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This paper proposes a differentiable conservation layer to model the finite RISC pool in gene editing, challenging standard interpretations of guide-off-target scores as independent occupancies. The authors audit archival data and find that while corrected thermodynamic affinities align with repression directions, the proposed coupling lacks added predictive value over baseline methods on held-out families. Ultimately, the study contributes a reusable operator for modeling competition constraints rather than delivering a new high-performance predictor.
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One pool, many targets: a conservation layer and what archival data can identify

arXiv3 min de cititArticolul și perspectiva sunt în engleză.

arXiv:2610.00445v1 Announce Type: new Abstract: Pairwise guide--transcript scores do not enforce conservation of a finite guide-loaded RISC pool when they are interpreted independently as occupancies. We formulate a differentiable scalar equilibrium layer: one conservation equation with a unique positive root and exact implicit gradients. It yields a redistribution theorem, a qualified high-resource limit, an analysis of the retrieval approximation, and a conditional rank-invariance result: within one construct at one dose, rankings by fractional occupancy cannot distinguish equilibrium from independent scoring. We therefore audit the two experiments that proposition leaves open, dose and cross-context, on archival off-target data. Corrected thermodynamic affinities associate weakly with measured repression in the direction a working predictor requires, but a paired permutation test and a construct-cluster bootstrap do not establish added predictive value from the coupling: what survives their differing permutation-null baselines is \GapNet{}, a descriptive \GapNetOverSE{} of the equilibrium association's cluster standard error. The dose fits are heterogeneous and frequently violate the model-implied exponent constraint, which is superlinear rather than sublinear, so these data do not identify the competition parameter. A saturable compression of the competitor set holds both accuracy targets on held-out guide families but is not faster at the size measured. The contribution is a reusable conservation operator and the experimental information needed to test it. The code for this study is available at https://github.com/shadi97kh/One-Pool-Many-Targets.

Abstract:Pairwise guide--transcript scores do not enforce conservation of a finite guide-loaded RISC pool when they are interpreted independently as occupancies. We formulate a differentiable scalar equilibrium layer: one conservation equation with a unique positive root and exact implicit gradients. It yields a redistribution theorem, a qualified high-resource limit, an analysis of the retrieval approximation, and a conditional rank-invariance result: within one construct at one dose, rankings by fractional occupancy cannot distinguish equilibrium from independent scoring. We therefore audit the two experiments that proposition leaves open, dose and cross-context, on archival off-target data. Corrected thermodynamic affinities associate weakly with measured repression in the direction a working predictor requires, but a paired permutation test and a construct-cluster bootstrap do not establish added predictive value from the coupling: what survives their differing permutation-null baselines is \GapNet{}, a descriptive \GapNetOverSE{} of the equilibrium association's cluster standard error. The dose fits are heterogeneous and frequently violate the model-implied exponent constraint, which is superlinear rather than sublinear, so these data do not identify the competition parameter. A saturable compression of the competitor set holds both accuracy targets on held-out guide families but is not faster at the size measured. The contribution is a reusable conservation operator and the experimental information needed to test it. The code for this study is available at this https URL.

Machine Learning (cs.LG)

arXiv:2610.00445 [cs.LG]

(or arXiv:2610.00445v1 [cs.LG] for this version)

https://doi.org/10.48550/arXiv.2610.00445 Focus to learn more arXiv-issued DOI via DataCite (pending registration)

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