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Single-cell (sc)RNA-seq, together with RNA velocity and metabolic labeling, reveals cellular states and transitions at unprecedented resolution. Fully exploiting these data, however, requires kinetic models capable of unveiling governing regulatory functions. Here, we introduce an analytical framework dynamo (https://github.com/aristoteleo/dynamo-release), which infers absolute RNA velocity, reconstructs continuous vector fields that predict cell fates, employs differential geometry to extract underlying regulations, and ultimately predicts optimal reprogramming paths and perturbation outcomes. We highlight dynamo’s power to overcome fundamental limitations of conventional splicing-based RNA velocity analyses to enable accurate velocity estimations on a metabolically labeled human hematopoiesis scRNA-seq dataset. Furthermore, differential geometry analyses reveal mechanisms driving early megakaryocyte appearance and elucidate asymmetrical regulation within the PU.1-GATA1 circuit. Leveraging the least-action-path method, dynamo accurately predicts drivers of numerous hematopoietic transitions. Finally, in silico perturbations predict cell-fate diversions induced by gene perturbations. Dynamo, thus, represents an important step in advancing quantitative and predictive theories of cell-state transitions.

This article considers experimental design based on the strategy of rerandomization to increase the efficiency in experiments. Two aspects of rerandomization are addressed. First, we propose a two-stage allocation sample scheme for randomization inference to the units in experiments that guarantees that the difference-in-mean estimator is an unbiased estimator of the sample average treatment effect for any experiment, conserves the exactness of randomization inference, and halves the time consumption of the rerandomization design. Second, we propose a rank-based covariate-balance measure which can take into account the estimated relative weight of each covariate. Several strategies for estimating these weights using pre-experimental data are proposed. Using Monte Carlo simulations, the proposed strategies are compared to complete randomization and Mahalanobis-based rerandomization. An empirical example is given where the power of a mean difference test of electricity consumption of 54 households is increased by 99%, in comparison to complete randomization, using one of the proposed designs based on high frequency longitudinal electricity consumption data. Supplementary materials for this article are available online.

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Mirror symmetry conjecture identifies the complex geometry of a Calabi $ Yau manifold with the symplectic geometry of its mirror Calabi $ Yau man $ ifold. Using the SYZ mirror transform, we argue that (i) the mirror of an elliptic Calabi $ Yau manifold admits a twin Lagrangian fibration structure and (ii) the mirror of the Fourier $ Mukai transform for dual elliptic fibra $ tions is a symplectic Fourier $ Mukai transform for dual twin Lagrangian fibrations, which is essentially an identity transformation in this case.