SMILES enumeration is the process of writing out all possible SMILES forms of a molecule. It's a useful technique for data augmentation before sequence based modeling of molecules. You can read more about the background in this blog post or this preprint on arxiv.org
Import the SmilesEnumerator and instantiate the object
from SmilesEnumerator import SmilesEnumerator
sme = SmilesEnumerator()
print(help(SmilesEnumerator))Help on class SmilesEnumerator in module SmilesEnumerator:
class SmilesEnumerator(builtins.object)
| SmilesEnumerator(charset='@C)(=cOn1S2/H[N]\\', pad=120, leftpad=True, isomericSmiles=True, enum=True, canonical=False)
|
| SMILES Enumerator, vectorizer and devectorizer
|
| #Arguments
| charset: string containing the characters for the vectorization
| can also be generated via the .fit() method
| pad: Length of the vectorization
| leftpad: Add spaces to the left of the SMILES
| isomericSmiles: Generate SMILES containing information about stereogenic centers
| enum: Enumerate the SMILES during transform
| canonical: use canonical SMILES during transform (overrides enum)
|
| Methods defined here:
|
| __init__(self, charset='@C)(=cOn1S2/H[N]\\', pad=120, leftpad=True, isomericSmiles=True, enum=True, canonical=False)
| Initialize self. See help(type(self)) for accurate signature.
|
| fit(self, smiles, extra_chars=[], extra_pad=5)
| Performs extraction of the charset and length of a SMILES datasets and sets self.pad and self.charset
|
| #Arguments
| smiles: Numpy array or Pandas series containing smiles as strings
| extra_chars: List of extra chars to add to the charset (e.g. "\\" when "/" is present)
| extra_pad: Extra padding to add before or after the SMILES vectorization
|
| randomize_smiles(self, smiles)
| Perform a randomization of a SMILES string
| must be RDKit sanitizable
|
| reverse_transform(self, vect)
| Performs a conversion of a vectorized SMILES to a smiles strings
| charset must be the same as used for vectorization.
| #Arguments
| vect: Numpy array of vectorized SMILES.
|
| transform(self, smiles)
| Perform an enumeration (randomization) and vectorization of a Numpy array of smiles strings
| #Arguments
| smiles: Numpy array or Pandas series containing smiles as strings
|
| ----------------------------------------------------------------------
| Data descriptors defined here:
|
| __dict__
| dictionary for instance variables (if defined)
|
| __weakref__
| list of weak references to the object (if defined)
|
| charset
None
A few SMILES strings will be enumerated as a demonstration.
for i in range(10):
print(sme.randomize_smiles("CCC(=O)O[C@@]1(CC[NH+](C[C@H]1CC=C)C)c2ccccc2"))c1cccc([C@@]2(OC(CC)=O)CC[NH+](C)C[C@H]2CC=C)c1
C([C@H]1[C@@](OC(CC)=O)(c2ccccc2)CC[NH+](C)C1)C=C
c1ccc([C@]2(OC(=O)CC)[C@H](CC=C)C[NH+](C)CC2)cc1
c1cccc([C@@]2(OC(=O)CC)CC[NH+](C)C[C@H]2CC=C)c1
C(=O)(CC)O[C@]1(c2ccccc2)CC[NH+](C)C[C@H]1CC=C
C(C)C(O[C@@]1(c2ccccc2)[C@H](CC=C)C[NH+](C)CC1)=O
C1[NH+](C)C[C@@H](CC=C)[C@@](OC(CC)=O)(c2ccccc2)C1
C(C)C(=O)O[C@@]1(c2ccccc2)[C@H](CC=C)C[NH+](C)CC1
CCC(O[C@]1(c2ccccc2)CC[NH+](C)C[C@H]1CC=C)=O
C(C(O[C@]1(c2ccccc2)CC[NH+](C)C[C@H]1CC=C)=O)C
Before vectorization SMILES must be stored as strings in an numpy array. The transform takes numpy arrays or pandas series with the SMILES as strings.
import numpy as np
smiles = np.array(["CCC(=O)O[C@@]1(CC[NH+](C[C@H]1CC=C)C)c2ccccc2"])
print(smiles.shape)(1,)
Fit the charset and the padding to the SMILES array, alternatively they can be specified when instantiating the object.
sme.fit(smiles)
print(sme.charset)
print(sme.pad)=2@NH+c]OC([1)
50
There have been added some extra padding to the maximum lenght observed in the smiles array. The SMILES can be transformed to one-hot encoded vectors and showed with matplotlib.
import matplotlib.pyplot as plt
%matplotlib inline
vect = sme.transform(smiles)
plt.imshow(vect[0])<matplotlib.image.AxesImage at 0x7f9cbde54d30>
It's a nice piano roll. If the vectorization is repeated, the vectorization will be different due to the enumeration, as sme.enum and sme.canonical is set to True and False, respectively (default settings).
print(sme.enumerate, sme.canonical)
vect = sme.transform(smiles)
plt.imshow(vect[0])True False
<matplotlib.image.AxesImage at 0x7f9cb5d544c0>
The reverse_transform() function can be used to translate back to a SMILES string, as long as the charset is the same as was used to vectorize.
print(sme.reverse_transform(vect))['CCC(=O)O[C@@]1(c2ccccc2)[C@H](CC=C)C[NH+](C)CC1']
The SmilesEnumerator class can be used together with the SmilesIterator batch generator for on the fly vectorization for RNN modeling of molecules. Below it's briefly demonstrated how this can be done.
import pandas as pd
data = pd.read_csv("Example_data/Sutherland_DHFR.csv")
print(data.head()) Unnamed: 0 smiles_parent PC_uM_sign \
0 0 CCc1nc(N)nc(N)c1-c1ccc(Cl)cc1 NaN
1 1 CCc1nc(N)nc(N)c1-c1ccc(Cl)c(Cl)c1 NaN
2 2 Cc1nc(N)nc(N)c1-c1ccc(Cl)c(Cl)c1 NaN
3 3 CCOCc1nc(N)nc(N)c1-c1ccc(Cl)c(Cl)c1 NaN
4 4 Nc1nc(N)c(-c2ccc(Cl)cc2)c(COc2ccc([N+](=O)[O-]... NaN
PC_uM_value
0 3.70
1 1.08
2 1.68
3 12.70
4 85.10
from sklearn.model_selection import train_test_split
#We ignore the > signs, and use random splitting for simplicity
X_train, X_test, y_train, y_test = train_test_split(data["smiles_parent"],
np.log(data["PC_uM_value"]).values.reshape(-1,1),
random_state=42)
from sklearn.preprocessing import RobustScaler
rbs = RobustScaler(with_centering=True, with_scaling=True, quantile_range=(5.0, 95.0), copy=True)
y_train = rbs.fit_transform((y_train))
y_test = rbs.transform(y_test)
_ = plt.hist(y_train, bins=25)
import tensorflow.keras.backend as K
from SmilesEnumerator import SmilesIterator
#The SmilesEnumerator must be fit to the entire dataset, so that all chars are registered
sme.fit(data["smiles_parent"])
sme.leftpad = True
print(sme.charset)
print(sme.pad)
#The dtype is set for the K.floatx(), which is the numerical type configured for Tensorflow or Theano
generator = SmilesIterator(X_train, y_train, sme, batch_size=200, dtype=K.floatx())3o4n+c-(l5N[s1F=SB2IH]#OrC)
75
X,y = generator.next()
print(X.shape)
print(y.shape)(200, 75, 27)
(200, 1)
Build a SMILES based RNN QSAR model with Keras.
from tensorflow.keras.models import Sequential
from tensorflow.keras.layers import Dense, LSTM
from tensorflow.keras import regularizers
from tensorflow.keras.optimizers import RMSpropinput_shape = X.shape[1:]
output_shape = 1
model = Sequential()
model.add(LSTM(64,
input_shape=input_shape,
dropout = 0.19
#unroll= True
))
model.add(Dense(output_shape,
kernel_regularizer=regularizers.l1_l2(0.005,0.01),
activation="linear"))
model.compile(loss="mse", optimizer=RMSprop(lr=0.005))
print(model.summary())Model: "sequential_4"
_________________________________________________________________
Layer (type) Output Shape Param #
=================================================================
lstm_4 (LSTM) (None, 64) 23552
dense_4 (Dense) (None, 1) 65
=================================================================
Total params: 23,617
Trainable params: 23,617
Non-trainable params: 0
_________________________________________________________________
None
Use the generator object for training.
model.fit_generator(generator, steps_per_epoch=100, epochs=25, workers=4)/tmp/ipykernel_1329301/2098089966.py:1: UserWarning: `Model.fit_generator` is deprecated and will be removed in a future version. Please use `Model.fit`, which supports generators.
model.fit_generator(generator, steps_per_epoch=100, epochs=25, workers=4)
Epoch 1/25
100/100 [==============================] - 8s 67ms/step - loss: 0.1390
Epoch 2/25
100/100 [==============================] - 6s 62ms/step - loss: 0.1065
Epoch 3/25
100/100 [==============================] - 6s 62ms/step - loss: 0.0945
Epoch 4/25
100/100 [==============================] - 6s 62ms/step - loss: 0.0899
Epoch 5/25
100/100 [==============================] - 6s 63ms/step - loss: 0.0853
Epoch 6/25
100/100 [==============================] - 6s 61ms/step - loss: 0.0804
Epoch 7/25
100/100 [==============================] - 6s 62ms/step - loss: 0.0783
Epoch 8/25
100/100 [==============================] - 6s 63ms/step - loss: 0.0800
Epoch 9/25
100/100 [==============================] - 6s 62ms/step - loss: 0.0740
Epoch 10/25
100/100 [==============================] - 6s 61ms/step - loss: 0.0737
Epoch 11/25
100/100 [==============================] - 6s 62ms/step - loss: 0.0716
Epoch 12/25
100/100 [==============================] - 6s 60ms/step - loss: 0.0677
Epoch 13/25
100/100 [==============================] - 6s 62ms/step - loss: 0.0656
Epoch 14/25
100/100 [==============================] - 6s 61ms/step - loss: 0.0636
Epoch 15/25
100/100 [==============================] - 6s 62ms/step - loss: 0.0617
Epoch 16/25
100/100 [==============================] - 6s 62ms/step - loss: 0.0605
Epoch 17/25
100/100 [==============================] - 6s 61ms/step - loss: 0.0592
Epoch 18/25
100/100 [==============================] - 6s 63ms/step - loss: 0.0580
Epoch 19/25
100/100 [==============================] - 6s 61ms/step - loss: 0.0561
Epoch 20/25
100/100 [==============================] - 6s 63ms/step - loss: 0.0555
Epoch 21/25
100/100 [==============================] - 6s 61ms/step - loss: 0.0543
Epoch 22/25
100/100 [==============================] - 6s 62ms/step - loss: 0.0517
Epoch 23/25
100/100 [==============================] - 6s 61ms/step - loss: 0.0553
Epoch 24/25
100/100 [==============================] - 6s 60ms/step - loss: 0.0512
Epoch 25/25
100/100 [==============================] - 6s 63ms/step - loss: 0.0497
<keras.callbacks.History at 0x7f9bdc1a30a0>
y_pred_train = model.predict(sme.transform(X_train))
y_pred_test = model.predict(sme.transform(X_test))
plt.scatter(y_train, y_pred_train, label="Train")
plt.scatter(y_test, y_pred_test, label="Test")
plt.legend()<matplotlib.legend.Legend at 0x7f9bb8162260>
Not the best model until now. However, prolonged training with lowering of the learning rate towards the end will improve the model.
#The Enumerator can be used in sampling
i = 0
y_true = y_test[i]
y_pred = model.predict(sme.transform(X_test.iloc[i:i+1]))
print(y_true)
print(y_true - y_pred)[0.23319628]
[[0.11318717]]
#Enumeration of the SMILES before sampling stabilises the result
smiles_repeat = np.array([X_test.iloc[i:i+1].values[0]]*50)
y_pred = model.predict(sme.transform(smiles_repeat))
print(y_pred.std())
print(y_true - np.median(y_pred))
_ = plt.hist(y_pred)0.037997264
[0.1770267]
Please cite: SMILES enumeration as Data Augmentation for Network Modeling of Molecules
@article{DBLP:journals/corr/Bjerrum17,
author = {Esben Jannik Bjerrum},
title = {{SMILES} Enumeration as Data Augmentation for Neural Network Modeling
of Molecules},
journal = {CoRR},
volume = {abs/1703.07076},
year = {2017},
url = {http://arxiv.org/abs/1703.07076},
timestamp = {Wed, 07 Jun 2017 14:40:38 +0200},
biburl = {http://dblp.uni-trier.de/rec/bib/journals/corr/Bjerrum17},
bibsource = {dblp computer science bibliography, http://dblp.org}
}If you find it useful, feel welcome to leave a comment on the blog.