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A guide to machine learning for biologists

Abstract

The expanding scale and inherent complexity of biological data have encouraged a growing use of machine learning in biology to build informative and predictive models of the underlying biological processes. All machine learning techniques fit models to data; however, the specific methods are quite varied and can at first glance seem bewildering. In this Review, we aim to provide readers with a gentle introduction to a few key machine learning techniques, including the most recently developed and widely used techniques involving deep neural networks. We describe how different techniques may be suited to specific types of biological data, and also discuss some best practices and points to consider when one is embarking on experiments involving machine learning. Some emerging directions in machine learning methodology are also discussed.

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Fig. 1: Choosing and training a machine learning method.
Fig. 2: Training machine learning methods.
Fig. 3: Traditional machine learning methods.
Fig. 4: Neural network methods.

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Acknowledgements

The authors thank members of the UCL Bioinformatics Group for valuable discussions and comments. This work was supported by the European Research Council Advanced Grant ProCovar (project ID 695558).

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All authors researched data for the article, contributed substantially to discussion of the content, wrote the article and reviewed the manuscript before submission.

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Correspondence to David T. Jones.

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Glossary

Deep learning

Machine learning methods based on neural networks. The adjective ‘deep’ refers to the use of many hidden layers in the network, two hidden layers as a minimum but usually many more than that. Deep learning is a subset of machine learning, and hence of artificial intelligence more broadly.

Artificial neural networks

A collection of connected nodes loosely representing neuron connectivity in a biological brain. Each node is part of a layer and represents a number calculated from the previous layer. The connections, or edges, allow a signal to flow from the input layer to the output layer via hidden layers.

Ground truth

The true value that the output of a machine learning model is compared with to train the model and test performance. These data usually come from experimental data (for example, accessibility of a region of DNA to transcription factors) or expert human annotation (for example healthy or pathological medical image).

Encoding

Any scheme for numerically representing (often categorical) data in a form suitable for use in a machine learning model. An encoding can be a fixed numerical representation (for example, one-hot or continuous encoding) or can be defined using parameters that are trained along with the rest of a model.

One-hot encoding

An encoding scheme that represents a fixed set of n categorical inputs using n unique n-dimensional vectors, each with one element set to 1 and the rest set to 0. For example, the set of three letters (A,B,C) could be represented by the three vectors [1,0,0], [0,1,0] and [0,0,1], respectively.

Mean squared error

A loss function that calculates the average squared difference between the predicted values and the ground truth. This function heavily penalizes outliers because it increases rapidly as the difference between a predicted value and the ground truth grows.

Binary cross entropy

The most common loss function for training a binary classifier; that is, for tasks aimed at answering a question with only two choices (such as cancer versus non-cancer); sometimes called ‘log loss’.

Linear regression

A model that assumes that the output can be calculated from a linear combination of inputs; that is, each input feature is multiplied by a single parameter and these values are added. It is easy to interpret how these models make their predictions.

Kernel functions

Transformations applied to each data point to map the original points into a space in which they become separable with respect to their class.

Non-linear regression

A model where the output is calculated from a non-linear combination of inputs; that is, the input features can be combined during prediction using operations such as multiplication. These models can describe more complex phenomena than linear regression.

k nearest neighbours

A classification approach where a data point is classified on the basis of the known (ground truth) classes of the k most similar points in the training set using a majority voting rule. k is a parameter that can be tuned. Can also be used for regression by averaging the property value over the k nearest neighbours.

Regularization

Restricting the values of parameters to prevent the model from overfitting to the training data. For example, penalizing high parameter values in regression models reduces the flexibility of the model and can stop it fitting to noise in the training data.

Cloud computing

On-demand computing services, including processing power and data storage, typically available via the Internet. A pay-as-you-go model is usually used. Use of cloud computing minimizes up-front IT infrastructure costs.

Hidden Markov model

A statistical model that can be used to describe the evolution of observable events that depend on factors that are not directly observable. It has various uses in biology, including representing protein sequence families.

Saliency map

In the context of machine learning, an image generated to show which pixels in an input image contribute to the prediction made by a model. It is useful in interpreting models.

Automatic differentiation

A set of techniques to automatically calculate the gradient of a function in a computer program. Used to train neural networks, where it is called ‘backpropagation’.

Gradients

The rate of change of one property as another property changes. In neural networks, the set of gradients of the loss function with respect to the neural network parameters, computed via a process known as backpropagation, is used to adjust the parameters and thus train the model.

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Greener, J.G., Kandathil, S.M., Moffat, L. et al. A guide to machine learning for biologists. Nat Rev Mol Cell Biol (2021). https://doi.org/10.1038/s41580-021-00407-0

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