PolyNet

Exploring disease trajectories and outcome prediction using novel methods in network analysis and machine learning

Started
January 1, 2021
Status
Completed
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Abstract

T2DM is the fasting growing chronic disease worldwide and poses a substantial burden to the patient and healthcare system. Thus, the clinical management of T2DM is of global concern. However, due to the complex nature of the disease progression, the relationship between comorbidities and glycemic control remain poorly understood. The ability to improve our understanding of the common disease trajectories starting from diagnosis would provide new insights into disease phenotypes, risk factors, and provide opportunities to develop personalized treatment plans. Additionally, one clinical area of concern within diabetes management is the risk of fragility fractures. While patients with T2DM often have normal or even increased BMD, studies consistently show these patients have an increased risk of fragility fracture. While a number of studies have examined common fracture risk factors for fracture, observational and animal studies are conflicting. Thus, we aim to explore new methods to capture the complex and dynamic nature of patient trajectories. To achieve this aim, this collaboration grant will bring together experts in pharmacoepidemiology, real-world data analytics, social network analysis, and machine learning to develop interpretable models that will serve as an important step towards identifying high-risk patients and subsequently prevent adverse health outcomes. In particular, PolyNet has two primary research objectives to solve the above identified gaps in T2DM care: 1) To explore new methodologies to characterize and visualize common disease and comorbidity trajectories in patients, and 2) To develop longitudinal models to address important clinical questions in T2DM – predicting glycemic control changes and fragility fracture risk. All projects will leverage data from the world’s largest primary care database, the UK Clinical Practice Research Datalink.

People

Collaborators

SDSC Team:
Izabela Moise
Victor Cohen
Anna Susmelj
Alessandro Mari
Ekaterina Krymova
Guillaume Obozinski
Fernando Perez-Cruz

PI | Partners:

ETH Zurich, Pharmacoepidemiology Group, Institute of Pharmaceutical Sciences:

  • Prof. Andrea Burden
  • Adrian Martinez de la Torre
  • Maria Luísa Marques de Sá Faquetti

More info

ETH Zurich, Social Network Lab:

  • Prof. Christoph Stadtfeld

More info

description

Motivation

The goal above all is to address the question: Can we better understand, and ultimately prevent, the development of complex comorbidities and adverse health events in T2DM? To accomplish this overarching goal, we identified two primary goals. First, to identify common trajectories of TD2M progression, comorbidity development and medication use over time. The second goal is to understand the interactions,  to develop machine learning models predicting changes in glycemic control and fragility fracture risk.

Solution

We selected 58 chronic comorbidities of interest and used Bayesian nonparametric models to identify disease clusters. The latent feature models was able to automatically infer the number of binary latent features from the data. Further analysis of the clusters showed that presence of the certain comorbidities can lead to a dramatic increase in chances of developing other conditions. For modeling the progression of comorbidities over time we proposed the structural FHMM, which allowed to analyze the disease trajectories.

Impact

Our models identified established T2DM complications and previously unknown connections, thus, highlighting the potential for ML models to characterize complex comorbidity patterns.

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Annexe

Additional resources

Bibliography

  1. Sonnenberg, F. A., & Beck, J. R. (1993). Markov models in medical decision making: A practical guide.
    Medical Decision Making: An International Journal of the Society for Medical Decision Making,
    13(4), 322–338. https://doi.org/10.1177/0272989X9301300409
  2. Wang, X., Sontag, D., & Wang, F. (2014). Unsupervised Learning of Disease Progression Models. Proceedings of the 20th ACM SIGKDD International Conference on Knowledge Discovery and Data Mining, 85–94. https://doi.org/10.1145/2623330.2623754
  3. P. Dworzynski, M. Aasbrenn, K. Rostgaard, M. Melbye, T. A. Gerds, H. Hjalgrim, and T. H. Pers. Nationwide prediction of type 2 diabetes comorbidities. Nature Scientific Report, vol. 10, 2019.
  4. M. Ravaut, H. Sadeghi, K. K. Leung, M. Volkovs, K. Kornas, V. Harish, T. Watson, G. F. Lewis, A. Weisman, T. Poutanen, and L. C. Rosella. Predicting adverse outcomes due to diabetes complications with machine learning using administrative health data.npj Digital Medicine, 4:1-12, 2021.

Publications

Faquetti, M. L.; La Torre, A. M.; Burkard, T.; Obozinski, G.; Burden, A. M. "Identification of polypharmacy patterns in new‐users of metformin using the Apriori algorithm: A novel framework for investigating concomitant drug utilization through association rule mining" Pharmacoepidemiology and Drug Safety 32 3 366-381 2023 View publication
Martinez-De La Torre, A.; Perez-Cruz, F.; Weiler, S.; Burden, A. M. "Comorbidity clusters associated with newly treated type 2 diabetes mellitus: a Bayesian nonparametric analysis" Scientific Reports 12 1 20653 2022 View publication

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