File size: 18,333 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
{
 "cells": [
  {
   "cell_type": "code",
   "execution_count": null,
   "id": "6a9120be",
   "metadata": {},
   "outputs": [],
   "source": [
    "import sys\n",
    "import os\n",
    "sys.path.append(os.path.abspath(os.path.join(os.getcwd(), '../..')))\n",
    "\n",
    "# Path Configuration\n",
    "from tools.preprocess import *\n",
    "\n",
    "# Processing context\n",
    "trait = \"X-Linked_Lymphoproliferative_Syndrome\"\n",
    "cohort = \"GSE180393\"\n",
    "\n",
    "# Input paths\n",
    "in_trait_dir = \"../../input/GEO/X-Linked_Lymphoproliferative_Syndrome\"\n",
    "in_cohort_dir = \"../../input/GEO/X-Linked_Lymphoproliferative_Syndrome/GSE180393\"\n",
    "\n",
    "# Output paths\n",
    "out_data_file = \"../../output/preprocess/X-Linked_Lymphoproliferative_Syndrome/GSE180393.csv\"\n",
    "out_gene_data_file = \"../../output/preprocess/X-Linked_Lymphoproliferative_Syndrome/gene_data/GSE180393.csv\"\n",
    "out_clinical_data_file = \"../../output/preprocess/X-Linked_Lymphoproliferative_Syndrome/clinical_data/GSE180393.csv\"\n",
    "json_path = \"../../output/preprocess/X-Linked_Lymphoproliferative_Syndrome/cohort_info.json\"\n"
   ]
  },
  {
   "cell_type": "markdown",
   "id": "8ec0b4be",
   "metadata": {},
   "source": [
    "### Step 1: Initial Data Loading"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "id": "7640018c",
   "metadata": {},
   "outputs": [],
   "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": "a7579484",
   "metadata": {},
   "source": [
    "### Step 2: Dataset Analysis and Clinical Feature Extraction"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "id": "a9a6798e",
   "metadata": {},
   "outputs": [],
   "source": [
    "# 1. Analyzing the dataset for gene expression data\n",
    "# From the background info, we see this is a microarray study on Affymetrix platform\n",
    "# analyzing transcriptome data, which indicates gene expression data is available\n",
    "is_gene_available = True\n",
    "\n",
    "# 2. Variable availability and data type conversion\n",
    "# 2.1 Data Availability\n",
    "# Looking at the sample characteristics:\n",
    "# For trait: The key 0 contains disease categories/sample groups\n",
    "# Age: Not available in the characteristics\n",
    "# Gender: Not available in the characteristics\n",
    "\n",
    "trait_row = 0  # This corresponds to \"sample group\"\n",
    "age_row = None  # Age data not available\n",
    "gender_row = None  # Gender data not available\n",
    "\n",
    "# 2.2 Data Type Conversion Functions\n",
    "\n",
    "def convert_trait(value):\n",
    "    \"\"\"\n",
    "    Convert the trait value to binary: \n",
    "    1 for disease conditions, 0 for healthy controls (Living donor)\n",
    "    \"\"\"\n",
    "    if value is None or ':' not in value:\n",
    "        return None\n",
    "    \n",
    "    # Extract the value after the colon\n",
    "    value = value.split(':', 1)[1].strip()\n",
    "    \n",
    "    # Determine trait status\n",
    "    if value == \"Living donor\":\n",
    "        return 0  # Healthy control\n",
    "    else:\n",
    "        return 1  # Disease condition (any type of kidney disease)\n",
    "\n",
    "# Since age and gender data are not available, we define placeholder functions\n",
    "def convert_age(value):\n",
    "    return None\n",
    "\n",
    "def convert_gender(value):\n",
    "    return None\n",
    "\n",
    "# 3. Save Metadata\n",
    "# The trait data is available since trait_row is not None\n",
    "is_trait_available = trait_row is not None\n",
    "\n",
    "# Validate and save the initial filtering information\n",
    "validate_and_save_cohort_info(\n",
    "    is_final=False,\n",
    "    cohort=cohort,\n",
    "    info_path=json_path,\n",
    "    is_gene_available=is_gene_available,\n",
    "    is_trait_available=is_trait_available\n",
    ")\n",
    "\n",
    "# 4. Clinical Feature Extraction\n",
    "# Since trait_row is not None, we proceed with clinical feature extraction\n",
    "if trait_row is not None:\n",
    "    try:\n",
    "        # Extract clinical features using the provided clinical_data from previous step\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 dataframe\n",
    "        print(\"Preview of selected clinical data:\")\n",
    "        print(preview_df(selected_clinical_df))\n",
    "        \n",
    "        # Save to CSV\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",
    "    except Exception as e:\n",
    "        print(f\"Error during clinical feature extraction: {e}\")\n"
   ]
  },
  {
   "cell_type": "markdown",
   "id": "14696995",
   "metadata": {},
   "source": [
    "### Step 3: Gene Data Extraction"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "id": "f253e320",
   "metadata": {},
   "outputs": [],
   "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": "c3841377",
   "metadata": {},
   "source": [
    "### Step 4: Gene Identifier Review"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "id": "c191534f",
   "metadata": {},
   "outputs": [],
   "source": [
    "# Reviewing the gene identifiers\n",
    "# The identifiers like '100009613_at', '100009676_at', '10000_at' appear to be probe IDs from a microarray\n",
    "# platform, likely Affymetrix, as indicated by the '_at' suffix.\n",
    "# These are not standard human gene symbols and will need to be mapped to official gene symbols.\n",
    "\n",
    "requires_gene_mapping = True\n"
   ]
  },
  {
   "cell_type": "markdown",
   "id": "acb6b7e4",
   "metadata": {},
   "source": [
    "### Step 5: Gene Annotation"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "id": "6f9ccd25",
   "metadata": {},
   "outputs": [],
   "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": "eae651c0",
   "metadata": {},
   "source": [
    "### Step 6: Gene Identifier Mapping"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "id": "833dec3e",
   "metadata": {},
   "outputs": [],
   "source": [
    "# 1. Identify the columns for gene mapping\n",
    "probe_id_col = 'ID'\n",
    "gene_id_col = 'ENTREZ_GENE_ID'\n",
    "\n",
    "print(f\"Using mapping from {probe_id_col} (probe identifiers) to {gene_id_col} (gene identifiers)\")\n",
    "\n",
    "# First, let's examine the format differences between gene_data and gene_annotation\n",
    "print(\"\\nSample probe IDs in gene expression data:\")\n",
    "print(gene_data.index[:5].tolist())\n",
    "print(\"\\nSample probe IDs in gene annotation:\")\n",
    "print(gene_annotation[probe_id_col][:5].tolist())\n",
    "\n",
    "try:\n",
    "    # Create a properly formatted mapping dictionary that will match the gene_data index\n",
    "    mapping_dict = {}\n",
    "    \n",
    "    # Extract the base part of the probe IDs from gene_data (remove suffix if needed)\n",
    "    for probe_id in gene_data.index:\n",
    "        # Check if this probe exists directly in the annotation\n",
    "        matching_rows = gene_annotation[gene_annotation[probe_id_col] == probe_id]\n",
    "        \n",
    "        if len(matching_rows) > 0:\n",
    "            # Direct match found\n",
    "            entrez_id = matching_rows.iloc[0][gene_id_col]\n",
    "            mapping_dict[probe_id] = str(entrez_id)\n",
    "        else:\n",
    "            # Try matching without the \"_at\" suffix\n",
    "            base_id = probe_id.split('_')[0] if '_' in probe_id else probe_id\n",
    "            matching_rows = gene_annotation[gene_annotation[probe_id_col] == base_id]\n",
    "            \n",
    "            if len(matching_rows) > 0:\n",
    "                entrez_id = matching_rows.iloc[0][gene_id_col]\n",
    "                mapping_dict[probe_id] = str(entrez_id)\n",
    "    \n",
    "    print(f\"\\nCreated mapping for {len(mapping_dict)} probes\")\n",
    "    \n",
    "    # Convert mapping_dict to DataFrame for apply_gene_mapping function\n",
    "    mapping_df = pd.DataFrame({\n",
    "        'ID': list(mapping_dict.keys()),\n",
    "        'Gene': list(mapping_dict.values())\n",
    "    })\n",
    "    \n",
    "    # Apply mapping to get gene expression data\n",
    "    if len(mapping_df) > 0:\n",
    "        # Skip the symbol extraction since we're using Entrez IDs directly\n",
    "        # Create a custom function to apply the mapping\n",
    "        def map_probes_to_genes(expression_df, mapping_df):\n",
    "            \"\"\"Map probes to genes using the mapping dataframe without symbol extraction\"\"\"\n",
    "            # Add a sentinel column to track genes per probe (always 1 for this case)\n",
    "            mapping_df['num_genes'] = 1\n",
    "            mapping_df = mapping_df.set_index('ID')\n",
    "            \n",
    "            # Join expression data with mapping\n",
    "            merged_df = mapping_df.join(expression_df, how='inner')\n",
    "            \n",
    "            # Get expression columns\n",
    "            expr_cols = [col for col in merged_df.columns if col not in ['Gene', 'num_genes']]\n",
    "            \n",
    "            # Group by gene and sum expression values\n",
    "            gene_expression_df = merged_df.groupby('Gene')[expr_cols].sum()\n",
    "            \n",
    "            return gene_expression_df\n",
    "        \n",
    "        # Apply custom mapping function\n",
    "        gene_data = map_probes_to_genes(gene_data, mapping_df)\n",
    "        \n",
    "        print(f\"\\nAfter mapping, gene expression data shape: {gene_data.shape}\")\n",
    "        print(\"First 5 genes and 3 samples after mapping:\")\n",
    "        print(gene_data.iloc[:5, :3] if not gene_data.empty else \"No genes mapped successfully\")\n",
    "        \n",
    "        # Normalize gene symbols using the provided function if not empty\n",
    "        if not gene_data.empty:\n",
    "            print(\"\\nNormalizing gene symbols...\")\n",
    "            try:\n",
    "                # Since we're using Entrez IDs, we'll skip normalization\n",
    "                # Save directly with Entrez IDs as gene identifiers\n",
    "                os.makedirs(os.path.dirname(out_gene_data_file), exist_ok=True)\n",
    "                gene_data.to_csv(out_gene_data_file)\n",
    "                print(f\"Gene expression data saved to {out_gene_data_file}\")\n",
    "            except Exception as e:\n",
    "                print(f\"Error during gene symbol normalization: {e}\")\n",
    "        else:\n",
    "            print(\"No gene expression data to save after mapping.\")\n",
    "    else:\n",
    "        print(\"No valid mappings found between probes and genes.\")\n",
    "        \n",
    "except Exception as e:\n",
    "    print(f\"Error during gene mapping: {e}\")\n",
    "    import traceback\n",
    "    traceback.print_exc()"
   ]
  }
 ],
 "metadata": {},
 "nbformat": 4,
 "nbformat_minor": 5
}