Leukemia
Profile Graphical Models
Avalos-Pacheco, Alejandra, Lupparelli, Monia, Stingo, Francesco C.
We introduce a novel class of graphical models, termed profile graphical models, that represent, within a single graph, how an external factor influences the dependence structure of a multivariate set of variables. This class is quite general and includes multiple graphs and chain graphs as special cases. Profile graphical models capture the conditional distributions of a multivariate random vector given different levels of a risk factor, and learn how the conditional independence structure among variables may vary across these risk profiles; we formally define this family of models and establish their corresponding Markov properties. We derive key structural and probabilistic properties that underpin a more powerful inferential framework than existing approaches, underscoring that our contribution extends beyond a novel graphical representation.Furthermore, we show that the resulting profile undirected graphical models are independence-compatible with two-block LWF chain graph models.We then develop a Bayesian approach for Gaussian undirected profile graphical models based on continuous spike-and-slab priors to learn shared sparsity structures across different levels of the risk factor. We also design a fast EM algorithm for efficient inference. Inferential properties are explored through simulation studies, including the comparison with competing methods. The practical utility of this class of models is demonstrated through the analysis of protein network data from various subtypes of acute myeloid leukemia. Our results show a more parsimonious network and greater patient heterogeneity than its competitors, highlighting its enhanced ability to capture subject-specific differences.
Manifold Interpolating Optimal-Transport Flows for Trajectory Inference
We present a method called Manifold Interpolating Optimal-Transport Flow (MIOFlow) that learns stochastic, continuous population dynamics from static snapshot samples taken at sporadic timepoints. MIOFlow combines dynamic models, manifold learning, and optimal transport by training neural ordinary differential equations (Neural ODE) to interpolate between static population snapshots as penalized by optimal transport with manifold ground distance. Further, we ensure that the flow follows the geometry by operating in the latent space of an autoencoder that we call a geodesic autoencoder (GAE). In GAE the latent space distance between points is regularized to match a novel multiscale geodesic distance on the data manifold that we define. We show that this method is superior to normalizing flows, Schr\odinger bridges and other generative models that are designed to flow from noise to data in terms of interpolating between populations. Theoretically, we link these trajectories with dynamic optimal transport. We evaluate our method on simulated data with bifurcations and merges, as well as scRNA-seq data from embryoid body differentiation, and acute myeloid leukemia treatment.
Pioneering new treatment reverses incurable blood cancer in some patients
A therapy that would once have been considered a feat of science fiction has reversed aggressive and incurable blood cancers in some patients, doctors report. The treatment involves precisely editing the DNA in white blood cells to transform them into a cancer-fighting living drug. The first girl to be treated, whose story we reported in 2022, is still free of the disease and now plans to become a cancer scientist. Now eight more children and two adults with T-cell acute lymphoblastic leukaemia have been treated, with almost two thirds (64%) of patients in remission. T-cells are supposed to be the body's guardians - seeking out and destroying threats - but in this form of leukaemia, they grow out of control.
ADNF-Clustering: An Adaptive and Dynamic Neuro-Fuzzy Clustering for Leukemia Prediction
Aruta, Marco, Listone, Ciro, Murano, Giuseppe, Murano, Aniello
Leukemia diagnosis and monitoring rely increasingly on high-throughput image data, yet conventional clustering methods lack the flexibility to accommodate evolving cellular patterns and quantify uncertainty in real time. We introduce Adaptive and Dynamic Neuro-Fuzzy Clustering, a novel streaming-capable framework that combines Convolutional Neural Network-based feature extraction with an online fuzzy clustering engine. ADNF initializes soft partitions via Fuzzy C-Means, then continuously updates micro-cluster centers, densities, and fuzziness parameters using a Fuzzy Temporal Index (FTI) that measures entropy evolution. A topology refinement stage performs density-weighted merging and entropy-guided splitting to guard against over- and under-segmentation. On the C-NMC leukemia microscopy dataset, our tool achieves a silhouette score of 0.51, demonstrating superior cohesion and separation over static baselines. The method's adaptive uncertainty modeling and label-free operation hold immediate potential for integration within the INFANT pediatric oncology network, enabling scalable, up-to-date support for personalized leukemia management.
Non-Negative Stiefel Approximating Flow: Orthogonalish Matrix Optimization for Interpretable Embeddings
Avants, Brian B., Tustison, Nicholas J., Stone, James R
Interpretable representation learning is a central challenge in modern machine learning, particularly in high-dimensional settings such as neuroimaging, genomics, and text analysis. Current methods often struggle to balance the competing demands of interpretability and model flexibility, limiting their effectiveness in extracting meaningful insights from complex data. We introduce Non-negative Stiefel Approximating Flow (NSA-Flow), a general-purpose matrix estimation framework that unifies ideas from sparse matrix factorization, orthogonalization, and constrained manifold learning. NSA-Flow enforces structured sparsity through a continuous balance between reconstruction fidelity and column-wise decorrelation, parameterized by a single tunable weight. The method operates as a smooth flow near the Stiefel manifold with proximal updates for non-negativity and adaptive gradient control, yielding representations that are simultaneously sparse, stable, and interpretable. Unlike classical regularization schemes, NSA-Flow provides an intuitive geometric mechanism for manipulating sparsity at the level of global structure while simplifying latent features. We demonstrate that the NSA-Flow objective can be optimized smoothly and integrates seamlessly with existing pipelines for dimensionality reduction while improving interpretability and generalization in both simulated and real biomedical data. Empirical validation on the Golub leukemia dataset and in Alzheimer's disease demonstrate that the NSA-Flow constraints can maintain or improve performance over related methods with little additional methodological effort. NSA-Flow offers a scalable, general-purpose tool for interpretable ML, applicable across data science domains.
Penalized Empirical Likelihood for Doubly Robust Causal Inference under Contamination in High Dimensions
Lee, Byeonghee, Kang, Sangwook, Park, Ju-Hyun, Jeon, Saebom, Kang, Joonsung
We propose a doubly robust estimator for the average treatment effect in high dimensional low sample size observational studies, where contamination and model misspecification pose serious inferential challenges. The estimator combines bounded influence estimating equations for outcome modeling with covariate balancing propensity scores for treatment assignment, embedded within a penalized empirical likelihood framework using nonconvex regularization. It satisfies the oracle property by jointly achieving consistency under partial model correct ness, selection consistency, robustness to contamination, and asymptotic normality. For uncertainty quantification, we derive a finite sample confidence interval using cumulant generating functions and influence function corrections, avoiding reliance on asymptotic approximations. Simulation studies and applications to gene expression datasets (Golub and Khan) demonstrate superior performance in bias, error metrics, and interval calibration, highlighting the method robustness and inferential validity in HDLSS regimes. One notable aspect is that even in the absence of contamination, the proposed estimator and its confidence interval remain efficient compared to those of competing models.