Machine Learning in Medicine
The Clinical Research Unit provides a blue print for using machine learning in medicine
Method & Analytics Team  by Zara Aminolroaya, under supervision of Cord LethebeThe applications of machine learning (ML) to address medical field problems and the healthcare industry are increasing day by day. The Clinical Research Unit has provided the following article, which explains the difference between machine learning and statistics, steps to use machine learning, and different applications of machine learning in the medical field.
Intro  Machine Learning vs. Statistics
Machine learning is making healthcare smarter, but oldschool statistics still has its place in healthcare analytics. There are different criteria for choosing between machine learning or statistical analytics, such as the analytics goal, the size of data, the number of variables, etcetera.
Machine learning and statistical learning are nearly related in many aspects and are more or less the same, but they consider different perspectives on the same problem:
Statistics: Statistics is defined as the study of collection, analysis, interpretation, presentation, and organization of data.
Machine Learning: Machine learning gives computers the ability to learn without being explicitly programmed.
The following is a comparison of these two techniques based on the purpose of data analysis.
Machine Learning  Statistical Modeling 



Statistical models are often easier to interpret, and they are suitable for the description of the biological relationships when the features have mainly an additive effect. Machine learning is suitable for prediction and decision making about new data. ML is promising in the areas that are not traditional “tabular data”, such as images.
Formulation
The formulation of machine learning and statistical modeling is different even with the same end goal.
In a statistical model, we basically try to estimate the function f in:
Dependent Variable ( Y ) = f(Independent Variable) + error function
Machine Learning takes away the deterministic function “f” out of the equation. It simply becomes:
Output(Y)  > Input (X)
It will try to find pockets of X in n dimensions (where n is the number of attributes), where occurrence of Y is significantly different.
Language
A major difference between statistics and machine learning is their languages. Some terms can have similar meaning in statistics and machine learning but with different languages:
Machine Learning  Statistics 

Sample/ instance  Subject/ observation 
Target  Outcome Variable 
Learning  Estimation 
Example/ instance  Data point 
Supervised Learning  Regression 
Softmax  Multinomial Regression 
Supervised Learning  Classification 
Feature  Covariates 
Label  Response 
Graph/ network  Model 
Weights  Parameters 
Generalization  Test set performance 
Loss  Logliklihood 
Noise  Measurement error 
Onehot encoding  Dummy coding 
Precision  Positive predictive value 
Confusion Matrix  Contingency table 
Groundtruth  Gold standard 
Big vs. Small Data
For better performance, machine learning models need more data than statistical models. Powerful predictive models, such as neural networks and random forests, usually use datasets in the scales of thousands and millions for suitable performance. In contrast, statistical models often can infer and make predictions on hundreds of observations
Many vs. Few Variables
Machine learning models select between variables based on their relevance to the outcome, but statistical models are generally not like ML models. In fact, when there are more predictor variables than observations (for example, when using many genes’ status as predictors), statistical models fail completely, while machine learning models proceed unphased.
Machine Learning Step by Step
When using machine learning for addressing a problem, it is important to become familiar with different areas in ML. Each area includes different topics:
Now, let's look at one of the road maps to apply machine learning for addressing a specific problem. Choosing a suitable machine learning algorithm for the problem depends on different factors, such as the nature of the data, computational time, etc.
The following sections discuss important concepts relating to different steps for choosing machine learning algorithms.
Supervised Learning vs. Unsupervised Learning
Supervised Learning
In supervised learning, a labeled dataset is ready for training. In fact, it is known what the outcome should look like.
Supervised Learning problems are broadly categorized as regression and classification problems.
Regression Problem
In a regression problem, results are predicted within a continuous output, meaning that we are trying to map input variables to some continuous function. The metrics that are commonly minimized/maximized in the model fit stage for regression problems are the Mean Squared Error (MSE), Mean Absolute Error (MAE), R^{2}, etc.
Most popular regression algorithms are:
 Linear Regression
 Logistic Regression
 Polynomial Regression
 Stepwise Regression
 Ridge Regression
 Lasso Regression
 ElasticNet Regression
Classification Problem
In a classification problem, input variables are into discrete categories. A classification model attempts to draw some conclusions from observed values. Given one or more inputs, a classification model will try to predict the value of one or more outcomes. The metrics that are commonly minimized/maximized in classification problems are the misclassification rate, Area Under the Receiver Operating Characteristic curve (AUROC or AUC), F1score, sensitivity, specificity, etc.
There are two types of classification analysis:
 Binomial Classification
 Multiclass Classification
Binary or binomial classification is the task of classifying the elements of a given set into two groups
Popular algorithms: Lasso Logistic Regression, Decision trees, Random Forest, Bayesian networks, Support vector machines, Neural networks
Multiclass classification is a classification task with more than two classes.
Popular algorithms: Multinomial logit, Decision trees, Random Forest, Bayesian networks, Support vector machines, Neural networks, Nearest neighbor
The following image shows the difference between classification and regression:
Unsupervised Learning
Unsupervised learning is a type of machine learning algorithm used to draw inferences from datasets consisting of input data without labeled responses. The most common unsupervised learning method is cluster analysis, which is used for exploratory data analysis to find hidden patterns or grouping in data. Also, dimension reduction is considered as unsupervised learning, in which the variables of data are reduced based on the relationships between datasets.
Clustering Algorithms
Most popular clustering algorithms are:
 Partitioning methods
 Hierarchical clustering
 Fuzzy clustering
 Densitybased clustering
 Modelbased clustering
The below image shows the difference between hierarchical and nonhierarchical clusterings.
Dimensional Reduction
Some variables (features) are redundant or irrelevant according to the prediction. With the dimension reduction, the true relationship between features and the outcome can be identified.
ML Algorithms
Description
Polynomial regression is a form of regression analysis in which the relationship between the independent variable x and the dependent variable y is modelled as an nth degree polynomial in x.
Data Requirement
Obervations must be independant
Complexity
Calling 𝑛 the number of observations and p the number of weights, the overall complexity should be 𝑛^2 𝑝+ 𝑝^3. Execution time of the algorithms is highly related to different factors such as Hardware, optimization, etc. for example, in Rule Based Systems in a Distributed Environment, they could run the logistic regression algorithms for 100 GB data with 100 machine for less than 70 s.
Interpretability
Regressions are interpretable. The relationship between x and y is totally observable.
Description
Lasso (least absolute shrinkage and selection operator; also Lasso or LASSO) is a regression analysis method that performs both variable selection and regularization in order to enhance the prediction accuracy and interpretability of the statistical model it produces.
Data Requirement
Lasso regression puts constraints on the size of the coefficients associated to each variable. However, this value will depend on the magnitude of each variable. It is therefore necessary to center and reduce, or standardize, the variables.
Complexity
Let the number of candidate variables (features, columns) be 𝐾 and the sample size (number of observations, rows) be 𝑛. Consider LASSO implemented using LARS algorithm. The computational complexity of LASSO is 𝑘^3+ 𝑘^2 𝑛.
Interpretability
Interpretability decreases if the target is dependent on lot of features
Description
Kmeans algorithms can be used to subdivide data points of a dataset into clusters based on nearest mean values. To determine the optimal division of your data points into clusters, such that the distance between points in each cluster is minimized, kmeans clustering would be appropriate algorithms. In the term kmeans, k denotes the number of clusters in the data.
Data Requirement
The type of data best suited for KMeans clustering would be numerical data with a relatively lower number of dimensions.
Complexity
Kmean is NP hard problem. O(kn) for each iteration where k = no. of cluster, n = no. of points. For example based on An Improved Mini Batch Kmeans Algorithm Based on Mapreduce with Big Data the running time for 1 million data is 100 S or for 9 million is about 400 S.
Interpretability
Groups of data are recognizable after clustering.
Description
Logistic regression is the appropriate regression analysis to conduct when the dependent variable is dichotomous (binary). Like all regression analyses, the logistic regression is a predictive analysis. Logistic regression is used to describe data and to explain the relationship between one dependent binary variable and one or more nominal, ordinal, interval or ratiolevel independent variables.
Data Requirement
Logistic regression does not require a linear relationship between the dependent and independent variables. Also, the error terms (residuals) do not need to be normally distributed. Finally, the dependent variable in logistic regression is not measured on an interval or ratio scale.
Complexity
Complexity of training for logistic regression methods with gradient based optimization: O((f+1)csE), where:
 f  number of features (+1 because of bias). Multiplication of each feature times it's weight (foperations, +1 for bias). Another f + 1 operations for summing all of them (obtaining prediction). Using gradient method to improve weights counts for the same number of operations, so in total we get 4* (f+1) (two for forward pass, two for backward), which is simply O(f+1).
 c  number of classes (possible outputs) in your logistic regression. For binary classification it's one, so this term cancels out. Each class has it's corresponding set of weights.
 s  number of samples in your dataset, this one is quite intuitive I think.
 E  number of epochs you are willing to run the gradient descent (whole passes through dataset)
Note: this complexity can change based on things like regularization (another c operations), but the idea standing behind it goes like this.
Interpretability
The formulation of logistic regression in terms of log odds is the fundamental reason why logistic regression coefficients aren't interpretable. logistic regression isn't completely a black box: The linearity assumption means that you can compare the relative impact of the covariates by their coefficients, (assuming you've appropriately scaled the covariates). And the impact of changing a covariate depends only upon current estimated probability and the magnitude of the change, (in more complex models it can depend on the current values of all of the covariates).
Description
A decision tree is a decision support tool that uses a treelike model of decisions and their possible consequences, including chance event outcomes, resource costs, and utility.
Data Requirement
Decision trees can handle both categorical and numerical data.
Complexity
Let 𝑁 = number of training examples, 𝑘= number of features, and 𝑑 = depth of the decision tree. The time complexity for decision trees is in 𝑂(𝑁𝑘𝑑) .
Interpretability
It is highly interpretable. Different Decisions are observable.
Description
A neural network is a series of algorithms that endeavors to recognize underlying relationships in a set of data through a process that mimics the way the human brain operates.
Data Requirement
Need a large large dataset.
Complexity
The complexity for learning 𝑚 examples, where each gets repeated 𝑒 times, and where 𝑤 is the number of weights, is (𝑤∗𝑚∗𝑒).
Interpretability
Neural networks are not considered to be interpretable.
Description
A Support Vector Machine (SVM) is a discriminative classifier formally defined by a separating hyperplane. In other words, given labeled training data (supervised learning), the algorithm outputs an optimal hyperplane which categorizes new examples.
Data Requirement
Data should be numerical.
Complexity
Linear SVM has prediction complexity 𝑂(𝑑) with 𝑑 is the number of input dimensions since it is just a single inner product. The followings illustrate SVM algorithms runt time based on the number of datasets.
Interpretability
Linear SVMs are also interpretable as any other linear model, since each input feature has a weight that directly influences the model output. Nonlinear SVMs are partially interpretable, as they tell you which training data are relevant for prediction, and which aren't. This is not possible for other methods such as Random Forests or Deep Networks.
Description
Bayesian networks are a type of probabilistic graphical model that uses Bayesian inference for probability computations. Bayesian networks aim to model conditional dependence, and therefore causation, by representing conditional dependence by edges in a directed graph. Through these relationships, one can efficiently conduct inference on the random variables in the graph through the use of factors.
Data Requirement
Data should be categorical.
Complexity
It is NP hard.
Interpretability
Bayesian networks are visually interpretable.
Tools
Some machine learning and data mining tools that require minimal experience include:
For working with more powerful tools as below, some data mining and programming experience is required:
Interpretability Vs. Accuracy
There is a tradeoff between the predictive accuracy of a model and how easy the model is to interpret. For example, linear regression is a simple model with a few parameters which is easy to interpret. However, it may not have sufficient predictive power for particular use cases. On the other hand, models like neural networks with millions of parameters will often highly perform for prediction. However, these complex models do not always make business sense and it would be hard to explain to clients how models made decisions.
It is important to deliver a project to a business client and build confidence in the algorithmic approaches. There are different ways to increase the understandability of machine learning results for a client user. One of them is to explain how different inputs affect the model's performance.
Machine Learning in Medicine
Research Purpose
There are different research purposes in the medicine field, and machine learning proposes different techniques to solve problems in each area:
Diagnostic
Medical diagnosis is the process of determining which disease or condition explains a person's symptoms and signs. Machine learning is being used to diagnose cancer, pneumonia, and other diseases, and with enough reliable datasets, it is often more accurate and faster at diagnosis than real doctors. Diagnostic problems can be solved by classification methods. For example, the below image shows the high algorithm performance on detecting the lung cancer
Prediction
Predictive analytics is the process of learning from historical data in order to make predictions about the future (or any unknown). For health care, predictive analytics will enable the best decisions to be made. Prediction problems can be solved by classification or regression methods.
Frequency
Frequency is used for epidemiological measurements to describe the occurrence of disease. Frequency problems can be solved by regression methods.
Association
Association is a statistical relationship between two or more events, characteristics or other variables  e.g., an association between exposure to X and a health effect, Y  which may not imply cause and effect. Association problems can be solved by regression methods.
Finding Similar Groups
Clustering can be used for finding similar groups of different elements and it is the process of analyzing, examining relationships in, and organizing theoretically the current knowledge in a field of study in order to add to an existing knowledge base and generate further questions for research. Clustering methods can be used for finding similar groups. For example, the below image shows the heatmap analysis of microarray data showing hierarchical clustering of differentially expressed genes.
Health Data Types
The number of digitized health and wellness data increases day by day, which makes the opportunity for analyzing data through data science and machine learning methods. For data analysis, due to the complexity of the human condition, the data related to a patient would often be retrieved and integrated from multiple sources and should be analyzed from different aspects. Combining data from various resources, such as hospitals, clinics, etc., contributes to earning valuable knowledge. With the increase of the data size, some big data approaches should be considered in conjunction with machine learning algorithms to solve a problem.
In the following, there is an organization of data types relating to different health and wellness sources.
Summary
In the medicine field, it is common to use statistical analytics and machine learning to solve problems based on a problem target and data features. This article looks at different concepts of machine learning and refers to different areas in ML. Finally, the article explains the use of machine learning techniques based on the research purposes in the medicine field.