Irving Institute for Cancer Dynamics
Researchers from New York Genome Center, NYU's Courant Institute, and Columbia University developed PerturbODE, an interpretable Neural ODE framework for inferring causal gene regulatory networks and dynamic cellular trajectories from large-scale single-cell perturbation data. This model accurately predicts the effects of unseen genetic interventions with a Pearson correlation of 0.67 and a W2 distance of 84, while also recovering biologically meaningful gene modules and outperforming existing causal discovery methods on the 817-gene TF Atlas dataset.
Disentangled representations enable models to separate factors of variation that are shared across experimental conditions from those that are condition-specific. This separation is essential in domains such as biomedical data analysis, where generalization to new treatments, patients, or species depends on isolating stable biological signals from context-dependent effects. While extensions of the variational autoencoder (VAE) framework have been proposed to address this problem, they frequently suffer from leakage between latent representations, limiting their ability to generalize to unseen conditions. Here, we introduce DISCoVeR, a new variational framework that explicitly separates condition-invariant and condition-specific factors. DISCoVeR integrates three key components: (i) a dual-latent architecture that models shared and specific factors separately; (ii) two parallel reconstructions that ensure both representations remain informative; and (iii) a novel max-min objective that encourages clean separation without relying on handcrafted priors, while making only minimal assumptions. Theoretically, we show that this objective maximizes data likelihood while promoting disentanglement, and that it admits a unique equilibrium. Empirically, we demonstrate that DISCoVeR achieves improved disentanglement on synthetic datasets, natural images, and single-cell RNA-seq data. Together, these results establish DISCoVeR as a principled approach for learning disentangled representations in multi-condition settings.
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Scalar Ollivier-Ricci Curvature (SORC), a new discrete measure for weighted graphs and point clouds, is introduced with formal proof of its convergence in probability to the scalar curvature of an underlying Riemannian manifold. This work from Columbia University provides the first theoretical guarantee for a discrete scalar curvature definition derived from Ollivier-Ricci curvature to reliably approximate its continuous counterpart.
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