Single-cell multiomics reveals a gene regulatory circuit driving leukemia cell differentiation
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Latent circuit inference from heterogeneous neural responses during cognitive tasks
Higher cortical areas carry a wide range of sensory, cognitive and motor signals mixed in heterogeneous responses of single neurons tuned to multiple task variables. Dimensionality reduction methods that rely on correlations between neural activity and task variables leave unknown how heterogeneous responses arise from connectivity to drive behavior. We develop the latent circuit model, a dimensionality reduction approach in which task variables interact via low-dimensional recurrent connectivity to produce behavioral output. We apply the latent circuit inference to recurrent neural networks trained to perform a context-dependent decision-making task and find a suppression mechanism in which contextual representations inhibit irrelevant sensory responses. We validate this mechanism by confirming the behavioral effects of patterned connectivity perturbations predicted by the latent circuit model. We find similar suppression of irrelevant sensory responses in the prefrontal cortex of monkeys performing the same task. We show that incorporating causal interactions among task variables is critical for identifying behaviorally relevant computations from neural response data.
Enhancer reprogramming: critical roles in cancer and promising therapeutic strategies
Transcriptional dysregulation is a hallmark of cancer initiation and progression, driven by genetic and epigenetic alterations. Enhancer reprogramming has emerged as a pivotal driver of carcinogenesis, with cancer cells often relying on aberrant transcriptional programs. The advent of high-throughput sequencing technologies has provided critical insights into enhancer reprogramming events and their role in malignancy. While targeting enhancers presents a promising therapeutic strategy, significant challenges remain. These include the off-target effects of enhancer-targeting technologies, the complexity and redundancy of enhancer networks, and the dynamic nature of enhancer reprogramming, which may contribute to therapeutic resistance. This review comprehensively encapsulates the structural attributes of enhancers, delineates the mechanisms underlying their dysregulation in malignant transformation, and evaluates the therapeutic opportunities and limitations associated with targeting enhancers in cancer.
A system-level model reveals that transcriptional stochasticity is required for hematopoietic stem cell differentiation
HSCs differentiation has been difficult to study experimentally due to the high number of components and interactions involved, as well as the impact of diverse physiological conditions. From a 200-node network, that was grounded on experimental data, we derived a 21-node regulatory network by collapsing linear pathways and retaining the functional feedback loops. This regulatory network core integrates key nodes and interactions underlying HSCs differentiation, including transcription factors, metabolic, and redox signaling pathways. We used Boolean, continuous, and stochastic dynamic models to simulate the hypoxic conditions of the HSCs niche, as well as the patterns and temporal sequences of HSCs transitions and differentiation. Our findings indicate that HSCs differentiation is a plastic process in which cell fates can transdifferentiate among themselves. Additionally, we found that cell heterogeneity is fundamental for HSCs differentiation. Lastly, we found that oxygen activates ROS production, inhibiting quiescence and promoting growth and differentiation pathways of HSCs.
Parallel circuit implementation of variational quantum algorithms
We present a framework to split quantum circuits of variational quantum algorithms (VQAs) to allow for parallel training and execution to solve problems larger than the number of available qubits in a quantum device. We apply this method to combinatorial optimization problems, where inherent structures can be identified, and show how to implement these parallelized quantum circuits. We show how to formulate an objective function for the classical optimizer to guide the optimization towards meaningful solutions. We test our framework by creating a parallelized version of the Quantum Approximate Optimization Algorithm and a variational version of quantum annealing and explain how our framework applies to other quantum optimization algorithms. We provide results obtained both from simulation and experiments on real hardware. Our results show that the information lost by splitting the quantum circuits can be partially recovered by optimizing a global objective function evaluated with the separate circuit samples.
Connecting physics to systems with modular spin-circuits
An emerging paradigm in modern electronics is that of CMOS+ ({mathsf{X}}) requiring the integration of standard CMOS technology with novel materials and technologies denoted by ({mathsf{X}}). In this context, a crucial challenge is to develop accurate circuit models for ({mathsf{X}}) that are compatible with standard models for CMOS-based circuits and systems. In this perspective, we present physics-based, experimentally benchmarked modular circuit models that can be used to evaluate a class of CMOS+ ({mathsf{X}}) systems, where ({mathsf{X}}) denotes magnetic and spintronic materials and phenomena. This class of materials is particularly challenging because they go beyond conventional charge-based phenomena and involve the spin degree of freedom which involves non-trivial quantum effects. Starting from density matrices—the central quantity in quantum transport—using well-defined approximations, it is possible to obtain spin-circuits that generalize ordinary circuit theory to 4-component currents and voltages (1 for charge and 3 for spin). With step-by-step examples that progressively become more complex, we illustrate how the spin-circuit approach can be used to start from the physics of magnetism and spintronics to enable accurate system-level evaluations. We believe the core approach can be extended to include other quantum degrees of freedom like valley and pseudospins starting from corresponding density matrices.
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