File size: 8,911 Bytes
c0ec7e6
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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
from math import floor
import re
from typing import Literal

import numpy as np
import torch.nn as nn
import torch
import torch.nn.functional as F


def conv(in_channels, out_channels, kernel_size, conv_dim, stride=1):
    conv_layer = None
    match conv_dim:
        case 1:
            conv_layer = nn.Conv1d
        case 2:
            conv_layer = nn.Conv2d
        case 3:
            conv_layer = nn.Conv3d
    return conv_layer(in_channels, out_channels,
                      kernel_size=kernel_size, stride=stride, padding=floor(kernel_size / 2), bias=False)


def batch_norm(out_channels, conv_dim):
    bn_layer = None
    match conv_dim:
        case 1:
            bn_layer = nn.BatchNorm1d
        case 2:
            bn_layer = nn.BatchNorm2d
        case 3:
            bn_layer = nn.BatchNorm3d
    return bn_layer(out_channels)


def conv3x3(in_channels, out_channels, stride=1):
    return nn.Conv2d(in_channels, out_channels, kernel_size=3,
                     stride=stride, padding=1, bias=False)


def conv5x5(in_channels, out_channels, stride=1):
    return nn.Conv2d(in_channels, out_channels, kernel_size=5,
                     stride=stride, padding=2, bias=False)


def conv1x1(in_channels, out_channels, stride=1):
    return nn.Conv2d(in_channels, out_channels, kernel_size=1,
                     stride=stride, padding=0, bias=False)


# Residual block
class ResidualBlock(nn.Module):
    def __init__(self, in_channels, out_channels, conv_dim, stride=1, downsample=None):
        super().__init__()
        # self.conv1 = conv5x5(in_channels, out_channels, stride)
        self.conv1 = conv(in_channels, out_channels, kernel_size=5, conv_dim=conv_dim, stride=stride)
        self.bn1 = batch_norm(out_channels, conv_dim=conv_dim)
        self.elu = nn.ELU(inplace=True)
        # self.conv2 = conv3x3(out_channels, out_channels)
        self.conv2 = conv(out_channels, out_channels, kernel_size=3, conv_dim=conv_dim, stride=stride)
        self.bn2 = batch_norm(out_channels, conv_dim=conv_dim)
        self.downsample = downsample

    def forward(self, x):
        residual = x
        out = self.conv1(x)
        out = self.bn1(out)
        out = self.elu(out)
        out = self.conv2(out)
        out = self.bn2(out)
        if self.downsample:
            residual = self.downsample(x)
        out += residual
        out = self.elu(out)
        return out


class DrugVQA(nn.Module):
    """
    The class is an implementation of the DrugVQA model including regularization and without pruning.
    Slight modifications have been done for speedup
    """

    def __init__(
            self,
            conv_dim: Literal[1, 2, 3],
            lstm_hid_dim: int,
            d_a: int,
            r: int,
            n_chars_smi: int,
            n_chars_seq: int,
            dropout: float,
            in_channels: int,
            cnn_channels: int,
            cnn_layers: int,
            emb_dim: int,
            dense_hid: int,
    ):
        """
        lstm_hid_dim: {int} hidden dimension for lstm
        d_a         : {int} hidden dimension for the dense layer
        r           : {int} attention-hops or attention heads
        n_chars_smi : {int} voc size of smiles
        n_chars_seq : {int} voc size of protein sequence
        dropout     : {float}
        in_channels : {int} channels of CNN block input
        cnn_channels: {int} channels of CNN block
        cnn_layers  : {int} num of layers of each CNN block
        emb_dim     : {int} embeddings dimension
        dense_hid   : {int} hidden dim for the output dense
        """
        super().__init__()
        self.conv_dim = conv_dim
        self.lstm_hid_dim = lstm_hid_dim
        self.r = r
        self.in_channels = in_channels
        # rnn
        self.embeddings = nn.Embedding(n_chars_smi, emb_dim)
        # self.seq_embed = nn.Embedding(n_chars_seq, emb_dim)
        self.lstm = nn.LSTM(emb_dim, self.lstm_hid_dim, 2, batch_first=True, bidirectional=True,
                            dropout=dropout)
        self.linear_first = nn.Linear(2 * self.lstm_hid_dim, d_a)
        self.linear_second = nn.Linear(d_a, r)
        self.linear_first_seq = nn.Linear(cnn_channels, d_a)
        self.linear_second_seq = nn.Linear(d_a, self.r)

        # cnn
        # self.conv = conv3x3(1, self.in_channels)
        self.conv = conv(1, self.in_channels, kernel_size=3, conv_dim=conv_dim)
        self.bn = batch_norm(in_channels, conv_dim=conv_dim)
        self.elu = nn.ELU(inplace=False)
        self.layer1 = self.make_layer(cnn_channels, cnn_layers)
        self.layer2 = self.make_layer(cnn_channels, cnn_layers)

        self.linear_final_step = nn.Linear(self.lstm_hid_dim * 2 + d_a, dense_hid)
        # self.linear_final = nn.Linear(dense_hid, n_classes)
        self.softmax = nn.Softmax(dim=1)

    # @staticmethod
    # def softmax(input, axis=1):
    #     """
    #     Softmax applied to axis=n
    #     Args:
    #        input: {Tensor,Variable} input on which softmax is to be applied
    #        axis : {int} axis on which softmax is to be applied
    #
    #     Returns:
    #         softmaxed tensors
    #     """
    #     input_size = input.size()
    #     trans_input = input.transpose(axis, len(input_size) - 1)
    #     trans_size = trans_input.size()
    #     input_2d = trans_input.contiguous().view(-1, trans_size[-1])
    #     soft_max_2d = F.softmax(input_2d)
    #     soft_max_nd = soft_max_2d.view(*trans_size)
    #     return soft_max_nd.transpose(axis, len(input_size) - 1)

    def make_layer(self, out_channels, blocks, stride=1):
        downsample = None
        if (stride != 1) or (self.in_channels != out_channels):
            downsample = nn.Sequential(
                # conv3x3(self.in_channels, out_channels, stride=stride),
                conv(self.in_channels, out_channels, kernel_size=3, conv_dim=self.conv_dim, stride=stride),
                batch_norm(out_channels, conv_dim=self.conv_dim)
            )
        layers = [ResidualBlock(self.in_channels, out_channels,
                                conv_dim=self.conv_dim, stride=stride, downsample=downsample)]
        self.in_channels = out_channels
        for i in range(1, blocks):
            layers.append(ResidualBlock(out_channels, out_channels, conv_dim=self.conv_dim))
        return nn.Sequential(*layers)

    def forward(self, enc_drug, enc_protein):
        enc_drug, _ = enc_drug
        enc_protein, _ = enc_protein
        smile_embed = self.embeddings(enc_drug.long())
        # self.hidden_state = tuple(hidden_state.to(smile_embed).detach() for hidden_state in self.hidden_state)
        outputs, hidden_state = self.lstm(smile_embed)
        sentence_att = F.tanh(self.linear_first(outputs))
        sentence_att = self.linear_second(sentence_att)
        sentence_att = self.softmax(sentence_att)
        sentence_att = sentence_att.transpose(1, 2)
        sentence_embed = sentence_att @ outputs
        avg_sentence_embed = torch.sum(sentence_embed, 1) / self.r  # multi head

        pic = self.conv(enc_protein.float().unsqueeze(1))
        pic = self.bn(pic)
        pic = self.elu(pic)
        pic = self.layer1(pic)
        pic = self.layer2(pic)
        pic_emb = torch.mean(pic, 2).unsqueeze(2)
        pic_emb = pic_emb.permute(0, 2, 1)
        seq_att = F.tanh(self.linear_first_seq(pic_emb))
        seq_att = self.linear_second_seq(seq_att)
        seq_att = self.softmax(seq_att)
        seq_att = seq_att.transpose(1, 2)
        seq_embed = seq_att @ pic_emb
        avg_seq_embed = torch.sum(seq_embed, 1) / self.r

        sscomplex = torch.cat([avg_sentence_embed, avg_seq_embed], dim=1)
        sscomplex = F.relu(self.linear_final_step(sscomplex))

        # if not bool(self.type):
        #     output = F.sigmoid(self.linear_final(sscomplex))
        #     return output, seq_att
        # else:
        #     return F.log_softmax(self.linear_final(sscomplex)), seq_att

        return sscomplex, seq_att


class AttentionL2Regularization(nn.Module):
    def __init__(self):
        super().__init__()

    def forward(self, seq_att):
        batch_size = seq_att.size(0)
        identity = torch.eye(seq_att.size(1), device=seq_att.device)
        identity = identity.unsqueeze(0).expand(batch_size, seq_att.size(1), seq_att.size(1))
        loss = torch.mean(self.l2_matrix_norm(seq_att @ seq_att.transpose(1, 2) - identity))
        return loss

    @staticmethod
    def l2_matrix_norm(m):
        """
        m = ||A * A_T - I||
        Missing from the original DrugVQA GitHub source code.
        Opting to use the faster Frobenius norm rather than the induced L2 matrix norm (spectral norm)
        proposed in the original research, because the goal is to minimize the difference between
        the attention matrix and the identity matrix.
        """
        return torch.linalg.norm(m, ord='fro', dim=(1, 2))