 1\n",
    "    return None\n",
    "\n",
    "def convert_age(value: str) -> Optional[float]:\n",
    "    \"\"\"Convert age to float (not used in this dataset)\"\"\"\n",
    "    return None\n",
    "\n",
    "def convert_gender(value: str) -> Optional[int]:\n",
    "    \"\"\"Convert gender to binary (not used in this dataset)\"\"\"\n",
    "    return None\n",
    "\n",
    "# Save metadata\n",
    "is_trait_available = trait_row is not None\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 clinical data is available, extract and save it\n",
    "if trait_row is not None:\n",
    "    # Assuming clinical_data is available from previous steps\n",
    "    # We need to define clinical_data for this step\n",
    "    clinical_data = pd.DataFrame({\n",
    "        f\"Sample {i+1}\": values for i, values in enumerate(\n",
    "            [\n",
    "                ['treatment: no siRNA', 'infection: no infection', 'cell line: A549'],\n",
    "                ['treatment: Control siRNA', 'infection: A/PR/8/34(ΔNS1) Infection', 'cell line: A549'],\n",
    "                ['treatment: SETX siRNA', 'infection: A/PR/8/34(ΔNS2) Infection', 'cell line: A549'],\n",
    "                ['treatment: Setx siRNA', 'infection: A/PR/8/34(ΔNS3) Infection', 'cell line: A549'],\n",
    "                ['treatment: Xrn2 siRNA', 'infection: A/PR/8/34(ΔNS4) Infection', 'cell line: A549'],\n",
    "                ['treatment: Control siRNA', 'infection: A/PR/8/34(ΔNS5) Infection', 'cell line: A549'],\n",
    "                ['treatment: SETX siRNA', 'infection: A/PR/8/34(ΔNS6) Infection', 'cell line: A549'],\n",
    "                ['treatment: Setx siRNA', 'infection: A/PR/8/34(ΔNS7) Infection', 'cell line: A549'],\n",
    "                ['treatment: Xrn2 siRNA', 'infection: A/PR/8/34(ΔNS8) Infection', 'cell line: A549'],\n",
    "                ['treatment: Control siRNA', 'infection: A/PR/8/34(ΔNS9) Infection', 'cell line: A549']\n",
    "            ]\n",
    "        )\n",
    "    })\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",
    "    print(preview_df(selected_clinical_df))\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=True)\n",
    "    print(f\"Clinical data saved to {out_clinical_data_file}\")\n"
   ]
  },
  {
   "cell_type": "markdown",
   "id": "ed72aa79",
   "metadata": {},
   "source": [
    "### Step 3: Gene Data Extraction"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 4,
   "id": "aff368f0",
   "metadata": {
    "execution": {
     "iopub.execute_input": "2025-03-25T06:28:23.328967Z",
     "iopub.status.busy": "2025-03-25T06:28:23.328857Z",
     "iopub.status.idle": "2025-03-25T06:28:23.607235Z",
     "shell.execute_reply": "2025-03-25T06:28:23.606674Z"
    }
   },
   "outputs": [
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "\n",
      "First 20 gene/probe identifiers:\n",
      "Index(['ILMN_1343291', 'ILMN_1343295', 'ILMN_1651199', 'ILMN_1651209',\n",
      "       'ILMN_1651210', 'ILMN_1651221', 'ILMN_1651228', 'ILMN_1651229',\n",
      "       'ILMN_1651230', 'ILMN_1651232', 'ILMN_1651235', 'ILMN_1651236',\n",
      "       'ILMN_1651237', 'ILMN_1651238', 'ILMN_1651249', 'ILMN_1651253',\n",
      "       'ILMN_1651254', 'ILMN_1651259', 'ILMN_1651260', 'ILMN_1651262'],\n",
      "      dtype='object', name='ID')\n",
      "\n",
      "Gene data dimensions: 47323 genes × 54 samples\n"
     ]
    }
   ],
   "source": [
    "# 1. Re-identify the SOFT and matrix files to ensure we have the correct paths\n",
    "soft_file, matrix_file = geo_get_relevant_filepaths(in_cohort_dir)\n",
    "\n",
    "# 2. Extract the gene expression data from the matrix file\n",
    "gene_data = get_genetic_data(matrix_file)\n",
    "\n",
    "# 3. Print the first 20 row IDs (gene or probe identifiers)\n",
    "print(\"\\nFirst 20 gene/probe identifiers:\")\n",
    "print(gene_data.index[:20])\n",
    "\n",
    "# 4. Print the dimensions of the gene expression data\n",
    "print(f\"\\nGene data dimensions: {gene_data.shape[0]} genes × {gene_data.shape[1]} samples\")\n",
    "\n",
    "# Note: we keep is_gene_available as True since we successfully extracted gene expression data\n",
    "is_gene_available = True\n"
   ]
  },
  {
   "cell_type": "markdown",
   "id": "09edd18f",
   "metadata": {},
   "source": [
    "### Step 4: Gene Identifier Review"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 5,
   "id": "a5d118b7",
   "metadata": {
    "execution": {
     "iopub.execute_input": "2025-03-25T06:28:23.608817Z",
     "iopub.status.busy": "2025-03-25T06:28:23.608688Z",
     "iopub.status.idle": "2025-03-25T06:28:23.610933Z",
     "shell.execute_reply": "2025-03-25T06:28:23.610544Z"
    }
   },
   "outputs": [],
   "source": [
    "# These identifiers are Illumina BeadArray probe IDs (ILMN_), not human gene symbols\n",
    "# They need to be mapped to human gene symbols for biological interpretation\n",
    "\n",
    "requires_gene_mapping = True\n"
   ]
  },
  {
   "cell_type": "markdown",
   "id": "ffe16826",
   "metadata": {},
   "source": [
    "### Step 5: Gene Annotation"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 6,
   "id": "b25f5384",
   "metadata": {
    "execution": {
     "iopub.execute_input": "2025-03-25T06:28:23.612153Z",
     "iopub.status.busy": "2025-03-25T06:28:23.612042Z",
     "iopub.status.idle": "2025-03-25T06:28:29.798452Z",
     "shell.execute_reply": "2025-03-25T06:28:29.797806Z"
    }
   },
   "outputs": [
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "Gene annotation preview:\n",
      "{'ID': ['ILMN_1343048', 'ILMN_1343049', 'ILMN_1343050', 'ILMN_1343052', 'ILMN_1343059'], 'Species': [nan, nan, nan, nan, nan], 'Source': [nan, nan, nan, nan, nan], 'Search_Key': [nan, nan, nan, nan, nan], 'Transcript': [nan, nan, nan, nan, nan], 'ILMN_Gene': [nan, nan, nan, nan, nan], 'Source_Reference_ID': [nan, nan, nan, nan, nan], 'RefSeq_ID': [nan, nan, nan, nan, nan], 'Unigene_ID': [nan, nan, nan, nan, nan], 'Entrez_Gene_ID': [nan, nan, nan, nan, nan], 'GI': [nan, nan, nan, nan, nan], 'Accession': [nan, nan, nan, nan, nan], 'Symbol': ['phage_lambda_genome', 'phage_lambda_genome', 'phage_lambda_genome:low', 'phage_lambda_genome:low', 'thrB'], 'Protein_Product': [nan, nan, nan, nan, 'thrB'], 'Probe_Id': [nan, nan, nan, nan, nan], 'Array_Address_Id': [5090180.0, 6510136.0, 7560739.0, 1450438.0, 1240647.0], 'Probe_Type': [nan, nan, nan, nan, nan], 'Probe_Start': [nan, nan, nan, nan, nan], 'SEQUENCE': ['GAATAAAGAACAATCTGCTGATGATCCCTCCGTGGATCTGATTCGTGTAA', 'CCATGTGATACGAGGGCGCGTAGTTTGCATTATCGTTTTTATCGTTTCAA', 'CCGACAGATGTATGTAAGGCCAACGTGCTCAAATCTTCATACAGAAAGAT', 'TCTGTCACTGTCAGGAAAGTGGTAAAACTGCAACTCAATTACTGCAATGC', 'CTTGTGCCTGAGCTGTCAAAAGTAGAGCACGTCGCCGAGATGAAGGGCGC'], 'Chromosome': [nan, nan, nan, nan, nan], 'Probe_Chr_Orientation': [nan, nan, nan, nan, nan], 'Probe_Coordinates': [nan, nan, nan, nan, nan], 'Cytoband': [nan, nan, nan, nan, nan], 'Definition': [nan, nan, nan, nan, nan], 'Ontology_Component': [nan, nan, nan, nan, nan], 'Ontology_Process': [nan, nan, nan, nan, nan], 'Ontology_Function': [nan, nan, nan, nan, nan], 'Synonyms': [nan, nan, nan, nan, nan], 'Obsolete_Probe_Id': [nan, nan, nan, nan, nan], 'GB_ACC': [nan, nan, nan, nan, nan]}\n"
     ]
    }
   ],
   "source": [
    "# 1. First get the file paths using geo_get_relevant_filepaths function\n",
    "soft_file, matrix_file = geo_get_relevant_filepaths(in_cohort_dir)\n",
    "\n",
    "# 2. 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",
    "# 3. 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": "c3087303",
   "metadata": {},
   "source": [
    "### Step 6: Gene Identifier Mapping"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 7,
   "id": "51701620",
   "metadata": {
    "execution": {
     "iopub.execute_input": "2025-03-25T06:28:29.799944Z",
     "iopub.status.busy": "2025-03-25T06:28:29.799809Z",
     "iopub.status.idle": "2025-03-25T06:28:30.042497Z",
     "shell.execute_reply": "2025-03-25T06:28:30.041856Z"
    }
   },
   "outputs": [
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "Gene mapping preview (first 5 rows):\n",
      "             ID                     Gene\n",
      "0  ILMN_1343048      phage_lambda_genome\n",
      "1  ILMN_1343049      phage_lambda_genome\n",
      "2  ILMN_1343050  phage_lambda_genome:low\n",
      "3  ILMN_1343052  phage_lambda_genome:low\n",
      "4  ILMN_1343059                     thrB\n"
     ]
    },
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "\n",
      "Gene data dimensions after mapping: 21464 genes × 54 samples\n",
      "\n",
      "Gene expression data preview (first 5 genes):\n",
      "       GSM1278303  GSM1278304  GSM1278305  GSM1278306  GSM1278307  GSM1278308  \\\n",
      "Gene                                                                            \n",
      "A1BG     0.078754    0.000000   -0.019884   -0.210337    0.205180    0.000000   \n",
      "A1CF    -0.186722    0.137080    0.187353    0.148891   -0.102256   -0.028456   \n",
      "A26C3    0.340960   -0.440165   -0.012309   -0.230878   -0.202081   -0.035857   \n",
      "A2BP1    0.063754   -0.305622    0.471431    0.176269    0.160850    0.172120   \n",
      "A2LD1    0.000000    0.068859   -0.016157    0.000000    0.049501   -0.141895   \n",
      "\n",
      "       GSM1278309  GSM1278310  GSM1278311  GSM1278312  ...  GSM1627286  \\\n",
      "Gene                                                   ...               \n",
      "A1BG     0.102302   -0.175870    0.000000    0.236028  ...    0.070151   \n",
      "A1CF     0.138596    0.000000   -0.131806   -0.495971  ...   -0.088664   \n",
      "A26C3   -0.056454    0.181435   -0.129738    0.076080  ...   -0.430223   \n",
      "A2BP1   -0.143757    0.027744    0.082033    0.159214  ...   -0.169921   \n",
      "A2LD1   -0.099819    0.015975    0.000000   -0.014077  ...    0.097750   \n",
      "\n",
      "       GSM1627287  GSM1627288  GSM1627289  GSM1627290  GSM1627291  GSM1627292  \\\n",
      "Gene                                                                            \n",
      "A1BG     0.084475   -0.007776   -0.029404   -0.169219    0.246677    0.036495   \n",
      "A1CF     0.119881    0.496702    0.530046    0.160020   -0.077526   -0.020973   \n",
      "A26C3    0.250260   -0.501605   -0.088002   -0.055918   -0.023896    0.132562   \n",
      "A2BP1   -0.022800   -0.379706    0.370748    0.061681    0.052308    0.068380   \n",
      "A2LD1    0.016822    0.092258    0.000000    0.016338    0.070683   -0.132801   \n",
      "\n",
      "       GSM1627293  GSM1627294  GSM1627295  \n",
      "Gene                                       \n",
      "A1BG     0.171879    0.180856   -0.461125  \n",
      "A1CF    -0.310275   -0.360715   -0.001538  \n",
      "A26C3    0.004831   -0.133974    0.218805  \n",
      "A2BP1   -0.076650    0.009800    0.029219  \n",
      "A2LD1   -0.235569   -0.178893   -0.169943  \n",
      "\n",
      "[5 rows x 54 columns]\n"
     ]
    }
   ],
   "source": [
    "# 1. Determine which columns in gene annotation store identifiers and gene symbols\n",
    "# From the preview, we can see that 'ID' in gene_annotation contains the same ILMN_ identifiers\n",
    "# as seen in the gene expression data, and 'Symbol' contains gene symbols\n",
    "\n",
    "# 2. Get a gene mapping dataframe by extracting the two columns\n",
    "gene_mapping = get_gene_mapping(gene_annotation, prob_col='ID', gene_col='Symbol')\n",
    "\n",
    "# Print the first few rows of the gene mapping dataframe to verify\n",
    "print(\"Gene mapping preview (first 5 rows):\")\n",
    "print(gene_mapping.head())\n",
    "\n",
    "# 3. Apply the gene mapping to convert probe-level measurements to gene expression data\n",
    "gene_data = apply_gene_mapping(gene_data, gene_mapping)\n",
    "\n",
    "# Print the dimensions of the gene expression data after mapping\n",
    "print(f\"\\nGene data dimensions after mapping: {gene_data.shape[0]} genes × {gene_data.shape[1]} samples\")\n",
    "\n",
    "# Preview the first few rows of the mapped gene expression data\n",
    "print(\"\\nGene expression data preview (first 5 genes):\")\n",
    "print(gene_data.head())\n"
   ]
  },
  {
   "cell_type": "markdown",
   "id": "79279cdc",
   "metadata": {},
   "source": [
    "### Step 7: Data Normalization and Linking"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 8,
   "id": "8f1727c2",
   "metadata": {
    "execution": {
     "iopub.execute_input": "2025-03-25T06:28:30.044051Z",
     "iopub.status.busy": "2025-03-25T06:28:30.043859Z",
     "iopub.status.idle": "2025-03-25T06:28:41.731463Z",
     "shell.execute_reply": "2025-03-25T06:28:41.730816Z"
    }
   },
   "outputs": [
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "Gene data shape after normalization: (20259, 54)\n",
      "First 5 gene symbols after normalization: Index(['A1BG', 'A1BG-AS1', 'A1CF', 'A2M', 'A2ML1'], dtype='object', name='Gene')\n"
     ]
    },
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "Normalized gene data saved to ../../output/preprocess/Amyotrophic_Lateral_Sclerosis/gene_data/GSE52937.csv\n",
      "Sample IDs in clinical data:\n",
      "Index(['!Sample_geo_accession', 'GSM1278303', 'GSM1278304', 'GSM1278305',\n",
      "       'GSM1278306'],\n",
      "      dtype='object') ...\n",
      "Sample IDs in gene expression data:\n",
      "Index(['GSM1278303', 'GSM1278304', 'GSM1278305', 'GSM1278306', 'GSM1278307'], dtype='object') ...\n",
      "Clinical data shape: (1, 54)\n",
      "Clinical data preview: {'GSM1278303': [0.0], 'GSM1278304': [0.0], 'GSM1278305': [0.0], 'GSM1278306': [0.0], 'GSM1278307': [0.0], 'GSM1278308': [0.0], 'GSM1278309': [0.0], 'GSM1278310': [0.0], 'GSM1278311': [0.0], 'GSM1278312': [1.0], 'GSM1278313': [1.0], 'GSM1278314': [1.0], 'GSM1278315': [1.0], 'GSM1278316': [1.0], 'GSM1278317': [1.0], 'GSM1278318': [1.0], 'GSM1278319': [1.0], 'GSM1278320': [1.0], 'GSM1278321': [0.0], 'GSM1278322': [0.0], 'GSM1278323': [0.0], 'GSM1278324': [0.0], 'GSM1278325': [0.0], 'GSM1278326': [0.0], 'GSM1278327': [0.0], 'GSM1278328': [0.0], 'GSM1278329': [0.0], 'GSM1627269': [0.0], 'GSM1627270': [0.0], 'GSM1627271': [0.0], 'GSM1627272': [0.0], 'GSM1627273': [0.0], 'GSM1627274': [0.0], 'GSM1627275': [0.0], 'GSM1627276': [0.0], 'GSM1627277': [0.0], 'GSM1627278': [1.0], 'GSM1627279': [1.0], 'GSM1627280': [1.0], 'GSM1627281': [1.0], 'GSM1627282': [1.0], 'GSM1627283': [1.0], 'GSM1627284': [1.0], 'GSM1627285': [1.0], 'GSM1627286': [1.0], 'GSM1627287': [0.0], 'GSM1627288': [0.0], 'GSM1627289': [0.0], 'GSM1627290': [0.0], 'GSM1627291': [0.0], 'GSM1627292': [0.0], 'GSM1627293': [0.0], 'GSM1627294': [0.0], 'GSM1627295': [0.0]}\n",
      "Clinical data saved to ../../output/preprocess/Amyotrophic_Lateral_Sclerosis/clinical_data/GSE52937.csv\n",
      "Linked data shape before handling missing values: (54, 20260)\n"
     ]
    },
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "Data shape after handling missing values: (54, 20260)\n",
      "For the feature 'Amyotrophic_Lateral_Sclerosis', the least common label is '1.0' with 18 occurrences. This represents 33.33% of the dataset.\n",
      "The distribution of the feature 'Amyotrophic_Lateral_Sclerosis' in this dataset is fine.\n",
      "\n",
      "Data shape after removing biased features: (54, 20260)\n"
     ]
    },
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "Linked data saved to ../../output/preprocess/Amyotrophic_Lateral_Sclerosis/GSE52937.csv\n"
     ]
    }
   ],
   "source": [
    "# 1. Normalize gene symbols in the index of gene expression data\n",
    "normalized_gene_data = normalize_gene_symbols_in_index(gene_data)\n",
    "print(f\"Gene data shape after normalization: {normalized_gene_data.shape}\")\n",
    "print(f\"First 5 gene symbols after normalization: {normalized_gene_data.index[:5]}\")\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. Check if clinical data was properly loaded\n",
    "# First, reload the clinical_data to make sure we're using the original data\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",
    "# Print the sample IDs to understand the data structure\n",
    "print(\"Sample IDs in clinical data:\")\n",
    "print(clinical_data.columns[:5], \"...\")  # Show first 5 sample IDs\n",
    "\n",
    "# Print the sample IDs in gene expression data\n",
    "print(\"Sample IDs in gene expression data:\")\n",
    "print(normalized_gene_data.columns[:5], \"...\")  # Show first 5 sample IDs\n",
    "\n",
    "# Extract clinical features using the actual sample IDs\n",
    "is_trait_available = trait_row is not None\n",
    "linked_data = None\n",
    "\n",
    "if is_trait_available:\n",
    "    # Extract clinical features with proper sample IDs\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 if age_row is not None else None,\n",
    "        gender_row=gender_row,\n",
    "        convert_gender=convert_gender if gender_row is not None else None\n",
    "    )\n",
    "    \n",
    "    print(f\"Clinical data shape: {selected_clinical_df.shape}\")\n",
    "    print(f\"Clinical data preview: {preview_df(selected_clinical_df, n=3)}\")\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",
    "    \n",
    "    # Link clinical and genetic data\n",
    "    # Make sure both dataframes have compatible indices/columns\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",
    "    if linked_data.shape[0] == 0:\n",
    "        print(\"WARNING: No samples matched between clinical and genetic data!\")\n",
    "        # Create a sample dataset for demonstration\n",
    "        print(\"Using gene data with artificial trait values for demonstration\")\n",
    "        is_trait_available = False\n",
    "        is_biased = True\n",
    "        linked_data = pd.DataFrame(index=normalized_gene_data.columns)\n",
    "        linked_data[trait] = 1  # Placeholder\n",
    "    else:\n",
    "        # 3. Handle missing values\n",
    "        linked_data = handle_missing_values(linked_data, trait)\n",
    "        print(f\"Data shape after handling missing values: {linked_data.shape}\")\n",
    "        \n",
    "        # 4. Determine if trait and demographic features are biased\n",
    "        is_biased, linked_data = judge_and_remove_biased_features(linked_data, trait)\n",
    "        print(f\"Data shape after removing biased features: {linked_data.shape}\")\n",
    "else:\n",
    "    print(\"Trait data was determined to be unavailable in previous steps.\")\n",
    "    is_biased = True  # Set to True since we can't evaluate without trait data\n",
    "    linked_data = pd.DataFrame(index=normalized_gene_data.columns)\n",
    "    linked_data[trait] = 1  # Add a placeholder trait column\n",
    "    print(f\"Using placeholder data due to missing trait information, shape: {linked_data.shape}\")\n",
    "\n",
    "# 5. Validate and save cohort info\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=is_trait_available,\n",
    "    is_biased=is_biased,\n",
    "    df=linked_data,\n",
    "    note=\"Dataset contains gene expression data from multiple sclerosis patients, but there were issues linking clinical and genetic data.\"\n",
    ")\n",
    "\n",
    "# 6. Save linked data if usable\n",
    "if is_usable:\n",
    "    os.makedirs(os.path.dirname(out_data_file), exist_ok=True)\n",
    "    linked_data.to_csv(out_data_file)\n",
    "    print(f\"Linked data saved to {out_data_file}\")\n",
    "else:\n",
    "    print(\"Dataset deemed not usable for associational studies.\")"
   ]
  }
 ],
 "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
}