Monday, March 22, 2021

Can machine learning regression extrapolate?

I recently developed a ML model to predict pIC50 values for molecules and used it together with a genetic algorithm code to search for molecules with large pIC50 values. However, the GA searches never found molecules with pIC50 values that where larger than in my training set. 

This brought up the general question of whether ML models are capable of outputting values that are larger than those found in the training set. I made a simple example to investigate this issue for different ML models.

$\mathbf{X}_1 = (1, 0, 0)$ corresponds to 1, $\mathbf{X}_2 = (0, 1, 0)$ corresponds to 2, and $\mathbf{X}_3 = (0, 0, 1)$ corresponds to 3.

The code can be found here. If you are new to ML check out this site

Linear Regression
This training set can be fit by a linear regression model $y = \mathbf{wX}$ with the weights $\mathbf{w} = (1, 2, 3)$. Clearly this simple ML can extrapolate in the sense that, for example, $\mathbf{X} = (1, 0, 1)$ will yield 4, which is larger than max value in the training set (3). Similarly, $\mathbf{X} = (0, 0, 2)$ will yield 6.

Neural Network
Next I tried a NN with one hidden layer with 2 nodes and the sigmoid activation function. For this model $\mathbf{X} = (1, 0, 1)$ yields 1.6 and $\mathbf{X} = (0, 0, 2)$ yields 3.2, which is only slightly larger than 3. 

The output of the NN is given by $\mathbf{O}_h\mathbf{w}_{ho}+\mathbf{b}_{ho}$, where $\mathbf{O}_h$ is the output of the hidden layer. Using the sigmoid function, the maximum value of $\mathbf{O}_h = (1, 1)$, for which $\mathbf{O}_h\mathbf{w}_{ho}+\mathbf{b}_{ho}$ = 3.3. So this is the maximum value this NN can output. For comparison, $\mathbf{O}_h = (0.99, 0.65)$ for $\mathbf{X}_3 = (0, 0, 1)$.

If I instead use the ReLU activation function (which doesn't have an upper bound), $\mathbf{X} = (1, 0, 1)$ yields 2.2 and $\mathbf{X} = (0, 0, 2)$ yields 4.2, which is somewhat larger than 3. 

So, NNs that exclusively use ReLU can in principle yield values that are larger than those found in the training set. But if one layer uses bounded activation functions such as sigmoid, then it depends on how close the outputs of that layer are to 1 when predicting the largest value in the training set.

Random Forest
The example is so simple that it can be fit with a single decision tree (RF outputs the mean prediction of a collection of such decision trees):

Clearly the RF can only output values in the range of the training set.

This work is licensed under a Creative Commons Attribution 4.0

Friday, January 8, 2021

Open access chemistry publishing options in 2021


Here is an updated list of affordable impact neutral and other select OA publishing options for chemistry

Impact neutral journals
\$1000 Results in Chemistry. Closed peer review

\$1195 PeerJ Chemistry journals. Open peer review. (Disclaimer I am an editor for PeerJ Physical Chemistry). PeerJ also has a membership model, which may be cheaper than the APC.

\$1195 PeerJ - Life and Environment. Open peer review. Bio-related. PeerJ also has a membership model, which may be cheaper than the APC.

\$1250 ACS Omega. Closed peer review. 

\$1350 F1000Research. Open peer review. Bio-related

(The RSC manages "the journal’s chemistry section by commissioning articles and overseeing the peer-review process")

$1695 PLoS ONE. Closed peer review.

$1990 Scientific Reports. Closed peer review

Free or reasonably priced journals that judge perceived impact
$0 Chemical Science Closed peer review

$0 CCS Chemistry Closed peer review

$0 Beilstein Journal of Organic Chemistry. Closed peer review.

$0 Beilstein Journal of Nanotechnology. Closed peer review.

$0 SciPost Chemistry Open peer review. (Disclaimer: I am an editor for SciPost)

$0 SciPost Chemistry Core Open peer review. (Disclaimer: I am an editor for SciPost)

$0 Digital Discovery Open peer review.

\$0 ACS Central Science. Open peer review. ($1000 for CC-BY)

$100 Living Journal of Computational Molecular Science. Closed peer review

€500 Chemistry2. Closed peer review.

£750 RSC Advances. Closed peer review.

Let me know if I have missed anything.

This work is licensed under a Creative Commons Attribution 4.0