File size: 50,725 Bytes
9fe78b4
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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
687
688
689
690
691
692
693
694
695
696
697
698
699
700
701
702
703
704
705
706
707
708
709
710
711
712
713
714
715
716
717
718
719
720
721
722
723
724
725
726
727
728
729
730
731
732
733
734
735
736
737
738
739
740
741
742
743
744
745
746
747
748
749
750
751
752
753
754
755
756
757
758
759
760
761
762
763
764
765
766
767
768
769
770
771
772
773
774
775
776
777
778
779
780
781
782
783
784
785
786
787
788
789
790
791
792
793
794
795
796
797
798
799
800
801
802
803
804
805
806
807
808
809
810
811
812
813
814
815
816
817
818
819
820
821
822
823
824
825
826
827
828
829
830
831
832
833
834
835
836
837
838
839
840
841
842
843
844
845
846
847
848
849
850
851
852
853
854
855
856
857
858
859
860
861
862
863
864
865
866
867
868
869
870
871
872
873
874
875
876
877
878
879
880
881
882
883
884
885
886
887
888
889
890
891
892
893
894
895
896
897
898
899
900
901
902
903
904
905
906
907
908
909
910
911
912
913
914
915
916
917
918
919
920
921
922
923
924
925
926
927
928
929
930
931
932
933
934
935
936
937
938
939
940
941
942
943
944
945
946
947
948
949
950
951
952
953
954
955
956
957
958
959
960
961
962
963
964
965
966
967
968
969
970
971
972
973
974
975
976
977
978
979
980
981
982
983
984
985
986
987
988
989
990
991
992
993
994
995
996
997
998
999
1000
1001
1002
1003
1004
1005
1006
1007
1008
1009
1010
1011
{
 "cells": [
  {
   "cell_type": "code",
   "execution_count": 1,
   "id": "2142ee66",
   "metadata": {
    "execution": {
     "iopub.execute_input": "2025-03-25T04:32:35.603596Z",
     "iopub.status.busy": "2025-03-25T04:32:35.603370Z",
     "iopub.status.idle": "2025-03-25T04:32:35.780921Z",
     "shell.execute_reply": "2025-03-25T04:32:35.780575Z"
    }
   },
   "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 = \"Uterine_Corpus_Endometrial_Carcinoma\"\n",
    "cohort = \"GSE32507\"\n",
    "\n",
    "# Input paths\n",
    "in_trait_dir = \"../../input/GEO/Uterine_Corpus_Endometrial_Carcinoma\"\n",
    "in_cohort_dir = \"../../input/GEO/Uterine_Corpus_Endometrial_Carcinoma/GSE32507\"\n",
    "\n",
    "# Output paths\n",
    "out_data_file = \"../../output/preprocess/Uterine_Corpus_Endometrial_Carcinoma/GSE32507.csv\"\n",
    "out_gene_data_file = \"../../output/preprocess/Uterine_Corpus_Endometrial_Carcinoma/gene_data/GSE32507.csv\"\n",
    "out_clinical_data_file = \"../../output/preprocess/Uterine_Corpus_Endometrial_Carcinoma/clinical_data/GSE32507.csv\"\n",
    "json_path = \"../../output/preprocess/Uterine_Corpus_Endometrial_Carcinoma/cohort_info.json\"\n"
   ]
  },
  {
   "cell_type": "markdown",
   "id": "b8991e42",
   "metadata": {},
   "source": [
    "### Step 1: Initial Data Loading"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 2,
   "id": "51caf6a0",
   "metadata": {
    "execution": {
     "iopub.execute_input": "2025-03-25T04:32:35.782307Z",
     "iopub.status.busy": "2025-03-25T04:32:35.782177Z",
     "iopub.status.idle": "2025-03-25T04:32:35.921413Z",
     "shell.execute_reply": "2025-03-25T04:32:35.921121Z"
    }
   },
   "outputs": [
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "Files in the cohort directory:\n",
      "['GSE32507_family.soft.gz', 'GSE32507_series_matrix.txt.gz']\n",
      "Identified SOFT files: ['GSE32507_family.soft.gz']\n",
      "Identified matrix files: ['GSE32507_series_matrix.txt.gz']\n",
      "\n",
      "Background Information:\n",
      "!Series_title\t\"Expression profile of carcinosarcoma (CS), endometrioid adenocarcinoma (EC) and sarcoma (US) of uterine corpus\"\n",
      "!Series_summary\t\"To examine the simlarity of CS, EC and US, we performed microarray analysis of frozen tissues of 46 patients (14 CS, 24 EC and 8 US).\"\n",
      "!Series_overall_design\t\"Frozen tissues of 46 patients (14CS, 24EC and 8US) were subjected to cDNA microarray analysis.\"\n",
      "\n",
      "Sample Characteristics Dictionary:\n",
      "{0: ['tissue: carcinosarcoma', 'tissue: endometrioid adenocarcinoma', 'tissue: sarcoma'], 1: ['carcinosarcoma status: : heterologous', 'carcinosarcoma status: : homologous', nan]}\n"
     ]
    }
   ],
   "source": [
    "# 1. Let's first list the directory contents to understand what files are available\n",
    "import os\n",
    "\n",
    "print(\"Files in the cohort directory:\")\n",
    "files = os.listdir(in_cohort_dir)\n",
    "print(files)\n",
    "\n",
    "# Adapt file identification to handle different naming patterns\n",
    "soft_files = [f for f in files if 'soft' in f.lower() or '.soft' in f.lower() or '_soft' in f.lower()]\n",
    "matrix_files = [f for f in files if 'matrix' in f.lower() or '.matrix' in f.lower() or '_matrix' in f.lower()]\n",
    "\n",
    "# If no files with these patterns are found, look for alternative file types\n",
    "if not soft_files:\n",
    "    soft_files = [f for f in files if f.endswith('.txt') or f.endswith('.gz')]\n",
    "if not matrix_files:\n",
    "    matrix_files = [f for f in files if f.endswith('.txt') or f.endswith('.gz')]\n",
    "\n",
    "print(\"Identified SOFT files:\", soft_files)\n",
    "print(\"Identified matrix files:\", matrix_files)\n",
    "\n",
    "# Use the first files found, if any\n",
    "if len(soft_files) > 0 and len(matrix_files) > 0:\n",
    "    soft_file = os.path.join(in_cohort_dir, soft_files[0])\n",
    "    matrix_file = os.path.join(in_cohort_dir, matrix_files[0])\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(\"\\nBackground Information:\")\n",
    "    print(background_info)\n",
    "    print(\"\\nSample Characteristics Dictionary:\")\n",
    "    print(sample_characteristics_dict)\n",
    "else:\n",
    "    print(\"No appropriate files found in the directory.\")\n"
   ]
  },
  {
   "cell_type": "markdown",
   "id": "5c881d32",
   "metadata": {},
   "source": [
    "### Step 2: Dataset Analysis and Clinical Feature Extraction"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 3,
   "id": "7163b15f",
   "metadata": {
    "execution": {
     "iopub.execute_input": "2025-03-25T04:32:35.922569Z",
     "iopub.status.busy": "2025-03-25T04:32:35.922469Z",
     "iopub.status.idle": "2025-03-25T04:32:35.931284Z",
     "shell.execute_reply": "2025-03-25T04:32:35.931010Z"
    }
   },
   "outputs": [
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "Original trait values:\n",
      "  \"tissue: carcinosarcoma\"\n",
      "  \"tissue: endometrioid adenocarcinoma\"\n",
      "  \"tissue: sarcoma\"\n",
      "Preview of selected clinical features:\n",
      "{'Sample_ID': [0.0], 'characteristics_ch1': [0.0]}\n",
      "Clinical data saved to ../../output/preprocess/Uterine_Corpus_Endometrial_Carcinoma/clinical_data/GSE32507.csv\n"
     ]
    }
   ],
   "source": [
    "# Check availability of gene expression data\n",
    "# This dataset seems to contain gene expression data based on the background information\n",
    "# mentioning \"cDNA microarray analysis\", so set is_gene_available to True\n",
    "is_gene_available = True\n",
    "\n",
    "# Variable availability and data type conversion\n",
    "# 1. Trait availability: based on the sample characteristics, tissue type is at key 0\n",
    "# which differentiates between carcinosarcoma, endometrioid adenocarcinoma, and sarcoma\n",
    "trait_row = 0\n",
    "\n",
    "# 2. Age data: not available in sample characteristics\n",
    "age_row = None\n",
    "\n",
    "# 3. Gender data: not available, and since this is a study about uterine corpus,\n",
    "# we can assume all patients are female (but we'll set it as unavailable since it's a constant)\n",
    "gender_row = None\n",
    "\n",
    "# Define conversion functions for each variable\n",
    "def convert_trait(value):\n",
    "    \"\"\"Convert the trait value to a binary variable.\n",
    "    Since we're focused on Uterine_Corpus_Endometrial_Carcinoma, we'll consider\n",
    "    'endometrioid adenocarcinoma' as our positive class (1) and other types as negative (0).\n",
    "    \"\"\"\n",
    "    if pd.isna(value):\n",
    "        return None\n",
    "    \n",
    "    # Extract the value if it contains a colon\n",
    "    if ':' in value:\n",
    "        value = value.split(':', 1)[1].strip()\n",
    "    \n",
    "    if 'endometrioid adenocarcinoma' in value.lower():\n",
    "        return 1\n",
    "    else:  # carcinosarcoma or sarcoma\n",
    "        return 0\n",
    "\n",
    "def convert_age(value):\n",
    "    \"\"\"Placeholder function for converting age.\"\"\"\n",
    "    return None  # Not used as age data is not available\n",
    "\n",
    "def convert_gender(value):\n",
    "    \"\"\"Placeholder function for converting gender.\"\"\"\n",
    "    return None  # Not used as gender data is not available\n",
    "\n",
    "# Check if trait data is available\n",
    "is_trait_available = trait_row is not None\n",
    "\n",
    "# Save 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",
    "# Extract clinical features if trait data is available\n",
    "if is_trait_available:\n",
    "    try:\n",
    "        # Load all sample characteristics from the matrix file\n",
    "        matrix_file = f\"{in_cohort_dir}/GSE32507_series_matrix.txt.gz\"\n",
    "        \n",
    "        # Create a dictionary to store sample information\n",
    "        sample_data = {}\n",
    "        current_sample_idx = -1\n",
    "        sample_ids = []\n",
    "        \n",
    "        with gzip.open(matrix_file, 'rt') as file:\n",
    "            for line in file:\n",
    "                line = line.strip()\n",
    "                \n",
    "                # Extract sample GEO IDs\n",
    "                if line.startswith('!Sample_geo_accession'):\n",
    "                    sample_ids = line.split('\\t')[1:]\n",
    "                    for idx, sample_id in enumerate(sample_ids):\n",
    "                        sample_data[sample_id] = {}\n",
    "                \n",
    "                # Extract characteristics\n",
    "                elif line.startswith('!Sample_characteristics_ch1'):\n",
    "                    characteristics = line.split('\\t')[1:]\n",
    "                    \n",
    "                    # Match each characteristic to its corresponding sample\n",
    "                    for idx, characteristic in enumerate(characteristics):\n",
    "                        if idx < len(sample_ids):\n",
    "                            sample_id = sample_ids[idx]\n",
    "                            \n",
    "                            # Append to list of characteristics for this sample\n",
    "                            if 'characteristics' not in sample_data[sample_id]:\n",
    "                                sample_data[sample_id]['characteristics'] = []\n",
    "                            \n",
    "                            sample_data[sample_id]['characteristics'].append(characteristic)\n",
    "                \n",
    "                # If we've processed all sample data, stop reading\n",
    "                elif line.startswith('!series_matrix_table_begin'):\n",
    "                    break\n",
    "        \n",
    "        # Create a DataFrame to represent our clinical data\n",
    "        clinical_rows = []\n",
    "        \n",
    "        # For each row in the trait_row (key 0 in the sample characteristics)\n",
    "        for sample_id, data in sample_data.items():\n",
    "            if 'characteristics' in data and len(data['characteristics']) > trait_row:\n",
    "                trait_value = data['characteristics'][trait_row]\n",
    "                clinical_rows.append({\n",
    "                    'Sample_ID': sample_id,\n",
    "                    'characteristics_ch1': trait_value\n",
    "                })\n",
    "        \n",
    "        clinical_df = pd.DataFrame(clinical_rows)\n",
    "        \n",
    "        if not clinical_df.empty:\n",
    "            # Print original values for debugging\n",
    "            print(\"Original trait values:\")\n",
    "            for val in clinical_df['characteristics_ch1'].unique():\n",
    "                print(f\"  {val}\")\n",
    "            \n",
    "            # Extract clinical features\n",
    "            selected_clinical_df = geo_select_clinical_features(\n",
    "                clinical_df=clinical_df,\n",
    "                trait=trait,\n",
    "                trait_row=0,  # Use 0 here because we've already extracted the trait row\n",
    "                convert_trait=convert_trait,\n",
    "                age_row=None,\n",
    "                convert_age=None,\n",
    "                gender_row=None,\n",
    "                convert_gender=None\n",
    "            )\n",
    "            \n",
    "            # Preview the data\n",
    "            preview = preview_df(selected_clinical_df)\n",
    "            print(\"Preview of selected clinical features:\")\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",
    "        else:\n",
    "            print(\"No clinical data found in the matrix file.\")\n",
    "    except Exception as e:\n",
    "        print(f\"Error extracting or saving clinical features: {e}\")\n",
    "        import traceback\n",
    "        traceback.print_exc()\n"
   ]
  },
  {
   "cell_type": "markdown",
   "id": "26a3e09a",
   "metadata": {},
   "source": [
    "### Step 3: Gene Data Extraction"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 4,
   "id": "1d33866a",
   "metadata": {
    "execution": {
     "iopub.execute_input": "2025-03-25T04:32:35.932306Z",
     "iopub.status.busy": "2025-03-25T04:32:35.932205Z",
     "iopub.status.idle": "2025-03-25T04:32:36.153825Z",
     "shell.execute_reply": "2025-03-25T04:32:36.153458Z"
    }
   },
   "outputs": [
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "First 20 gene/probe identifiers:\n",
      "Index(['(+)E1A_r60_1', '(+)E1A_r60_3', '(+)E1A_r60_a104', '(+)E1A_r60_a107',\n",
      "       '(+)E1A_r60_a135', '(+)E1A_r60_a20', '(+)E1A_r60_a22', '(+)E1A_r60_a97',\n",
      "       '(+)E1A_r60_n11', '(+)E1A_r60_n9', '(+)eQC-39', '(+)eQC-41',\n",
      "       '(+)eQC-42', '(-)3xSLv1', 'A_23_P100001', 'A_23_P100011',\n",
      "       'A_23_P100022', 'A_23_P100056', 'A_23_P100074', 'A_23_P100092'],\n",
      "      dtype='object', name='ID')\n",
      "\n",
      "Gene expression data shape: (41073, 46)\n"
     ]
    }
   ],
   "source": [
    "# Use the helper function to get the proper file paths\n",
    "soft_file_path, matrix_file_path = geo_get_relevant_filepaths(in_cohort_dir)\n",
    "\n",
    "# Extract gene expression data\n",
    "try:\n",
    "    gene_data = get_genetic_data(matrix_file_path)\n",
    "    \n",
    "    # Print the first 20 row IDs (gene or probe identifiers)\n",
    "    print(\"First 20 gene/probe identifiers:\")\n",
    "    print(gene_data.index[:20])\n",
    "    \n",
    "    # Print shape to understand the dataset dimensions\n",
    "    print(f\"\\nGene expression data shape: {gene_data.shape}\")\n",
    "    \n",
    "except Exception as e:\n",
    "    print(f\"Error extracting gene data: {e}\")\n"
   ]
  },
  {
   "cell_type": "markdown",
   "id": "211ae49e",
   "metadata": {},
   "source": [
    "### Step 4: Gene Identifier Review"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 5,
   "id": "57f28652",
   "metadata": {
    "execution": {
     "iopub.execute_input": "2025-03-25T04:32:36.155076Z",
     "iopub.status.busy": "2025-03-25T04:32:36.154963Z",
     "iopub.status.idle": "2025-03-25T04:32:36.156832Z",
     "shell.execute_reply": "2025-03-25T04:32:36.156558Z"
    }
   },
   "outputs": [],
   "source": [
    "# Looking at the gene identifiers in the gene expression data\n",
    "# The identifiers (e.g., \"A_23_P100001\") appear to be Agilent microarray probe IDs, not standard human gene symbols\n",
    "# These probe IDs need to be mapped to official gene symbols for proper analysis\n",
    "\n",
    "requires_gene_mapping = True\n"
   ]
  },
  {
   "cell_type": "markdown",
   "id": "640808c8",
   "metadata": {},
   "source": [
    "### Step 5: Gene Annotation"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 6,
   "id": "b4477218",
   "metadata": {
    "execution": {
     "iopub.execute_input": "2025-03-25T04:32:36.157941Z",
     "iopub.status.busy": "2025-03-25T04:32:36.157846Z",
     "iopub.status.idle": "2025-03-25T04:32:40.427626Z",
     "shell.execute_reply": "2025-03-25T04:32:40.427259Z"
    }
   },
   "outputs": [
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "Sample of gene expression data (first 5 rows, first 5 columns):\n",
      "                 GSM804806  GSM804807  GSM804808  GSM804809  GSM804810\n",
      "ID                                                                    \n",
      "(+)E1A_r60_1      0.187544   1.125378   0.308133   1.549022   0.297386\n",
      "(+)E1A_r60_3     -0.057653   0.098557  -0.019575   2.112438   0.290960\n",
      "(+)E1A_r60_a104   0.309965   0.280072  -0.410076   1.748169  -0.370941\n",
      "(+)E1A_r60_a107   0.291783   1.178800  -0.036704   1.191367   0.090694\n",
      "(+)E1A_r60_a135   0.274253   1.303301   0.063972   1.639965   0.304410\n"
     ]
    },
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "\n",
      "Platform information:\n",
      "!Series_title = Expression profile of carcinosarcoma (CS), endometrioid adenocarcinoma (EC) and sarcoma (US) of uterine corpus\n",
      "!Platform_title = Agilent-014850 Whole Human Genome Microarray 4x44K G4112F (Probe Name version)\n",
      "!Platform_description = This multi-pack (4X44K) formatted microarray represents a compiled view of the human genome as it is understood today. The sequence information used to design this product was derived from a broad survey of well known sources such as RefSeq, Goldenpath, Ensembl, Unigene and others. The resulting view of the human genome covers 41K unique genes and transcripts which have been verified and optimized by alignment to the human genome assembly and by Agilent's Empirical Validation process.\n",
      "!Platform_description =\n",
      "!Platform_description = *** The ID column includes the Agilent Probe Names. A different version of this platform with the Agilent Feature Extraction feature numbers in the ID column is assigned accession number GPL4133\n",
      "#DESCRIPTION = Description\n",
      "ID\tSPOT_ID\tCONTROL_TYPE\tREFSEQ\tGB_ACC\tGENE\tGENE_SYMBOL\tGENE_NAME\tUNIGENE_ID\tENSEMBL_ID\tTIGR_ID\tACCESSION_STRING\tCHROMOSOMAL_LOCATION\tCYTOBAND\tDESCRIPTION\tGO_ID\tSEQUENCE\n",
      "!Sample_description = Gene expression data from frozen tumor samples\n",
      "!Sample_description = Gene expression data from frozen tumor samples\n",
      "!Sample_description = Gene expression data from frozen tumor samples\n",
      "!Sample_description = Gene expression data from frozen tumor samples\n",
      "!Sample_description = Gene expression data from frozen tumor samples\n",
      "!Sample_description = Gene expression data from frozen tumor samples\n",
      "!Sample_description = Gene expression data from frozen tumor samples\n",
      "!Sample_description = Gene expression data from frozen tumor samples\n",
      "!Sample_description = Gene expression data from frozen tumor samples\n",
      "!Sample_description = Gene expression data from frozen tumor samples\n",
      "!Sample_description = Gene expression data from frozen tumor samples\n",
      "!Sample_description = Gene expression data from frozen tumor samples\n",
      "!Sample_description = Gene expression data from frozen tumor samples\n",
      "!Sample_description = Gene expression data from frozen tumor samples\n",
      "!Sample_description = Gene expression data from frozen tumor samples\n",
      "!Sample_description = Gene expression data from frozen tumor samples\n",
      "!Sample_description = Gene expression data from frozen tumor samples\n",
      "!Sample_description = Gene expression data from frozen tumor samples\n",
      "!Sample_description = Gene expression data from frozen tumor samples\n",
      "!Sample_description = Gene expression data from frozen tumor samples\n",
      "!Sample_description = Gene expression data from frozen tumor samples\n",
      "!Sample_description = Gene expression data from frozen tumor samples\n",
      "!Sample_description = Gene expression data from frozen tumor samples\n",
      "!Sample_description = Gene expression data from frozen tumor samples\n",
      "!Sample_description = Gene expression data from frozen tumor samples\n",
      "!Sample_description = Gene expression data from frozen tumor samples\n",
      "!Sample_description = Gene expression data from frozen tumor samples\n",
      "!Sample_description = Gene expression data from frozen tumor samples\n",
      "!Sample_description = Gene expression data from frozen tumor samples\n",
      "!Sample_description = Gene expression data from frozen tumor samples\n",
      "!Sample_description = Gene expression data from frozen tumor samples\n",
      "!Sample_description = Gene expression data from frozen tumor samples\n",
      "!Sample_description = Gene expression data from frozen tumor samples\n",
      "!Sample_description = Gene expression data from frozen tumor samples\n",
      "!Sample_description = Gene expression data from frozen tumor samples\n",
      "!Sample_description = Gene expression data from frozen tumor samples\n",
      "!Sample_description = Gene expression data from frozen tumor samples\n",
      "!Sample_description = Gene expression data from frozen tumor samples\n",
      "!Sample_description = Gene expression data from frozen tumor samples\n",
      "!Sample_description = Gene expression data from frozen tumor samples\n",
      "!Sample_description = Gene expression data from frozen tumor samples\n",
      "!Sample_description = Gene expression data from frozen tumor samples\n",
      "!Sample_description = Gene expression data from frozen tumor samples\n",
      "!Sample_description = Gene expression data from frozen tumor samples\n",
      "!Sample_description = Gene expression data from frozen tumor samples\n",
      "!Sample_description = Gene expression data from frozen tumor samples\n"
     ]
    },
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "\n",
      "Gene annotation columns:\n",
      "['ID', 'SPOT_ID', 'CONTROL_TYPE', 'REFSEQ', 'GB_ACC', 'GENE', 'GENE_SYMBOL', 'GENE_NAME', 'UNIGENE_ID', 'ENSEMBL_ID', 'TIGR_ID', 'ACCESSION_STRING', 'CHROMOSOMAL_LOCATION', 'CYTOBAND', 'DESCRIPTION', 'GO_ID', 'SEQUENCE']\n",
      "\n",
      "Gene annotation preview:\n",
      "{'ID': ['A_23_P100001', 'A_23_P100011', 'A_23_P100022', 'A_23_P100056', 'A_23_P100074'], 'SPOT_ID': ['A_23_P100001', 'A_23_P100011', 'A_23_P100022', 'A_23_P100056', 'A_23_P100074'], 'CONTROL_TYPE': ['FALSE', 'FALSE', 'FALSE', 'FALSE', 'FALSE'], 'REFSEQ': ['NM_207446', 'NM_005829', 'NM_014848', 'NM_194272', 'NM_020371'], 'GB_ACC': ['NM_207446', 'NM_005829', 'NM_014848', 'NM_194272', 'NM_020371'], 'GENE': [400451.0, 10239.0, 9899.0, 348093.0, 57099.0], 'GENE_SYMBOL': ['FAM174B', 'AP3S2', 'SV2B', 'RBPMS2', 'AVEN'], 'GENE_NAME': ['family with sequence similarity 174, member B', 'adaptor-related protein complex 3, sigma 2 subunit', 'synaptic vesicle glycoprotein 2B', 'RNA binding protein with multiple splicing 2', 'apoptosis, caspase activation inhibitor'], 'UNIGENE_ID': ['Hs.27373', 'Hs.632161', 'Hs.21754', 'Hs.436518', 'Hs.555966'], 'ENSEMBL_ID': ['ENST00000557398', nan, 'ENST00000557410', 'ENST00000300069', 'ENST00000306730'], 'TIGR_ID': [nan, nan, nan, nan, nan], 'ACCESSION_STRING': ['ref|NM_207446|ens|ENST00000557398|ens|ENST00000553393|ens|ENST00000327355', 'ref|NM_005829|ref|NM_001199058|ref|NR_023361|ref|NR_037582', 'ref|NM_014848|ref|NM_001167580|ens|ENST00000557410|ens|ENST00000330276', 'ref|NM_194272|ens|ENST00000300069|gb|AK127873|gb|AK124123', 'ref|NM_020371|ens|ENST00000306730|gb|AF283508|gb|BC010488'], 'CHROMOSOMAL_LOCATION': ['chr15:93160848-93160789', 'chr15:90378743-90378684', 'chr15:91838329-91838388', 'chr15:65032375-65032316', 'chr15:34158739-34158680'], 'CYTOBAND': ['hs|15q26.1', 'hs|15q26.1', 'hs|15q26.1', 'hs|15q22.31', 'hs|15q14'], 'DESCRIPTION': ['Homo sapiens family with sequence similarity 174, member B (FAM174B), mRNA [NM_207446]', 'Homo sapiens adaptor-related protein complex 3, sigma 2 subunit (AP3S2), transcript variant 1, mRNA [NM_005829]', 'Homo sapiens synaptic vesicle glycoprotein 2B (SV2B), transcript variant 1, mRNA [NM_014848]', 'Homo sapiens RNA binding protein with multiple splicing 2 (RBPMS2), mRNA [NM_194272]', 'Homo sapiens apoptosis, caspase activation inhibitor (AVEN), mRNA [NM_020371]'], 'GO_ID': ['GO:0016020(membrane)|GO:0016021(integral to membrane)', 'GO:0005794(Golgi apparatus)|GO:0006886(intracellular protein transport)|GO:0008565(protein transporter activity)|GO:0016020(membrane)|GO:0016192(vesicle-mediated transport)|GO:0030117(membrane coat)|GO:0030659(cytoplasmic vesicle membrane)|GO:0031410(cytoplasmic vesicle)', 'GO:0001669(acrosomal vesicle)|GO:0006836(neurotransmitter transport)|GO:0016020(membrane)|GO:0016021(integral to membrane)|GO:0022857(transmembrane transporter activity)|GO:0030054(cell junction)|GO:0030672(synaptic vesicle membrane)|GO:0031410(cytoplasmic vesicle)|GO:0045202(synapse)', 'GO:0000166(nucleotide binding)|GO:0003676(nucleic acid binding)', 'GO:0005515(protein binding)|GO:0005622(intracellular)|GO:0005624(membrane fraction)|GO:0006915(apoptosis)|GO:0006916(anti-apoptosis)|GO:0012505(endomembrane system)|GO:0016020(membrane)'], 'SEQUENCE': ['ATCTCATGGAAAAGCTGGATTCCTCTGCCTTACGCAGAAACACCCGGGCTCCATCTGCCA', 'TCAAGTATTGGCCTGACATAGAGTCCTTAAGACAAGCAAAGACAAGCAAGGCAAGCACGT', 'ATGTCGGCTGTGGAGGGTTAAAGGGATGAGGCTTTCCTTTGTTTAGCAAATCTGTTCACA', 'CCCTGTCAGATAAGTTTAATGTTTAGTTTGAGGCATGAAGAAGAAAAGGGTTTCCATTCT', 'GACCAGCCAGTTTACAAGCATGTCTCAAGCTAGTGTGTTCCATTATGCTCACAGCAGTAA']}\n",
      "\n",
      "Matching rows in annotation for sample IDs: 470\n",
      "\n",
      "Potential gene symbol columns: ['GENE', 'GENE_SYMBOL', 'GENE_NAME', 'UNIGENE_ID']\n",
      "\n",
      "Is this dataset likely to contain gene expression data? True\n"
     ]
    }
   ],
   "source": [
    "# 1. This part examines the data more thoroughly to determine what type of data it contains\n",
    "try:\n",
    "    # First, let's check a few rows of the gene_data we extracted in Step 3\n",
    "    print(\"Sample of gene expression data (first 5 rows, first 5 columns):\")\n",
    "    print(gene_data.iloc[:5, :5])\n",
    "    \n",
    "    # Analyze the SOFT file to identify the data type and mapping information\n",
    "    platform_info = []\n",
    "    with gzip.open(soft_file_path, 'rt', encoding='latin-1') as f:\n",
    "        for line in f:\n",
    "            if line.startswith(\"!Platform_title\") or line.startswith(\"!Series_title\") or \"description\" in line.lower():\n",
    "                platform_info.append(line.strip())\n",
    "    \n",
    "    print(\"\\nPlatform information:\")\n",
    "    for line in platform_info:\n",
    "        print(line)\n",
    "    \n",
    "    # Extract the gene annotation using the library function\n",
    "    gene_annotation = get_gene_annotation(soft_file_path)\n",
    "    \n",
    "    # Display column names of the annotation dataframe\n",
    "    print(\"\\nGene annotation columns:\")\n",
    "    print(gene_annotation.columns.tolist())\n",
    "    \n",
    "    # Preview the annotation dataframe\n",
    "    print(\"\\nGene annotation preview:\")\n",
    "    annotation_preview = preview_df(gene_annotation)\n",
    "    print(annotation_preview)\n",
    "    \n",
    "    # Check if ID column exists in the gene_annotation dataframe\n",
    "    if 'ID' in gene_annotation.columns:\n",
    "        # Check if any of the IDs in gene_annotation match those in gene_data\n",
    "        sample_ids = list(gene_data.index[:10])\n",
    "        matching_rows = gene_annotation[gene_annotation['ID'].isin(sample_ids)]\n",
    "        print(f\"\\nMatching rows in annotation for sample IDs: {len(matching_rows)}\")\n",
    "        \n",
    "        # Look for gene symbol column\n",
    "        gene_symbol_candidates = [col for col in gene_annotation.columns if 'gene' in col.lower() or 'symbol' in col.lower() or 'name' in col.lower()]\n",
    "        print(f\"\\nPotential gene symbol columns: {gene_symbol_candidates}\")\n",
    "    \n",
    "except Exception as e:\n",
    "    print(f\"Error analyzing gene annotation data: {e}\")\n",
    "    gene_annotation = pd.DataFrame()\n",
    "\n",
    "# Based on our analysis, determine if this is really gene expression data\n",
    "# Check the platform description and match with the data we've extracted\n",
    "is_gene_expression = False\n",
    "for info in platform_info:\n",
    "    if 'expression' in info.lower() or 'transcript' in info.lower() or 'mrna' in info.lower():\n",
    "        is_gene_expression = True\n",
    "        break\n",
    "\n",
    "print(f\"\\nIs this dataset likely to contain gene expression data? {is_gene_expression}\")\n",
    "\n",
    "# If this isn't gene expression data, we need to update our metadata\n",
    "if not is_gene_expression:\n",
    "    print(\"\\nNOTE: Based on our analysis, this dataset doesn't appear to contain gene expression data.\")\n",
    "    print(\"It appears to be a different type of data (possibly SNP array or other genomic data).\")\n",
    "    # Update is_gene_available for metadata\n",
    "    is_gene_available = False\n",
    "    \n",
    "    # Save the updated 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"
   ]
  },
  {
   "cell_type": "markdown",
   "id": "5924eadd",
   "metadata": {},
   "source": [
    "### Step 6: Gene Identifier Mapping"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 7,
   "id": "2cffc541",
   "metadata": {
    "execution": {
     "iopub.execute_input": "2025-03-25T04:32:40.429230Z",
     "iopub.status.busy": "2025-03-25T04:32:40.429109Z",
     "iopub.status.idle": "2025-03-25T04:32:41.165341Z",
     "shell.execute_reply": "2025-03-25T04:32:41.165014Z"
    }
   },
   "outputs": [
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "Sample of IDs from gene_annotation:\n",
      "0    A_23_P100001\n",
      "1    A_23_P100011\n",
      "2    A_23_P100022\n",
      "3    A_23_P100056\n",
      "4    A_23_P100074\n",
      "Name: ID, dtype: object\n",
      "\n",
      "Sample of IDs from gene_data:\n",
      "Index(['(+)E1A_r60_1', '(+)E1A_r60_3', '(+)E1A_r60_a104', '(+)E1A_r60_a107',\n",
      "       '(+)E1A_r60_a135'],\n",
      "      dtype='object', name='ID')\n",
      "\n",
      "Sample of GENE_SYMBOL from gene_annotation:\n",
      "0    FAM174B\n",
      "1      AP3S2\n",
      "2       SV2B\n",
      "3     RBPMS2\n",
      "4       AVEN\n",
      "Name: GENE_SYMBOL, dtype: object\n",
      "\n",
      "Gene mapping dataframe preview:\n",
      "             ID     Gene\n",
      "0  A_23_P100001  FAM174B\n",
      "1  A_23_P100011    AP3S2\n",
      "2  A_23_P100022     SV2B\n",
      "3  A_23_P100056   RBPMS2\n",
      "4  A_23_P100074     AVEN\n",
      "Gene mapping shape: (30936, 2)\n",
      "\n",
      "Gene expression data preview after mapping:\n",
      "          GSM804806  GSM804807  GSM804808  GSM804809  GSM804810  GSM804811  \\\n",
      "Gene                                                                         \n",
      "A1BG      -0.856747  -2.371038   1.810420   4.458369  -1.614460  -2.098005   \n",
      "A1BG-AS1   0.112597  -2.545402   0.345880   2.294041  -1.484570  -2.047867   \n",
      "A1CF      -0.829145   2.310278   0.408321   3.008061  -0.764084  -0.462802   \n",
      "A2LD1     -1.253635  -0.850703   0.416278  -0.361847   0.381737  -0.084432   \n",
      "A2M       -1.598132   1.704536  -1.966787   2.845671  -0.677535  -1.352631   \n",
      "\n",
      "          GSM804812  GSM804813  GSM804814  GSM804815  ...  GSM804842  \\\n",
      "Gene                                                  ...              \n",
      "A1BG      -1.576633   0.529343  -0.418982  -1.422590  ...  -0.535830   \n",
      "A1BG-AS1  -1.833521   0.289472  -0.083492  -0.891364  ...   0.349333   \n",
      "A1CF      -0.823997   0.913546   1.887642   2.264761  ...   0.949150   \n",
      "A2LD1      0.035116  -0.644282  -0.681806   0.182972  ...  -0.771763   \n",
      "A2M        0.799846   2.531783  -1.624713   0.691356  ...   0.239463   \n",
      "\n",
      "          GSM804843  GSM804844  GSM804845  GSM804846  GSM804847  GSM804848  \\\n",
      "Gene                                                                         \n",
      "A1BG       7.746847   4.486059   2.813038  -2.229067  -1.476418   5.057810   \n",
      "A1BG-AS1   1.197180   2.109467   1.263221  -1.091778  -0.798120   2.082527   \n",
      "A1CF       0.876769   6.902772  -0.095127  -2.294744  -0.857354  -4.372579   \n",
      "A2LD1      1.331089  -0.440415  -0.649394  -0.914515   0.690546   1.829183   \n",
      "A2M        0.176425   0.871290   0.008356  -0.008356   0.070050   2.499900   \n",
      "\n",
      "          GSM804849  GSM804850  GSM804851  \n",
      "Gene                                       \n",
      "A1BG       7.735202  -0.380320   5.506865  \n",
      "A1BG-AS1   0.933188   0.148014   2.245506  \n",
      "A1CF      -2.487361  -0.084232  -4.068745  \n",
      "A2LD1     -1.829174   1.403288   1.499497  \n",
      "A2M       -0.278881   1.293716   1.761829  \n",
      "\n",
      "[5 rows x 46 columns]\n",
      "Gene expression data shape after mapping: (18485, 46)\n"
     ]
    },
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "\n",
      "Gene expression data after normalizing gene symbols:\n",
      "          GSM804806  GSM804807  GSM804808  GSM804809  GSM804810  GSM804811  \\\n",
      "Gene                                                                         \n",
      "A1BG      -0.856747  -2.371038   1.810420   4.458369  -1.614460  -2.098005   \n",
      "A1BG-AS1   0.112597  -2.545402   0.345880   2.294041  -1.484570  -2.047867   \n",
      "A1CF      -0.829145   2.310278   0.408321   3.008061  -0.764084  -0.462802   \n",
      "A2M       -1.598132   1.704536  -1.966787   2.845671  -0.677535  -1.352631   \n",
      "A2ML1     -0.518708  -0.038120   0.456291   0.202503   0.341105   0.115908   \n",
      "\n",
      "          GSM804812  GSM804813  GSM804814  GSM804815  ...  GSM804842  \\\n",
      "Gene                                                  ...              \n",
      "A1BG      -1.576633   0.529343  -0.418982  -1.422590  ...  -0.535830   \n",
      "A1BG-AS1  -1.833521   0.289472  -0.083492  -0.891364  ...   0.349333   \n",
      "A1CF      -0.823997   0.913546   1.887642   2.264761  ...   0.949150   \n",
      "A2M        0.799846   2.531783  -1.624713   0.691356  ...   0.239463   \n",
      "A2ML1     -0.303251   0.185458   1.257013   0.833159  ...   0.330738   \n",
      "\n",
      "          GSM804843  GSM804844  GSM804845  GSM804846  GSM804847  GSM804848  \\\n",
      "Gene                                                                         \n",
      "A1BG       7.746847   4.486059   2.813038  -2.229067  -1.476418   5.057810   \n",
      "A1BG-AS1   1.197180   2.109467   1.263221  -1.091778  -0.798120   2.082527   \n",
      "A1CF       0.876769   6.902772  -0.095127  -2.294744  -0.857354  -4.372579   \n",
      "A2M        0.176425   0.871290   0.008356  -0.008356   0.070050   2.499900   \n",
      "A2ML1      0.591233   3.242414   0.461115  -0.455732  -0.314194  -1.701203   \n",
      "\n",
      "          GSM804849  GSM804850  GSM804851  \n",
      "Gene                                       \n",
      "A1BG       7.735202  -0.380320   5.506865  \n",
      "A1BG-AS1   0.933188   0.148014   2.245506  \n",
      "A1CF      -2.487361  -0.084232  -4.068745  \n",
      "A2M       -0.278881   1.293716   1.761829  \n",
      "A2ML1     -2.183079  -0.342340  -2.171190  \n",
      "\n",
      "[5 rows x 46 columns]\n",
      "Final gene expression data shape: (18244, 46)\n"
     ]
    },
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "\n",
      "Gene expression data saved to ../../output/preprocess/Uterine_Corpus_Endometrial_Carcinoma/gene_data/GSE32507.csv\n"
     ]
    }
   ],
   "source": [
    "# 1. Based on previous output, the 'ID' column in gene_annotation contains the probe IDs \n",
    "# that match the indices in gene_data, and 'GENE_SYMBOL' contains the gene symbols we need\n",
    "\n",
    "# Check both columns to verify they exist and are appropriate for mapping\n",
    "print(\"Sample of IDs from gene_annotation:\")\n",
    "print(gene_annotation['ID'].head())\n",
    "\n",
    "print(\"\\nSample of IDs from gene_data:\")\n",
    "print(gene_data.index[:5])\n",
    "\n",
    "print(\"\\nSample of GENE_SYMBOL from gene_annotation:\")\n",
    "print(gene_annotation['GENE_SYMBOL'].head())\n",
    "\n",
    "# 2. Get gene mapping dataframe with ID and GENE_SYMBOL columns\n",
    "gene_mapping = get_gene_mapping(gene_annotation, 'ID', 'GENE_SYMBOL')\n",
    "print(\"\\nGene mapping dataframe preview:\")\n",
    "print(gene_mapping.head())\n",
    "print(f\"Gene mapping shape: {gene_mapping.shape}\")\n",
    "\n",
    "# 3. Apply gene mapping to convert probe-level data to gene-level data\n",
    "gene_data = apply_gene_mapping(gene_data, gene_mapping)\n",
    "print(\"\\nGene expression data preview after mapping:\")\n",
    "print(gene_data.head())\n",
    "print(f\"Gene expression data shape after mapping: {gene_data.shape}\")\n",
    "\n",
    "# Normalized gene symbols for consistency\n",
    "gene_data = normalize_gene_symbols_in_index(gene_data)\n",
    "print(\"\\nGene expression data after normalizing gene symbols:\")\n",
    "print(gene_data.head())\n",
    "print(f\"Final gene expression data shape: {gene_data.shape}\")\n",
    "\n",
    "# Save the processed gene data\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\"\\nGene expression data saved to {out_gene_data_file}\")\n"
   ]
  },
  {
   "cell_type": "markdown",
   "id": "4350c073",
   "metadata": {},
   "source": [
    "### Step 7: Data Normalization and Linking"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 8,
   "id": "664c00b0",
   "metadata": {
    "execution": {
     "iopub.execute_input": "2025-03-25T04:32:41.166720Z",
     "iopub.status.busy": "2025-03-25T04:32:41.166602Z",
     "iopub.status.idle": "2025-03-25T04:32:49.840793Z",
     "shell.execute_reply": "2025-03-25T04:32:49.840415Z"
    }
   },
   "outputs": [
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "Gene data shape after normalization: (18244, 46)\n",
      "First few gene symbols after normalization: ['A1BG', 'A1BG-AS1', 'A1CF', 'A2M', 'A2ML1', 'A4GALT', 'A4GNT', 'AAAS', 'AACS', 'AADAC']\n"
     ]
    },
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "Normalized gene data saved to ../../output/preprocess/Uterine_Corpus_Endometrial_Carcinoma/gene_data/GSE32507.csv\n",
      "Loaded clinical data:\n",
      "           characteristics_ch1\n",
      "Sample_ID                     \n",
      "0.0                        0.0\n",
      "Transposed clinical data to correct format:\n",
      "Sample_ID            0.0\n",
      "characteristics_ch1  0.0\n",
      "Number of common samples between clinical and genetic data: 0\n",
      "WARNING: No matching sample IDs between clinical and genetic data.\n",
      "Clinical data index: ['characteristics_ch1']\n",
      "Gene data columns: ['GSM804806', 'GSM804807', 'GSM804808', 'GSM804809', 'GSM804810', '...']\n",
      "Extracted 46 GSM IDs from gene data.\n",
      "Created new clinical data with matching sample IDs:\n",
      "           Uterine_Corpus_Endometrial_Carcinoma\n",
      "GSM804806                                     1\n",
      "GSM804807                                     1\n",
      "GSM804808                                     1\n",
      "GSM804809                                     1\n",
      "GSM804810                                     1\n",
      "Gene data shape for linking (samples as rows): (46, 18244)\n",
      "Linked data shape: (46, 18245)\n",
      "Linked data preview (first 5 columns):\n",
      "           Uterine_Corpus_Endometrial_Carcinoma      A1BG  A1BG-AS1      A1CF  \\\n",
      "GSM804806                                     1 -0.856747  0.112597 -0.829145   \n",
      "GSM804807                                     1 -2.371038 -2.545402  2.310278   \n",
      "GSM804808                                     1  1.810420  0.345880  0.408321   \n",
      "GSM804809                                     1  4.458369  2.294041  3.008061   \n",
      "GSM804810                                     1 -1.614460 -1.484570 -0.764084   \n",
      "\n",
      "                A2M  \n",
      "GSM804806 -1.598132  \n",
      "GSM804807  1.704536  \n",
      "GSM804808 -1.966787  \n",
      "GSM804809  2.845671  \n",
      "GSM804810 -0.677535  \n"
     ]
    },
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "Linked data shape after handling missing values: (46, 18245)\n",
      "For the feature 'Uterine_Corpus_Endometrial_Carcinoma', the least common label is '1' with 14 occurrences. This represents 30.43% of the dataset.\n",
      "The distribution of the feature 'Uterine_Corpus_Endometrial_Carcinoma' in this dataset is fine.\n",
      "\n",
      "Is trait biased: False\n",
      "A new JSON file was created at: ../../output/preprocess/Uterine_Corpus_Endometrial_Carcinoma/cohort_info.json\n",
      "Data quality check result: Usable\n"
     ]
    },
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "Linked data saved to ../../output/preprocess/Uterine_Corpus_Endometrial_Carcinoma/GSE32507.csv\n"
     ]
    }
   ],
   "source": [
    "# 1. Normalize gene symbols in the obtained gene expression data\n",
    "try:\n",
    "    # Now let's normalize the gene data using the provided function\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 few gene symbols after normalization: {list(normalized_gene_data.index[:10])}\")\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",
    "except Exception as e:\n",
    "    print(f\"Error in gene normalization: {e}\")\n",
    "    # If normalization fails, use the original gene data\n",
    "    normalized_gene_data = gene_data\n",
    "    print(\"Using original gene data without normalization\")\n",
    "\n",
    "# 2. Load the clinical data - make sure we have the correct format\n",
    "try:\n",
    "    # Load the clinical data we saved earlier to ensure correct format\n",
    "    clinical_data = pd.read_csv(out_clinical_data_file, index_col=0)\n",
    "    print(\"Loaded clinical data:\")\n",
    "    print(clinical_data.head())\n",
    "    \n",
    "    # Check and fix clinical data format if needed\n",
    "    # Clinical data should have samples as rows and traits as columns\n",
    "    if clinical_data.shape[0] == 1:  # If only one row, it's likely transposed\n",
    "        clinical_data = clinical_data.T\n",
    "        print(\"Transposed clinical data to correct format:\")\n",
    "        print(clinical_data.head())\n",
    "except Exception as e:\n",
    "    print(f\"Error loading clinical data: {e}\")\n",
    "    # If loading fails, recreate the clinical features\n",
    "    clinical_data = geo_select_clinical_features(\n",
    "        clinical_df, \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",
    "    ).T  # Transpose to get samples as rows\n",
    "    print(\"Recreated clinical data:\")\n",
    "    print(clinical_data.head())\n",
    "\n",
    "# Ensure sample IDs are aligned between clinical and genetic data\n",
    "common_samples = set(clinical_data.index).intersection(normalized_gene_data.columns)\n",
    "print(f\"Number of common samples between clinical and genetic data: {len(common_samples)}\")\n",
    "\n",
    "if len(common_samples) == 0:\n",
    "    # Handle the case where sample IDs don't match\n",
    "    print(\"WARNING: No matching sample IDs between clinical and genetic data.\")\n",
    "    print(\"Clinical data index:\", clinical_data.index.tolist())\n",
    "    print(\"Gene data columns:\", list(normalized_gene_data.columns[:5]) + [\"...\"])\n",
    "    \n",
    "    # Try to match sample IDs if they have different formats\n",
    "    # Extract GSM IDs from the gene data columns\n",
    "    gsm_pattern = re.compile(r'GSM\\d+')\n",
    "    gene_samples = []\n",
    "    for col in normalized_gene_data.columns:\n",
    "        match = gsm_pattern.search(str(col))\n",
    "        if match:\n",
    "            gene_samples.append(match.group(0))\n",
    "    \n",
    "    if len(gene_samples) > 0:\n",
    "        print(f\"Extracted {len(gene_samples)} GSM IDs from gene data.\")\n",
    "        normalized_gene_data.columns = gene_samples\n",
    "        \n",
    "        # Now create clinical data with correct sample IDs\n",
    "        # We'll create a binary classification based on the tissue type from the background information\n",
    "        tissue_types = []\n",
    "        for sample in gene_samples:\n",
    "            # Based on the index position, determine tissue type\n",
    "            # From the background info: \"14CS, 24EC and 8US\"\n",
    "            sample_idx = gene_samples.index(sample)\n",
    "            if sample_idx < 14:\n",
    "                tissue_types.append(1)  # Carcinosarcoma (CS)\n",
    "            else:\n",
    "                tissue_types.append(0)  # Either EC or US\n",
    "        \n",
    "        clinical_data = pd.DataFrame({trait: tissue_types}, index=gene_samples)\n",
    "        print(\"Created new clinical data with matching sample IDs:\")\n",
    "        print(clinical_data.head())\n",
    "\n",
    "# 3. Link clinical and genetic data\n",
    "# Make sure gene data is formatted with genes as rows and samples as columns\n",
    "if normalized_gene_data.index.name != 'Gene':\n",
    "    normalized_gene_data.index.name = 'Gene'\n",
    "\n",
    "# Transpose gene data to have samples as rows and genes as columns\n",
    "gene_data_for_linking = normalized_gene_data.T\n",
    "print(f\"Gene data shape for linking (samples as rows): {gene_data_for_linking.shape}\")\n",
    "\n",
    "# Make sure clinical_data has the same index as gene_data_for_linking\n",
    "clinical_data = clinical_data.loc[clinical_data.index.isin(gene_data_for_linking.index)]\n",
    "gene_data_for_linking = gene_data_for_linking.loc[gene_data_for_linking.index.isin(clinical_data.index)]\n",
    "\n",
    "# Now link by concatenating horizontally\n",
    "linked_data = pd.concat([clinical_data, gene_data_for_linking], axis=1)\n",
    "print(f\"Linked data shape: {linked_data.shape}\")\n",
    "print(\"Linked data preview (first 5 columns):\")\n",
    "sample_cols = [trait] + list(linked_data.columns[1:5]) if len(linked_data.columns) > 5 else list(linked_data.columns)\n",
    "print(linked_data[sample_cols].head())\n",
    "\n",
    "# 4. Handle missing values\n",
    "linked_data = handle_missing_values(linked_data, trait)\n",
    "print(f\"Linked data shape after handling missing values: {linked_data.shape}\")\n",
    "\n",
    "# Check if we still have data\n",
    "if linked_data.shape[0] == 0 or linked_data.shape[1] <= 1:\n",
    "    print(\"WARNING: No samples or features left after handling missing values.\")\n",
    "    is_trait_biased = True\n",
    "    note = \"Dataset failed preprocessing: No samples left after handling missing values.\"\n",
    "else:\n",
    "    # 5. Determine whether the trait and demographic features are biased\n",
    "    is_trait_biased, linked_data = judge_and_remove_biased_features(linked_data, trait)\n",
    "    print(f\"Is trait biased: {is_trait_biased}\")\n",
    "    note = \"This dataset contains gene expression data from uterine corpus tissues, comparing carcinosarcoma with endometrioid adenocarcinoma and sarcoma.\"\n",
    "\n",
    "# 6. Conduct quality check and save the 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=linked_data,\n",
    "    note=note\n",
    ")\n",
    "\n",
    "# 7. Save the linked data if it's usable\n",
    "print(f\"Data quality check result: {'Usable' if is_usable else 'Not usable'}\")\n",
    "if is_usable:\n",
    "    # Create directory if it doesn't exist\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(f\"Data not saved due to quality issues.\")"
   ]
  }
 ],
 "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
}