Shesha quantifies directional coherence of single-cell CRISPR responses, correlates strongly with effect magnitude, distinguishes pleiotropic from lineage-specific regulators, and predicts chaperone activation after magnitude correction.
Geometric Stability: The Missing Axis of Representations
3 Pith papers cite this work. Polarity classification is still indexing.
abstract
Representational similarity analysis and related methods have become standard tools for comparing the internal geometries of neural networks and biological systems. These methods measure what is represented, the alignment between two representational spaces, but not whether that structure is robust. We introduce geometric stability, a distinct dimension of representational quality that quantifies how reliably a representation's pairwise distance structure holds under perturbation. Our metric, Shesha, measures self-consistency through split-half correlation of representational dissimilarity matrices constructed from complementary feature subsets. A key formal property distinguishes stability from similarity: Shesha is not invariant to orthogonal transformations of the feature space, unlike CKA and Procrustes, enabling it to detect compression-induced damage to manifold structure that similarity metrics cannot see. Spectral analysis reveals the mechanism: similarity metrics collapse after removing the top principal component, while stability retains sensitivity across the eigenspectrum. Across 2463 encoder configurations in seven domains -- language, vision, audio, video, protein sequences, molecular profiles, and neural population recordings -- stability and similarity are empirically uncorrelated ($\rho=-0.01$). A regime analysis shows this independence arises from opposing effects: geometry-preserving transformations make the metrics redundant, while compression makes them anti-correlated, canceling in aggregate. Applied to 94 pretrained models across 6 datasets, stability exposes a "geometric tax": DINOv2, the top-performing model for transfer learning, ranks last in geometric stability on 5/6 datasets. Contrastive alignment and hierarchical architecture predict stability, providing actionable guidance for model selection in deployment contexts where representational reliability matters.
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2026 3verdicts
UNVERDICTED 3roles
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unclear 1representative citing papers
Discrete tokenization in scientific foundation models imposes a geometric alignment tax that distorts continuous manifolds, with continuous heads reducing distortion by up to 8.5x and exposing three failure regimes in 14 biological models.
Geometric stability, defined as the directional coherence of cellular responses to perturbation, provides a framework for assessing whether resulting cellular states are stable beyond conventional metrics of intervention success.
citing papers explorer
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Geometric coherence of single-cell CRISPR perturbations reveals regulatory architecture and predicts cellular stress
Shesha quantifies directional coherence of single-cell CRISPR responses, correlates strongly with effect magnitude, distinguishes pleiotropic from lineage-specific regulators, and predicts chaperone activation after magnitude correction.
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The Geometric Alignment Tax: Tokenization vs. Continuous Geometry in Scientific Foundation Models
Discrete tokenization in scientific foundation models imposes a geometric alignment tax that distorts continuous manifolds, with continuous heads reducing distortion by up to 8.5x and exposing three failure regimes in 14 biological models.
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From Syntax to Semantics: Geometric Stability as the Missing Axis of Perturbation Biology
Geometric stability, defined as the directional coherence of cellular responses to perturbation, provides a framework for assessing whether resulting cellular states are stable beyond conventional metrics of intervention success.