Dataset Information

Random Forest Modelling of High-Dimensional Mixed-Type Data for Breast Cancer Classification.

ABSTRACT: Advances in high-throughput technologies encourage the generation of large amounts of multiomics data to investigate complex diseases, including breast cancer. Given that the aetiologies of such diseases extend beyond a single biological entity, and that essential biological information can be carried by all data regardless of data type, integrative analyses are needed to identify clinically relevant patterns. To facilitate such analyses, we present a permutation-based framework for random forest methods which simultaneously allows the unbiased integration of mixed-type data and assessment of relative feature importance. Through simulation studies and machine learning datasets, the performance of the approach was evaluated. The results showed minimal multicollinearity and limited overfitting. To further assess the performance, the permutation-based framework was applied to high-dimensional mixed-type data from two independent breast cancer cohorts. Reproducibility and robustness of our approach was demonstrated by the concordance in relative feature importance between the cohorts, along with consistencies in clustering profiles. One of the identified clusters was shown to be prognostic for clinical outcome after standard-of-care adjuvant chemotherapy and outperformed current intrinsic molecular breast cancer classifications.

SUBMITTER: Quist J

PROVIDER: S-EPMC7956671 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Publications

Random Forest Modelling of High-Dimensional Mixed-Type Data for Breast Cancer Classification.

Quist Jelmar J Taylor Lawson L Staaf Johan J Grigoriadis Anita A

Cancers 20210227 5

Advances in high-throughput technologies encourage the generation of large amounts of multiomics data to investigate complex diseases, including breast cancer. Given that the aetiologies of such diseases extend beyond a single biological entity, and that essential biological information can be carried by all data regardless of data type, integrative analyses are needed to identify clinically relevant patterns. To facilitate such analyses, we present a permutation-based framework for random fores ...[more]

PMID: 33673506

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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

Random Forest Modelling of High-Dimensional Mixed-Type Data for Breast Cancer Classification.

Publications

Random Forest Modelling of High-Dimensional Mixed-Type Data for Breast Cancer Classification.

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