Paper List
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Macroscopic Dominance from Microscopic Extremes: Symmetry Breaking in Spatial Competition
This paper addresses the fundamental question of how microscopic stochastic advantages in spatial exploration translate into macroscopic resource domi...
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Linear Readout of Neural Manifolds with Continuous Variables
This paper addresses the core challenge of quantifying how the geometric structure of high-dimensional neural population activity (neural manifolds) d...
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Theory of Cell Body Lensing and Phototaxis Sign Reversal in “Eyeless” Mutants of Chlamydomonas
This paper solves the core puzzle of how eyeless mutants of Chlamydomonas exhibit reversed phototaxis by quantitatively modeling the competition betwe...
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Cross-Species Transfer Learning for Electrophysiology-to-Transcriptomics Mapping in Cortical GABAergic Interneurons
This paper addresses the challenge of predicting transcriptomic identity from electrophysiological recordings in human cortical interneurons, where li...
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Uncovering statistical structure in large-scale neural activity with Restricted Boltzmann Machines
This paper addresses the core challenge of modeling large-scale neural population activity (1500-2000 neurons) with interpretable higher-order interac...
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Realizing Common Random Numbers: Event-Keyed Hashing for Causally Valid Stochastic Models
This paper addresses the critical problem that standard stateful PRNG implementations in agent-based models violate causal validity by making random d...
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A Standardized Framework for Evaluating Gene Expression Generative Models
This paper addresses the critical lack of standardized evaluation protocols for single-cell gene expression generative models, where inconsistent metr...
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Single Molecule Localization Microscopy Challenge: A Biologically Inspired Benchmark for Long-Sequence Modeling
This paper addresses the core challenge of evaluating state-space models on biologically realistic, sparse, and stochastic temporal processes, which a...
Probabilistic Joint and Individual Variation Explained (ProJIVE) for Data Integration
Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University | Department of Radiology and Imaging Sciences, Emory University School of Medicine
30秒速读
IN SHORT: This paper addresses the core challenge of accurately decomposing shared (joint) and dataset-specific (individual) sources of variation in multi-modal datasets, where existing methods often lack a formal statistical model, leading to potential inaccuracies and interpretability issues.
核心创新
- Methodology Introduces ProJIVE, a novel probabilistic model that extends Probabilistic PCA (pPCA) to the JIVE framework, formally modeling joint and individual subject scores as random effects.
- Methodology Develops a unified Expectation-Maximization (EM) algorithm for maximum likelihood estimation, simultaneously inferring all model parameters (loadings, scores, noise variances), unlike multi-step decomposition approaches.
- Biology Successfully applies the model to integrate brain morphometry and cognitive data from the ADNI cohort, demonstrating that the extracted joint scores strongly correlate with established but expensive Alzheimer's disease biomarkers (e.g., amyloid PET, FDG-PET, ApoE4 status).
主要结论
- ProJIVE's maximum likelihood estimation via EM achieved greater accuracy in estimating latent scores and variable loadings compared to R.JIVE, AJIVE, and GIPCA across various simulation settings, including non-Gaussian data.
- In the ADNI application, the joint subject scores derived from brain morphometry and cognition data showed strong statistical associations with key Alzheimer's disease variables, validating the biological relevance of the extracted shared variation.
- The model provides a formal statistical framework where quantities like joint subject scores (potential prodromes) and variable loadings (drivers of variation) are directly modeled, enhancing interpretability over algorithmic decompositions.
摘要: Collecting multiple types of data on the same set of subjects is common in modern scientific applications including genomics, metabolomics, and neuroimaging. Joint and Individual Variation Explained (JIVE) seeks a low-rank approximation of the joint variation between two or more sets of features captured on common subjects and isolates this variation from that unique to each set of features. We develop an expectation-maximization (EM) algorithm to estimate a probabilistic model for the JIVE framework. The model extends probabilistic PCA to multiple datasets. Our maximum likelihood approach simultaneously estimates joint and individual components, which can lead to greater accuracy compared to other methods. We apply ProJIVE to measures of brain morphometry and cognition in Alzheimer’s disease. ProJIVE learns biologically meaningful sources of variation, and the joint morphometry and cognition subject scores are strongly related to more expensive existing biomarkers. Data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. Code to reproduce the analysis is available at https://github.com/thebrisklab/ProJIVE. Supplementary materials for this article are available online.