File size: 7,093 Bytes
f98d04c
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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
import torch
import torch.nn as nn
from transformers import PreTrainedModel, PretrainedConfig

from peft import LoraConfig, get_peft_model, TaskType
from transformers import EsmModel

class TransHLA2Config(PretrainedConfig):
    model_type = "transhla2"
    def __init__(self, d_model=480, **kwargs):
        super().__init__(**kwargs)
        self.d_model = d_model
        # 可加入其它自定义参数

class LoraESM(nn.Module):
    def __init__(self, d_model=480):
        super().__init__()
        self.model_name_or_path = "facebook/esm2_t12_35M_UR50D"
        self.tokenizer_name_or_path = "facebook/esm2_t12_35M_UR50D"
        self.peft_config = LoraConfig(
            target_modules=['query', 'out_proj', 'value', 'key', 'dense', 'regression'],
            task_type=TaskType.FEATURE_EXTRACTION, 
            inference_mode=False, r=8, lora_alpha=32, lora_dropout=0.1
        )
        self.esm = EsmModel.from_pretrained(self.model_name_or_path)
        self.lora_esm = get_peft_model(self.esm, self.peft_config)
        self.fc_task = nn.Sequential(
            nn.Linear(d_model, d_model // 4),
            nn.BatchNorm1d(d_model // 4),
            nn.Dropout(0.2),
            nn.SiLU(),
            nn.Linear(d_model // 4, 32),
            nn.BatchNorm1d(32),
        )
        self.classifier = nn.Linear(32, 2)

    def forward(self, x_in):
        lora_outputs = self.lora_esm(x_in)
        last_hidden_state = lora_outputs.last_hidden_state
        out_linear = last_hidden_state.mean(dim=1)
        H = self.fc_task(out_linear)
        output = self.classifier(H)
        return output, last_hidden_state
lora_esm = LoraESM()
class TransHLA2(PreTrainedModel):
    config_class = TransHLA2Config

    def __init__(self, config):
        super().__init__(config)
        n_layers = 4
        n_head = 8
        d_model = config.d_model
        d_ff = 64
        cnn_num_channel = 256
        region_embedding_size = 3
        cnn_kernel_size = 3
        cnn_padding_size = 1
        cnn_stride = 1
        pooling_size = 2

        self.lora_esm = lora_esm

        self.region_cnn1 = nn.Conv1d(d_model, cnn_num_channel, region_embedding_size)
        self.region_cnn2 = nn.Conv1d(d_model, cnn_num_channel, region_embedding_size)
        self.padding1 = nn.ConstantPad1d((1, 1), 0)
        self.padding2 = nn.ConstantPad1d((0, 1), 0)
        self.relu = nn.SiLU()
        self.cnn1 = nn.Conv1d(cnn_num_channel, cnn_num_channel, kernel_size=cnn_kernel_size,
                              padding=cnn_padding_size, stride=cnn_stride)
        self.cnn2 = nn.Conv1d(cnn_num_channel, cnn_num_channel, kernel_size=cnn_kernel_size,
                              padding=cnn_padding_size, stride=cnn_stride)
        self.maxpooling = nn.MaxPool1d(kernel_size=pooling_size)
        self.epitope_transformer_layers = nn.TransformerEncoderLayer(
            d_model=d_model, nhead=n_head, dim_feedforward=d_ff, dropout=0.2)
        self.epitope_transformer_encoder = nn.TransformerEncoder(
            self.epitope_transformer_layers, num_layers=n_layers)
        self.hla_transformer_layers = nn.TransformerEncoderLayer(
            d_model=d_model, nhead=n_head, dim_feedforward=d_ff, dropout=0.2)
        self.hla_transformer_encoder = nn.TransformerEncoder(
            self.hla_transformer_layers, num_layers=n_layers)
        
        # Cross Attention layers
        self.cross_attention_epitope_layers = nn.ModuleList(
            [nn.MultiheadAttention(d_model, n_head, dropout=0.2) for _ in range(4)])
        self.cross_attention_hla_layers = nn.ModuleList(
            [nn.MultiheadAttention(d_model, n_head, dropout=0.2) for _ in range(4)])

        self.bn1 = nn.BatchNorm1d(cnn_num_channel)
        self.bn2 = nn.BatchNorm1d(cnn_num_channel)
        self.fc_task = nn.Sequential(
            nn.Linear(2*d_model + 2*cnn_num_channel, 2 * (d_model + cnn_num_channel) // 4),
            nn.BatchNorm1d(2 * (d_model + cnn_num_channel) // 4),
            nn.Dropout(0.2),
            nn.SiLU(),
            nn.Linear(2 * (d_model + cnn_num_channel) // 4, 96),
            nn.BatchNorm1d(96),
        )
        self.classifier = nn.Linear(96, 2)

    def cnn_block1(self, x):
        return self.cnn1(self.relu(x))

    def cnn_block2(self, x):
        x = self.padding2(x)
        px = self.maxpooling(x)
        x = self.relu(px)
        x = self.cnn1(x)
        x = self.relu(x)
        x = self.cnn1(x)
        x = px + x
        return x

    def structure_block1(self, x):
        return self.cnn2(self.relu(x))

    def structure_block2(self, x):
        x = self.padding2(x)
        px = self.maxpooling(x)
        x = self.relu(px)
        x = self.cnn2(x)
        x = self.relu(x)
        x = self.cnn2(x)
        x = px + x
        return x

    def forward(self, epitope_in, hla_in):
        _, epitope_emb = self.lora_esm(epitope_in)
        _, hla_emb = self.lora_esm(hla_in)

        epitope_trans = self.epitope_transformer_encoder(epitope_emb.transpose(0, 1))
        hla_trans = self.hla_transformer_encoder(hla_emb.transpose(0, 1))

        # Cross Attention layers
        for cross_attention_epitope, cross_attention_hla in zip(self.cross_attention_epitope_layers, self.cross_attention_hla_layers):
            epitope_trans, _ = cross_attention_epitope(epitope_trans, hla_trans, hla_trans)
            hla_trans, _ = cross_attention_hla(hla_trans, epitope_trans, epitope_trans)

        # Mean Pooling
        epitope_mean = epitope_trans.mean(dim=0)
        hla_mean = hla_trans.mean(dim=0)
        
        epitope_cnn_emb = self.region_cnn1(epitope_emb.transpose(1, 2))
        epitope_cnn_emb = self.padding1(epitope_cnn_emb)
        conv = epitope_cnn_emb + self.cnn_block1(self.cnn_block1(epitope_cnn_emb))
        while conv.size(-1) >= 2:
            conv = self.cnn_block2(conv)
        epitope_cnn_out = torch.squeeze(conv, dim=-1)
        epitope_cnn_out = self.bn1(epitope_cnn_out)

        hla_cnn_emb = self.region_cnn2(hla_emb.transpose(1, 2))
        hla_cnn_emb = self.padding1(hla_cnn_emb)
        hla_conv = hla_cnn_emb + self.structure_block1(self.structure_block1(hla_cnn_emb))
        while hla_conv.size(-1) >= 2:
            hla_conv = self.structure_block2(hla_conv)

        hla_cnn_out = torch.squeeze(hla_conv, dim=-1)
        hla_cnn_out = self.bn2(hla_cnn_out)

        representation = torch.cat((epitope_mean, hla_mean, epitope_cnn_out, hla_cnn_out), dim=1)
        reduction_feature = self.fc_task(representation)
        logits_clsf = self.classifier(reduction_feature)
        logits_clsf = torch.nn.functional.softmax(logits_clsf, dim=1)
        return logits_clsf, reduction_feature


# config = TransHLA2Config(d_model=480)
# model = TransHLA2(config)

# model.load_state_dict(torch.load('pytorch_model.pt'))
# # 2. 保存为 transformers 兼容格式
# model.save_pretrained('pytorch_model.bin', safe_serialization=False)
# from transformers import AutoConfig, AutoModel, CONFIG_MAPPING, MODEL_MAPPING

# CONFIG_MAPPING.register("transhla2", TransHLA2Config)
# MODEL_MAPPING.register(TransHLA2Config, TransHLA2)