File size: 4,821 Bytes
f07511a
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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
# -*- coding: utf-8 -*-
"""Untitled17.ipynb

Automatically generated by Colab.

Original file is located at
    https://colab.research.google.com/drive/1GwdSjrwh3f6QCzOa8KHr_XkWy0KmZvdV
"""

import pandas as pd
import numpy as np
from ast import literal_eval
import re

df_disprot = pd.read_parquet(PATHS['disprot'] / 'disprot_data.parquet')
df_uniprot = pd.read_parquet(PATHS['uniprot'] / 'uniprot_mitochondrial.parquet')
df_clinvar = pd.read_parquet(PATHS['clinvar'] / 'clinvar_variants.parquet')
df_mobidb = pd.read_parquet(PATHS['mobidb'] / 'mobidb_data.parquet')

print(f"    DisProt: {len(df_disprot)} ")
print(f"    UniProt: {len(df_uniprot)} ")
print(f"    ClinVar: {len(df_clinvar)} ")
print(f"    MobiDB: {len(df_mobidb)} ")


mito_accs = set(df_uniprot['uniprot_acc'].unique())

df_disprot_mito = df_disprot[df_disprot['uniprot_acc'].isin(mito_accs)].copy()
print(f"   ✓ DisProt : {len(df_disprot_mito)} régions ({df_disprot_mito['uniprot_acc'].nunique()} protéines)")

idp_mito_accs = set(df_disprot_mito['uniprot_acc'].unique())







def parse_protein_change(change_str: str) -> dict:
    if not change_str or pd.isna(change_str):
        return None


    aa_map = {
        'Ala': 'A', 'Arg': 'R', 'Asn': 'N', 'Asp': 'D', 'Cys': 'C',
        'Gln': 'Q', 'Glu': 'E', 'Gly': 'G', 'His': 'H', 'Ile': 'I',
        'Leu': 'L', 'Lys': 'K', 'Met': 'M', 'Phe': 'F', 'Pro': 'P',
        'Ser': 'S', 'Thr': 'T', 'Trp': 'W', 'Tyr': 'Y', 'Val': 'V',
        'Ter': '*'
    }

    pattern = r'([A-Z][a-z]{2})(\d+)([A-Z][a-z]{2})'
    match = re.match(pattern, change_str)

    if match:
        wt_3 = match.group(1)
        pos = int(match.group(2))
        mut_3 = match.group(3)

        wt_1 = aa_map.get(wt_3, '?')
        mut_1 = aa_map.get(mut_3, '?')

        if wt_1 != '?' and mut_1 != '?' and mut_1 != '*':
            return {
                'position': pos - 1,
                'wt_aa': wt_1,
                'mut_aa': mut_1
            }

    return None

parsed_mutations = []
for idx, row in df_clinvar.iterrows():
    parsed = parse_protein_change(row['protein_change'])
    if parsed:
        parsed['clinvar_id'] = row['clinvar_id']
        parsed['gene'] = row['gene']
        parsed['is_pathogenic'] = row['is_pathogenic']
        parsed['is_benign'] = row['is_benign']
        parsed['clinical_significance'] = row['clinical_significance']
        parsed_mutations.append(parsed)

df_mutations = pd.DataFrame(parsed_mutations)
print(f"   ✓ {len(df_mutations)} mutations parsées avec succès")

n_pathogenic = df_mutations['is_pathogenic'].sum()
n_benign = df_mutations['is_benign'].sum()
print(f"   ✓ Pathognes {n_pathogenic}")
print(f"   ✓ Bénin: {n_benign}")






gene_to_seq = {}
gene_to_acc = {}
for _, row in df_uniprot.iterrows():
    gene = row['gene_name']
    if gene and row['sequence']:
        gene_to_seq[gene] = row['sequence']
        gene_to_acc[gene] = row['uniprot_acc']

df_mutations['sequence'] = df_mutations['gene'].map(gene_to_seq)
df_mutations['uniprot_acc'] = df_mutations['gene'].map(gene_to_acc)

df_mutations_valid = df_mutations.dropna(subset=['sequence']).copy()

def validate_mutation(row):
    seq = row['sequence']
    pos = row['position']
    wt = row['wt_aa']

    if pos < 0 or pos >= len(seq):
        return False

    actual_aa = seq[pos]
    return actual_aa == wt

df_mutations_valid['is_valid'] = df_mutations_valid.apply(validate_mutation, axis=1)
df_mutations_final = df_mutations_valid[df_mutations_valid['is_valid']].copy()

print(f"   ✓ {len(df_mutations_final)} mutations validé")


df_pathogenic = df_mutations_final[df_mutations_final['is_pathogenic']].copy()
df_benign = df_mutations_final[df_mutations_final['is_benign']].copy()

print(f"   Pathogènes : {len(df_pathogenic)}")
print(f"   Bénins : {len(df_benign)}")

df_pathogenic['label'] = 1
df_benign['label'] = 0

df_dataset = pd.concat([df_pathogenic, df_benign], ignore_index=True)
df_dataset = df_dataset.sample(frac=1, random_state=42).reset_index(drop=True)

print(f"   ✓ : {len(df_dataset)} mutations")



disorder_regions_by_acc = {}
for acc in df_disprot['uniprot_acc'].unique():
    regions = df_disprot[df_disprot['uniprot_acc'] == acc][['region_start', 'region_end']].values.tolist()
    disorder_regions_by_acc[acc] = regions

def is_in_disorder_region(row):
    acc = row['uniprot_acc']
    pos = row['position'] + 1

    if acc not in disorder_regions_by_acc:
        return None
    for start, end in disorder_regions_by_acc[acc]:
        if start <= pos <= end:
            return True
    return False

df_dataset['in_disorder_region'] = df_dataset.apply(is_in_disorder_region, axis=1)

n_in_disorder = df_dataset['in_disorder_region'].sum()
n_annotated = df_dataset['in_disorder_region'].notna().sum()
print(f"   ✓ {n_in_disorder}/{n_annotated} ")