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Xenakis, J.

Publications and source records attributed to Xenakis, J..

2 recordsLinked to original sources

A Deep Neural Network Two-part Model and Feature Importance Test for Semi-continuous Data

Semi-continuous data frequently arise in clinical practice. For example, while many surgical patients suffer from varying degrees of acute postoperative pain (POP) post surgery (i.e., POP score > 0), others experience none (i.e., POP score = 0), indicating the existence of two distinct data processes at play. Existing parametric or semi-parametric two-part modeling methods for this type of semicontinuous data can fail to appropriately model these two underlying data processes as such methods rely heavily on (generalized) linear additive assumptions. However, many factors may interact to jointly influence the experience of POP non-additively and non-linearly. Motivated by this challenge and inspired by the flexibility of deep neural networks (DNN) to accurately approximate complex functions universally, we derive a DNN-based two-part model by adapting the conventional DNN methods by adding two additional components: a bootstrapping procedure along with a filtering algorithm to boost the stability of the conventional DNN, an approach we denote as sDNN. To improve the interpretability and transparency of sDNN, we further derive a feature importance testing procedure to identify important features contributing to the outcome measurements of the two data processes, denoting this approach fsDNN. We show that fsDNN not only offers a valid feature importance test but also that using the identified features can further improve the predictive performance of sDNN. The proposed sDNN- and fsDNN-based twopart models are applied to the analysis of real data from a POP study, in which application they clearly demonstrate advantages over the existing parametric and semi-parametric two-part models. Further, we conduct extensive numerical studies to demonstrate that sDNN and fsDNN consistently outperform the existing two-part models regardless of the data complexity. An R package implementing the proposed methods has been developed and deposited on GitHub (https://github.com/SkadiEye/fsDNN).

bioinformatics↗

Antipsychotic behavioral phenotypes in the mouse Collaborative Cross recombinant inbred inter-crosses (RIX)

Schizophrenia is an idiopathic disorder that affects approximately 1% of the human population, and presents with persistent delusions, hallucinations, and disorganized behaviors. Antipsychotics are the standard pharmacological treatment for schizophrenia, but are frequently discontinued by patients due to inefficacy and/or side effects. Chronic treatment with the typical antipsychotic haloperidol causes tardive dyskinesia (TD), which manifests as involuntary and often irreversible orofacial movements in around 30% of patients. Mice treated with haloperidol develop many of the features of TD, including jaw tremors, tongue protrusions, and vacuous chewing movements (VCMs). In this study, we used genetically diverse Collaborative Cross (CC) recombinant inbred inter-cross (RIX) mice to elucidate the genetic basis of antipsychotic-induced adverse drug reactions (ADRs). We performed a battery of behavioral tests in 840 mice from 73 RIX lines (derived from 62 CC strains) treated with haloperidol or placebo in order to monitor the development of ADRs. We used linear mixed models to test for strain and treatment effects. We observed highly significant strain effects for almost all behavioral measurements investigated (p<0.001). Further, we observed strong strain-by-treatment interactions for most phenotypes, particularly for changes in distance traveled, vertical activity, and extrapyramidal symptoms (EPS). Estimates of overall heritability ranged from 0.21 (change in body weight) to 0.4 (VCMs and change in distance traveled) while the portion attributable to the interactions of treatment and strain ranged from 0.01 (for change in body weight) to 0.15 (for change in EPS). Interestingly, close to 30% of RIX mice exhibited VCMs, a sensitivity to haloperidol exposure, approximately similar to the rate of TD in humans chronically exposed to haloperidol. Understanding the genetic basis for the susceptibility to antipsychotic ADRs may be possible in mouse, and extrapolation to humans could lead to safer therapeutic approaches for schizophrenia.

systems biology↗