MMIL: A novel algorithm for disease associated cell type discovery
This addresses the challenge of disease understanding and management in scenarios with unknown gold-standard labels and high dimensionality, particularly for diseases like AML and ALL, though it appears incremental as it builds on existing multiple instance learning methods.
The paper tackles the problem of identifying disease-associated cell types in single-cell datasets lacking individual cell labels by introducing Mixture Modeling for Multiple Instance Learning (MMIL), an expectation maximization method that trains cell-level classifiers using patient-level labels, achieving accurate identification of cancer cells in AML and ALL with generalization across tissues and treatment timepoints.
Single-cell datasets often lack individual cell labels, making it challenging to identify cells associated with disease. To address this, we introduce Mixture Modeling for Multiple Instance Learning (MMIL), an expectation maximization method that enables the training and calibration of cell-level classifiers using patient-level labels. Our approach can be used to train e.g. lasso logistic regression models, gradient boosted trees, and neural networks. When applied to clinically-annotated, primary patient samples in Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia (ALL), our method accurately identifies cancer cells, generalizes across tissues and treatment timepoints, and selects biologically relevant features. In addition, MMIL is capable of incorporating cell labels into model training when they are known, providing a powerful framework for leveraging both labeled and unlabeled data simultaneously. Mixture Modeling for MIL offers a novel approach for cell classification, with significant potential to advance disease understanding and management, especially in scenarios with unknown gold-standard labels and high dimensionality.