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Single-cell RNA sequencing (scRNA-seq) data simulation is limited by classical methods that rely on linear correlations, failing to capture the intrinsic, nonlinear dependencies. No existing simulator jointly models gene-gene and cell-cell interactions. We introduce qSimCells, a novel quantum computing-based simulator that employs entanglement to model intra- and inter-cellular interactions, generating realistic single-cell transcriptomes with cellular heterogeneity. The core innovation is a quantum kernel that uses a parameterized quantum circuit with CNOT gates to encode complex, nonlinear gene regulatory network (GRN) as well as cell-cell communication topologies with explicit causal directionality. The resulting synthetic data exhibits non-classical dependencies: standard correlation-based analyses (Pearson and Spearman) fail to recover the programmed causal pathways and instead report spurious associations driven by high baseline gene-expression probabilities. Furthermore, applying cell-cell communication detection to the simulated data validates the true mechanistic links, revealing a robust, up to 75-fold relative increase in inferred communication probability only when quantum entanglement is active. These results demonstrate that the quantum kernel is essential for producing high-fidelity ground-truth datasets and highlight the need for advanced inference techniques to capture the complex, non-classical dependencies inherent in gene regulation.

Advancements in artificial intelligence (AI) have transformed many scientific fields, with microbiology and microbiome research now experiencing significant breakthroughs through machine learning applications. This review provides a comprehensive overview of AI-driven approaches tailored for microbiology and microbiome studies, emphasizing both technical advancements and biological insights. We begin with an introduction to foundational AI techniques, including primary machine learning paradigms and various deep learning architectures, and offer guidance on choosing between traditional machine learning and sophisticated deep learning methods based on specific research goals. The primary section on application scenarios spans diverse research areas, from taxonomic profiling, functional annotation & prediction, microbe-X interactions, microbial ecology, metabolic modeling, precision nutrition, clinical microbiology, to prevention & therapeutics. Finally, we discuss challenges in this field and highlight some recent breakthroughs. Together, this review underscores AI's transformative role in microbiology and microbiome research, paving the way for innovative methodologies and applications that enhance our understanding of microbial life and its impact on our planet and our health.

Biological systems can form complex three-dimensional structures through the collective behavior of identical agents -- cells that follow the same internal rules and communicate without central control. How such distributed control gives rise to precise global patterns remains a central question not only in developmental biology but also in distributed robotics, programmable matter, and multi-agent learning. Here, we introduce DiffeoMorph, an end-to-end differentiable framework for learning a morphogenesis protocol that guides a population of agents to morph into a target 3D shape. Each agent updates its position and internal state using an attention-based SE(3)-equivariant graph neural network, based on its own internal state and signals received from other agents. To train this system, we introduce a new shape-matching loss based on the 3D Zernike polynomials, which compares the predicted and target shapes as continuous spatial distributions, not as discrete point clouds, and is invariant to agent ordering, number of agents, and rigid-body transformations. To enforce full SO(3) invariance -- invariant to rotations yet sensitive to reflections, we include an alignment step that optimally rotates the predicted Zernike spectrum to match the target before computing the loss. This results in a bilevel problem, with the inner loop optimizing a unit quaternion for the best alignment and the outer loop updating the agent model. We compute gradients through the alignment step using implicit differentiation. We perform systematic benchmarking to establish the advantages of our shape-matching loss over other standard distance metrics for shape comparison tasks. We then demonstrate that DiffeoMorph can form a range of shapes -- from simple ellipsoids to complex morphologies -- using only minimal spatial cues.

Cancer research is increasingly driven by the integration of diverse data modalities, spanning from genomics and proteomics to imaging and clinical factors. However, extracting actionable insights from these vast and heterogeneous datasets remains a key challenge. The rise of foundation models (FMs) -- large deep-learning models pretrained on extensive amounts of data serving as a backbone for a wide range of downstream tasks -- offers new avenues for discovering biomarkers, improving diagnosis, and personalizing treatment. This paper presents a comprehensive review of widely adopted integration strategies of multimodal data to assist advance the computational approaches for data-driven discoveries in oncology. We examine emerging trends in machine learning (ML) and deep learning (DL), including methodological frameworks, validation protocols, and open-source resources targeting cancer subtype classification, biomarker discovery, treatment guidance, and outcome prediction. This study also comprehensively covers the shift from traditional ML to FMs for multimodal integration. We present a holistic view of recent FMs advancements and challenges faced during the integration of multi-omics with advanced imaging data. We identify the state-of-the-art FMs, publicly available multi-modal repositories, and advanced tools and methods for data integration. We argue that current state-of-the-art integrative methods provide the essential groundwork for developing the next generation of large-scale, pre-trained models poised to further revolutionize oncology. To the best of our knowledge, this is the first review to systematically map the transition from conventional ML to advanced FM for multimodal data integration in oncology, while also framing these developments as foundational for the forthcoming era of large-scale AI models in cancer research.

In a mathematical model of interacting biological organisms, where external interventions may alter behavior over time, traditional models that assume fixed parameters usually do not capture the evolving dynamics. In oncology, this is further exacerbated by the fact that experimental data are often sparse and sometimes are composed of a few time points of tumor volume. In this paper, we propose to learn time-varying interactions between cells, such as those of bladder cancer tumors and immune cells, and their response to a combination of anticancer treatments in a limited data scenario. We employ the physics-informed neural network (PINN) approach to predict possible subpopulation trajectories at time points where no observed data are available. We demonstrate that our approach is consistent with the biological explanation of subpopulation trajectories. Our method provides a framework for learning evolving interactions among biological organisms when external interventions are applied to their environment.

Large language models (LLMs) are routinely used by physicians and patients for medical advice, yet their clinical safety profiles remain poorly characterized. We present NOHARM (Numerous Options Harm Assessment for Risk in Medicine), a benchmark using 100 real primary care-to-specialist consultation cases to measure frequency and severity of harm from LLM-generated medical recommendations. NOHARM covers 10 specialties, with 12,747 expert annotations for 4,249 clinical management options. Across 31 LLMs, potential for severe harm from LLM recommendations occurs in up to 22.2% (95% CI 21.6-22.8%) of cases, with harm of omission accounting for 76.6% (95% CI 76.4-76.8%) of errors. Safety performance is only moderately correlated (r = 0.61-0.64) with existing AI and medical knowledge benchmarks. The best models outperform generalist physicians on safety (mean difference 9.7%, 95% CI 7.0-12.5%), and a diverse multi-agent approach improves safety compared to solo models (mean difference 8.0%, 95% CI 4.0-12.1%). Therefore, despite strong performance on existing evaluations, widely used AI models can produce severely harmful medical advice at nontrivial rates, underscoring clinical safety as a distinct performance dimension necessitating explicit measurement.

Advanced nanopore measurements allow structural probing of molecules with high spatial and temporal resolution. We report high signal-to-noise, 1-10 MHz bandwidth, translocation measurements of the multi-state folding of heme protein cytochrome c in KCl solution through optimally designed silicon nitride pores of 2.3-3.3 nm diameter and 3.6-3.8 nm effective thickness, and an optimal concentration of a denaturant (Gdm-Cl). The pore diameter is slightly smaller than the protein size, forcing the protein to squeeze through the pore. The sufficiently large pore thickness allows enough time for protein probing at an applied field of approximately 250 kV/cm. Through Bayesian Information Criterion score analysis, current blockades reveal six distinct levels, attributed to specific protein states. We calculate the transition probabilities between the states and the conditional probabilities of the protein leaving the pore from each state. We validate the model by simulating events and comparing them to experimental data.

Sleep is essential for good health throughout our lives, yet studying its dynamics requires manual sleep staging, a labor-intensive step in sleep research and clinical care. Across centers, polysomnography (PSG) recordings are traditionally scored in 30-s epochs for pragmatic, not physiological, reasons and can vary considerably in electrode count, montage, and subject characteristics. These constraints present challenges in conducting harmonized multi-center sleep studies and discovering novel, robust biomarkers on shorter timescales. Here, we present AnySleep, a deep neural network model that uses any electroencephalography (EEG) or electrooculography (EOG) data to score sleep at adjustable temporal resolutions. We trained and validated the model on over 19,000 overnight recordings from 21 datasets collected across multiple clinics, spanning nearly 200,000 hours of EEG and EOG data, to promote robust generalization across sites. The model attains state-of-the-art performance and surpasses or equals established baselines at 30-s epochs. Performance improves as more channels are provided, yet remains strong when EOG is absent or when only EOG or single EEG derivations (frontal, central, or occipital) are available. On sub-30-s timescales, the model captures short wake intrusions consistent with arousals and improves prediction of physiological characteristics (age, sex) and pathophysiological conditions (sleep apnea), relative to standard 30-s scoring. We make the model publicly available to facilitate large-scale studies with heterogeneous electrode setups and to accelerate the discovery of novel biomarkers in sleep.

The purpose of this study is to enable in-vivo three-dimensional (3-D) ultrasound localization microscopy (ULM) of posterior ocular microvasculature using a 256-channel system and a 1024-element matrix array, and to overcome limitations of restricted transmit angles, sound speed mismatch caused by the crystalline lens and surrounding tissues, and the low signal-to-noise ratio (SNR) of microbubble signals. To address phase distortions from the crystalline lens, which has a higher speed of sound (SOS) than surrounding tissues, a region-dependent SOS beamforming approach was implemented to improve microbubble resolution. A 4-D non-local means filter was subsequently applied to suppress background noise and enhance microbubble contrast. The proposed method improved localization accuracy and image quality, achieving a spatial resolution of 63 um, while Fourier shell correlation (1/2-bit threshold) confirmed a global resolution of approximately 59 um. Higher mean normalized cross-correlation coefficients between the microbubbles and the system point-spread function, obtained with the proposed method (approximately 0.67), compared with those without the proposed method (approximately 0.60), indicate enhanced microbubble signal quality. Furthermore, the 3-D bi-directional vessel density and flow-velocity maps were reconstructed, capturing detailed choroidal vascular and hemodynamic patterns. These results demonstrate that region-dependent SOS beamforming combined with spatiotemporal denoising enables high-resolution posterior ocular ULM and provides a practical pathway toward quantitative 3-D assessment of retinal and choroidal microvasculature for potential clinical use.

Classical autoassociative memory models have been central to understanding emergent computations in recurrent neural circuits across diverse biological contexts. However, they typically neglect neuromodulatory agents that are known to strongly shape memory capacity and stability. Here we introduce a minimal, biophysically motivated associative memory network where neuropeptide-like signals are modeled by a self-adaptive, activity-dependent gating mechanism. Using many-body simulations and dynamical mean-field theory, we show that such gating fundamentally reorganizes the attractor structure: the network bypasses the classical spin-glass transition, maintaining robust, high-overlap retrieval far beyond the standard critical capacity, without shrinking basins of attraction. Mechanistically, the gate stabilizes transient "ghost" remnants of stored patterns even far above the Hopfield limit, converting them into multistable attractors. These results demonstrate that neuromodulation-like gating alone can dramatically enhance associative memory capacity, eliminate the sharp Hopfield-style catastrophic breakdown, and reshape the memory landscape, providing a simple, general route to richer memory dynamics and computational capabilities in neuromodulated circuits and neuromorphic architectures.