Abstract

Translational research of many disease areas requires a longitudinal understanding of disease development and progression across all biologically relevant scales. Several corresponding studies are now available. However, to compile a comprehensive picture of a specific disease, multiple studies need to be analyzed and compared. A large number of clinical studies is nowadays conducted in the context of drug development in pharmaceutical research. However, legal and ethical constraints typically do not allow for sharing sensitive patient data. In consequence there exist data “silos”, which slow down the overall scientific progress in translational research. In this paper, we suggest the idea of a virtual cohort (VC) to address this limitation. Our key idea is to describe a longitudinal patient cohort with the help of a generative statistical model, namely a modular Bayesian Network, in which individual modules are represented as sparse autoencoder networks. We show that with the help of such a model we can simulate subjects that are highly similar to real ones. Our approach allows for incorporating arbitrary multi-scale, multi-modal data without making specific distribution assumptions. Moreover, we demonstrate the possibility to simulate interventions (e.g. via a treatment) in the VC. Overall, our proposed approach opens the possibility to build sufficiently realistic VCs for multiple disease areas in the future.

Highlights

  • We suggest a conservative approach to simulate virtual patients, which allows for scoring virtual subjects compared to the distribution of real patients and potentially rejecting them, if they might be considered as outliers. Using this approach we demonstrate that our simulated Alzheimer’s (AD) and Parkinson’s Disease (PD) virtual cohort (VC) cannot be reliably discriminated from real patients in Alzheimer’s Disease Neuroimaging Initiative (ADNI) and Parkinson’s Progression Markers Initiative (PPMI)

  • The primary goal of ADNI has been to test whether serial magnetic resonance imaging (MRI), positron emission tomography (PET), other biological markers, and clinical and neuropsychological assessment can be combined to measure the progression of mild cognitive impairment (MCI) and early Alzheimer’s disease (AD)

  • To our knowledge this paper demonstrates for the first time a realistic simulation of virtual clinical subject trajectories across multiple biological scales and data modalities outside the area of mechanistically well understood biological processes

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Summary

Introduction

We discretize the data to enable efficient BN structure and parameter learning for arbitrary statistical distributions and non-linear dependencies between variable groups. We compared our proposed conservative simulation approach to drawing virtual patients directly from the BN model fitted to the entire data.

Results
Conclusion
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