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A new approach for interpreting Random Forest models and its application to the biology of ageing.

ABSTRACT: Motivation:This work uses the Random Forest (RF) classification algorithm to predict if a gene is over-expressed, under-expressed or has no change in expression with age in the brain. RFs have high predictive power, and RF models can be interpreted using a feature (variable) importance measure. However, current feature importance measures evaluate a feature as a whole (all feature values). We show that, for a popular type of biological data (Gene Ontology-based), usually only one value of a feature is particularly important for classification and the interpretation of the RF model. Hence, we propose a new algorithm for identifying the most important and most informative feature values in an RF model. Results:The new feature importance measure identified highly relevant Gene Ontology terms for the aforementioned gene classification task, producing a feature ranking that is much more informative to biologists than an alternative, state-of-the-art feature importance measure. Availability and implementation:The dataset and source codes used in this paper are available as 'Supplementary Material' and the description of the data can be found at: https://fabiofabris.github.io/bioinfo2018/web/. Supplementary information:Supplementary data are available at Bioinformatics online.

SUBMITTER: Fabris F

PROVIDER: S-EPMC6041990 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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A new approach for interpreting Random Forest models and its application to the biology of ageing.

Fabris Fabio F Doherty Aoife A Palmer Daniel D de Magalhães João Pedro JP Freitas Alex A AA

Bioinformatics (Oxford, England) 20180701 14

<h4>Motivation</h4>This work uses the Random Forest (RF) classification algorithm to predict if a gene is over-expressed, under-expressed or has no change in expression with age in the brain. RFs have high predictive power, and RF models can be interpreted using a feature (variable) importance measure. However, current feature importance measures evaluate a feature as a whole (all feature values). We show that, for a popular type of biological data (Gene Ontology-based), usually only one value o ...[more]

PMID: 29462247

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Project description:BackgroundNon-additive interactions among genes are frequently associated with a number of phenotypes, including known complex diseases such as Alzheimer's, diabetes, and cardiovascular disease. Detecting interactions requires careful selection of analytical methods, and some machine learning algorithms are unable or underpowered to detect or model feature interactions that exhibit non-additivity. The Random Forest method is often employed in these efforts due to its ability to detect and model non-additive interactions. In addition, Random Forest has the built-in ability to estimate feature importance scores, a characteristic that allows the model to be interpreted with the order and effect size of the feature association with the outcome. This characteristic is very important for epidemiological and clinical studies where results of predictive modeling could be used to define the future direction of the research efforts. An alternative way to interpret the model is with a permutation feature importance metric which employs a permutation approach to calculate a feature contribution coefficient in units of the decrease in the model's performance and with the Shapely additive explanations which employ cooperative game theory approach. Currently, it is unclear which Random Forest feature importance metric provides a superior estimation of the true informative contribution of features in genetic association analysis.ResultsTo address this issue, and to improve interpretability of Random Forest predictions, we compared different methods for feature importance estimation in real and simulated datasets with non-additive interactions. As a result, we detected a discrepancy between the metrics for the real-world datasets and further established that the permutation feature importance metric provides more precise feature importance rank estimation for the simulated datasets with non-additive interactions.ConclusionsBy analyzing both real and simulated data, we established that the permutation feature importance metric provides more precise feature importance rank estimation in the presence of non-additive interactions.

Project description:Neural mass models (NMMs) are increasingly used to uncover the large-scale mechanisms of brain rhythms in health and disease. The dynamics of these models is dependent upon the choice of parameters, and therefore it is crucial to be able to understand how dynamics change when parameters are varied. Despite being considered low dimensional in comparison to micro-scale, neuronal network models, with regards to understanding the relationship between parameters and dynamics, NMMs are still prohibitively high dimensional for classical approaches such as numerical continuation. Therefore, we need alternative methods to characterise dynamics of NMMs in high dimensional parameter spaces. Here, we introduce a statistical framework that enables the efficient exploration of the relationship between model parameters and selected features of the simulated, emergent model dynamics of NMMs. We combine the classical machine learning approaches of trees and random forests to enable studying the effect that varying multiple parameters has on the dynamics of a model. The method proceeds by using simulations to transform the mathematical model into a database. This database is then used to partition parameter space with respect to dynamic features of interest, using random forests. This allows us to rapidly explore dynamics in high dimensional parameter space, capture the approximate location of qualitative transitions in dynamics and assess the relative importance of all parameters in the model in all dimensions simultaneously. We apply this method to a commonly used NMM in the context of transitions to seizure dynamics. We find that the inhibitory sub-system is most crucial for the generation of seizure dynamics, confirm and expand previous findings regarding the ratio of excitation and inhibition, and demonstrate that previously overlooked parameters can have a significant impact on model dynamics. We advocate the use of this method in future to constrain high dimensional parameter spaces enabling more efficient, person-specific, model calibration.

Dataset Information

A new approach for interpreting Random Forest models and its application to the biology of ageing.

Publications

A new approach for interpreting Random Forest models and its application to the biology of ageing.

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