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With advances in high-throughput technology, molecular disease subtyping by high-dimensional omics data has been recognized as an effective approach for identifying subtypes of complex diseases with distinct disease mechanisms and prognoses. Conventional cluster analysis takes omics data as input and generates patient clusters with similar gene expression pattern. The omics data, however, usually contain multifaceted cluster structures that can be defined by different sets of genes. If the gene set associated with irrelevant clinical variables (e.g., sex or age) dominates the clustering process, the resulting clusters may not capture clinically meaningful disease subtypes. This motivates the development of a clustering framework with guidance from a prespecified disease outcome, such as lung function measurement or survival, in this paper. We propose two disease subtyping methods by omics data with outcome guidance using a generative model or a weighted joint likelihood. Both methods connect an outcome association model and a disease subtyping model by a latent variable of cluster labels. Compared to the generative model, weighted joint likelihood contains a data-driven weight parameter to balance the likelihood contributions from outcome association and gene cluster separation, which improves generalizability in independent validation but requires heavier computing. Extensive simulations and two real applications in lung disease and triple-negative breast cancer demonstrate superior disease subtyping performance of the outcome-guided clustering methods in terms of disease subtyping accuracy, gene selection and outcome association. Unlike existing clustering methods, the outcome-guided disease subtyping framework creates a new precision medicine paradigm to directly identify patient subgroups with clinical association.
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Temporal Clustering with External Memory Network for Disease Progression Modeling
We have developed a Temporal Clustering with External Memory Network (TC-EMNet) for disease progression modeling that groups patients with similar trajectories to form disease clusters/stages. Experiments on two real-world datasets show that our model demonstrates competitive clustering performance against state-of-the-art methods and is able to identify clinically meaningful clusters. The visualization of the extracted patient states shows that the proposed model can generate better patient states than the baselines.
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- Award ID(s):
- 2037398
- PAR ID:
- 10312658
- Date Published:
- Journal Name:
- Proceedings ICDM workshops
- ISSN:
- 2375-9259
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1109/ICDM51629.2021.00107
