Academic Intelligence · Curated Daily

Explore the Frontier of Global Academia

AcademicHub aggregates real-time literature from top journals and preprint platforms. Build your personal research radar and let large language models compile cross-disciplinary analysis briefings automatically.

01.
arXiv (CS.AI) 2026-06-18

Efficient Zeroth-Order Federated Finetuning of Language Models on Resource-Constrained Devices

arXiv:2502.10239v3 Announce Type: replace-cross Abstract: Federated Learning (FL) is a promising paradigm for finetuning Large Language Models (LLMs) across distributed data sources while preserving data privacy. However, finetuning such large models is challenging on edge devices due to its high resource demand. Zeroth-order Optimization (ZO) estimates gradients through finite-difference approximations, which rely on function evaluations under random perturbations of the model parameters. Consequently, ZO with task alignment provides a potential solution, allowing finetuning using only forward passes with inference-level memory requirements and low communication overhead, but it suffers from slow convergence and higher computational demand. In this paper, we propose a new ZO-based method that applies a more efficient technique to reduce the computational demand associated with using a large number of perturbations while preserving their convergence benefits. This is achieved by splitting the model into consecutive blocks and allocating a higher number of perturbations to the second block, enabling efficient reuse of intermediate activations to update the full network with fewer forward evaluations. Our evaluation on RoBERTa-large, OPT1.3B, LLaMa-3-3.2B models shows up to $3\times$ reduction in computation compared to the other ZO-based techniques, while retaining the memory and communication benefits over first-order federated learning techniques.

02.
arXiv (CS.CV) 2026-06-17

Recover Semantics First, Generate Better: Improved Latent Modeling for 3D MRI Reconstruction and Cross-Contrast Synthesis

Multi-contrast magnetic resonance imaging (MRI) provides complementary information for clinical diagnosis. However, acquiring all MRI sequences is often time-consuming and costly. Recent generative models perform cross-contrast synthesis to address this issue by inferring absent contrasts from the available ones. Nevertheless, synthesizing 3D MRI presents significant challenges. Due to the massive volume sizes, operating directly in the pixel space is computationally prohibitive; therefore, a common approach is to first compress the 3D volumes into a latent space and subsequently train generative models in that space. We observe that existing compression architectures face several critical issues: they under-preserve long-range anatomical coherence, discard clinically meaningful semantics, and rely on optimization objectives that lead to over-smoothed reconstructions. Ultimately, these shortcomings compromise the performance of subsequent generative models. In this work, we propose a semantics-first latent modeling framework for 3D MRI reconstruction and cross-contrast synthesis. Specifically, we introduce a Latent Harmonization Encoder (LHE) to capture global anatomical dependencies, ensuring coherent volumetric representations. To mitigate semantic degradation during latent compression, we further design a Semantic Recovery Block (SRB) that injects high-level priors from a self-supervised semantic teacher, enhancing contrast-aware separability in the latent space. Additionally, we propose an Anatomy-aware Frequency Loss (AFL) to adaptively preserve diagnostically relevant high-frequency structures. Extensive experiments on two public multi-contrast MRI datasets demonstrate consistent improvements in reconstruction fidelity and cross-contrast synthesis quality. Our code is available at https://github.com/script-Yang/RSF.

03.
arXiv (math.PR) 2026-06-18

Stability of Khintchine-type inequalities via log-monotonicity

arXiv:2606.19313v1 Announce Type: new Abstract: We investigate Khintchine-type inequalities for the weighted sums $S=\sum_ka_kX_k$ of independent copies of a symmetric random variable $X$. We show how log-monotonicity of the sequence $r_k(X)=k! \mathbb{E}[X^{2k}]/(2k)!$ implies sharp comparisons between the $L_p$ and $L_2$ norms of $S$ for every even integer $p\geq 2$, extending classic Khintchine-type inequalities and yielding new results in the log-convex setting. We also investigate the stability of our inequalities. Our first stability inequality sharpens the classic inequality by a deviation of the coefficient vector from the coordinate extremizers, while the second quantifies deviation from the Gaussian limit. Our results recover recent stability inequalities for random signs and apply to a broad class of distributions, including type-$\mathscr{L}$ random variables, ultra sub-Gaussian random variables and Gaussian mixtures.

04.
arXiv (CS.AI) 2026-06-12

A Study of Belief Revision Postulates in Multi-Agent Systems (Extended Version)

arXiv:2605.02249v2 Announce Type: replace Abstract: We investigate the belief revision problem in epistemic planning, i.e., what will be the beliefs of all agents in a multi-agent system after an agent gains the belief in some state property. Based on the standard representation in epistemic planning of agents' beliefs via a single multi-agent Kripke model, we generalize the classical AGM belief revision postulates to the multi-agent setting, with the aim to provide a formal framework for evaluating dynamic epistemic reasoning frameworks in which the beliefs of all agents as the result of actions are computed. As an example of a simple operator that satisfies all of the generalized AGM postulates, we present generalized full-meet multi-agent belief revision. We moreover define a generalization of the standard postulates for iterated revision, present a more sophisticated, event model based revision operator, and discuss the potential issues in defining an epistemic operator on Kripke models that can satisfy all of the generalized postulates for iterated multi-agent belief revision.

05.
arXiv (CS.CV) 2026-06-15

Toward 360-Degree Indoor Panorama Editing via Tuning-Free Diffusion Model with Refocusing Cross-Attention

Zero-shot text-guided diffusion has significantly advanced image editing; however, its practical usability remains constrained by three persistent challenges: prompt brittleness that requires meticulous prompt engineering, spillover edits that unintentionally affect non-target regions, and failures on small or cluttered objects caused by limited fine-grained supervision in training data. We propose FocusDiff (Target-Aware Refocusing for Tuning-Free Diffusion Editing), a tuning-free framework for precise and region-specific image manipulation based on refocusing cross-attention. Given a target region obtained through automated segmentation or manual selection, FocusDiff applies selective blurring to non-edit areas to guide attention toward the masked region while accurately transferring the object's identity, structure, and appearance to the edited output. Integrated context-preserving modules further ensure background fidelity and global coherence, enabling accurate edits from simple text prompts in a single pass. We also extend FocusDiff to 360-degree indoor panorama editing and demonstrate its effectiveness within virtual reality environments. Extensive experiments on our localized editing benchmark LIMB, comprising 30 multi-object images and 100 annotated examples including challenging small-object cases, show that FocusDiff outperforms existing zero-shot editors in text-image alignment and background preservation, achieving superior precision, photorealism, and usability. The project page is available at https://vdkhoi20.github.io/FocusDiff.

06.
bioRxiv (Bioinfo) 2026-06-11

SPARK: A Systems-level Computational Framework for Reconstructing Transcriptomic State Organisation in Lung Adenocarcinoma

Lung adenocarcinoma (LUAD) exhibits substantial molecular heterogeneity, which complicates tumour stratification and limits the ability of mutation-centric models to capture tumour behaviour and predict patient outcomes. This study investigates whether coordinated transcriptomic programs can provide a systems-level representation of tumour states. Bulk RNA-sequencing data from the TCGA-LUAD cohort were analysed to reconstruct pathway-level transcriptomic organisation using a stability-optimised network framework (SPARK). This analysis identified eight transcriptomic modules representing coordinated biological processes active across tumours. Module activity scores were subsequently used to derive a composite Transcriptomic Risk Score through elastic-net Cox proportional hazards modelling. The resulting risk score showed a significant association with overall survival in the discovery cohort and improved prognostic discrimination beyond clinical variables. An independent evaluation in the CPTAC-LUAD cohort confirmed the prognostic signal and preserved risk stratification across patient groups. Unsupervised clustering of module activity further revealed three transcriptomic patient groups characterised by distinct biological programs, genomic alteration patterns, and survival outcomes. Single-cell analysis also demonstrated that the identified transcriptomic modules reflect coordinated organisation of the tumour-immune-stromal ecosystem across cellular compartments. Together, these findings suggest that LUAD heterogeneity can be organised into coordinated transcriptomic programs with measurable clinical relevance, providing a systems-level framework for representing tumour molecular states.

08.
arXiv (CS.CL) 2026-06-16

From Awareness to Adherence: Bridging the Context Gap in Spoken Dialogue Systems via Context-Aware Decoding

Despite the success of end-to-end (E2E) spoken dialogue systems, maintaining strict context adherence in multi-round conversations remains a challenge. While prior works attribute these failures to models forgetting dialogue history, we highlight an equally critical but overlooked bottleneck: a gap between latent context awareness and active adherence. Although models internally recognize relevant past utterances, strong parametric priors often overshadow these signals during decoding. To bridge this gap, we propose an audio-adapted Context-Aware Decoding (CAD) approach. By leveraging internal attention mechanisms to isolate key historical rounds, our approach contrasts output distributions with and without this key context during inference, directly amplifying multimodal contextual signals. Evaluations on the Audio MultiChallenge benchmark demonstrate significant improvements in Semantic Memory and Self Coherence subtasks, successfully enforcing strict, context-faithful adherence.

09.
arXiv (CS.LG) 2026-06-12

ResidualPlanner+: a scalable matrix mechanism for marginals and beyond

arXiv:2305.08175v5 Announce Type: replace-cross Abstract: Noisy marginals are a common form of confidentiality protecting data release and are useful for many downstream tasks such as contingency table analysis, construction of Bayesian networks, and even synthetic data generation. Privacy mechanisms that provide unbiased noisy answers to linear queries (such as marginals) are known as matrix mechanisms. We propose ResidualPlanner and ResidualPlanner+, two highly scalable matrix mechanisms. ResidualPlanner is both optimal and scalable for answering marginal queries with Gaussian noise, while ResidualPlanner+ provides support for more general workloads, such as combinations of marginals and range queries or prefix-sum queries. ResidualPlanner can optimize for many loss functions that can be written as a convex function of marginal variances (prior work was restricted to just one predefined objective function). ResidualPlanner can optimize the accuracy of marginals in large scale settings in seconds, even when the previous state of the art (HDMM) runs out of memory. It even runs on datasets with 100 attributes in a couple of minutes. Furthermore, ResidualPlanner can efficiently compute variance/covariance values for each marginal (prior methods quickly run out of memory, even for relatively small datasets). ResidualPlanner+ provides support for more complex workloads that combine marginal and range/prefix-sum queries (e.g., a marginal on race, a range query on age, and a combined race/age tabulation that answers age range queries for each race). It even supports custom user-defined workloads on different attributes. With this added flexibility, ResidualPlanner+ is not necessarily optimal, however it is still extremely scalable and outperforms the prior state-of-the-art (HDMM) on prefix-sum queries both in terms of accuracy and speed.

10.
arXiv (CS.CV) 2026-06-16

An Empirical Analysis of Optimization Dynamics and Sparsity Boundaries in Large-Scale Pedestrian Attribute Recognition

Pedestrian Attribute Recognition (PAR) is critical for video surveillance, enabling forensic search and re-identification systems. Extreme class imbalance remains a fundamental obstacle when merging PETA and PA-100K into a 109,000-image composite corpus, where minority attributes have positive sample fractions below 1%. This causes standard BCE optimization to suppress rare traits, a phenomenon we term the majority negative class cheating trap. We present a systematic ablation of Multi-Label Focal Loss hyperparameters (alpha and gamma) on a ResNet-18 backbone. A calibrated configuration (alpha=0.50, gamma=2.0) achieves a Macro F1-score of 62.32%, matching BCE baseline while preserving superior hard-example mining and convergence dynamics. Our approach uses pure loss-function engineering with zero computational overhead for edge deployment. We identify the Sparsity Wall, a hard boundary where positive sample fractions below 0.1% make global loss reweighting ineffective, requiring instance-level intervention.

11.
arXiv (CS.AI) 2026-06-11

A New Perspective on Precision and Recall for Generative Models

arXiv:2511.02414v3 Announce Type: replace Abstract: With the recent success of generative models in image and text, the question of their evaluation has recently gained a lot of attention. While most methods from the state of the art rely on scalar metrics, the introduction of Precision and Recall (PR) for generative model has opened up a new avenue of research. The associated PR curve allows for a richer analysis, but their estimation poses several challenges. In this paper, we present a new framework for estimating entire PR curves based on a binary classification standpoint. We conduct a thorough statistical analysis of the proposed estimates. As a byproduct, we obtain a minimax upper bound on the PR estimation risk. We also show that our framework extends several landmark PR metrics of the literature which by design are restrained to the extreme values of the curve. Finally, we study the different behaviors of the curves obtained experimentally in various settings.

12.
arXiv (CS.AI) 2026-06-16

The Integrator Advantage: Controlled Agentic AI for Small and Medium-Sized Companies

arXiv:2606.16649v1 Announce Type: new Abstract: Agentic AI marks a new phase of enterprise automation. Unlike traditional automation or conversational AI, agentic systems can interpret goals, plan multi step tasks, access tools, interact with enterprise systems, and execute workflows with varying degrees of autonomy. For small and medium sized companies, this creates potential to reduce administrative burden, accelerate routine processes, and improve the use of organizational knowledge. This paper argues that the near term value of Agentic AI does not lie in full autonomy or workforce reduction, but in controlled partial autonomy for simple and medium complexity business processes. It proposes an integration framework covering use case suitability, autonomy levels, technical integration, governance, security, employee enablement, and measurable impact. The paper concludes that Agentic AI can become a productivity lever when implemented as a human centered capability with responsibility and accountability retained by people.

13.
arXiv (CS.AI) 2026-06-17

Transformer-Based Warm-Starting for Feasible and Optimal Terminal Approach to Tumbling Objects with Space Manipulators

arXiv:2606.17317v1 Announce Type: cross Abstract: Real-time trajectory generation for on-orbit robotic servicing is challenging due to the nonlinear coupling between spacecraft bus motion, manipulator dynamics, visibility cone, and trajectory-level safety constraints. This paper studies learning-based warm-starting for sequential convex programming (SCP) in the terminal approach of a space manipulator toward a tumbling target. The proposed framework decomposes the problem into a system center-of-mass translational planning stage and a coupled attitude–manipulator torque-allocation stage, and applies a causal transformer warm-start to the latter, which constitutes the dominant computational bottleneck. Linear and flow matching action decoders are compared under different action-chunking and training dataset sizes, and the resulting warm-starts are evaluated under both cost-optimal and feasibility projection using SCP. Across 300 held-out scenarios, the learned warm-start reduces the second-stage SCP iteration count by up to 28% and the runtime by 23% while preserving the final control-cost distribution. When the learned warm-starts are used for nonconvex feasibility projection, they nearly halve the runtime relative to cost-optimal SCP, while avoiding the catastrophic high-cost tail behavior observed when initialized heuristically. These results indicate that sequence-model warm-starts can improve both the computational efficiency and trajectory robustness of optimization-based terminal guidance for space manipulation.

14.
arXiv (CS.CV) 2026-06-18

Rethinking the Pointer Loss in Table Structure Recognition: Geometry-Aware Pointer Loss for Spatial Locality

Table Structure Recognition (TSR) using a pointer network achieves impressive results by predicting HTML sequences while aligning tags to detected text (or cell) regions. However, our analysis reveals that when pointer networks fail, 79.6% of errors occur between spatially adjacent cells (Manhattan distance

15.
arXiv (math.PR) 2026-06-15

On the Poisson Follower Model

arXiv:2309.04864v5 Announce Type: replace Abstract: We introduce a stochastic geometry dynamics inspired by opinion dynamics that captures the essence of modern asymmetric social networks with leaders and followers. Points in the Euclidean space represent opinions, and the leader of an agent is the one with the closest opinion. In this dynamics, each follower updates its opinion by halving the distance to its leader. We demonstrate that this simple dynamics and its iterations exhibit several interesting purely geometric phenomena related to the evolution of leadership and opinion clusters, which resemble those observed in social networks. We also show that when the initial opinions are randomly distributed as a stationary Poisson point process, the spatial frequency of each of these phenomena can be expressed through an integral geometry formula involving semi-algebraic domains. Finally, we analyze numerically the limiting behavior of this follower dynamics. In the Poisson case, the agents fall into two categories: ultimate followers, who continue updating their opinions indefinitely, and ultimate leaders, who adopt a fixed opinion after a finite time. Spatial discrete event simulations support all our findings.

16.
arXiv (CS.CL) 2026-06-15

Abstracting Cross-Domain Action Sequences into Interpretable Workflows

Sequential or time-stamped interaction logs provide objective records of digital application usage, yet their granularity and noise often obscure meaningful insights into people's work. Such insights are essential for improving digital products in ways grounded in real-world user interactions. Prior research has applied deep learning models to cluster user actions into high-level activities, but these approaches are highly sensitive to noise and struggle to generalize across applications. To address this limitation, we introduce WorkflowView, a framework that uses large language models (LLMs) to abstract low-level action sequences into high-level activities. We establish the effectiveness and generality of our approach across three distinct, challenging sequential tasks and diverse domains: (a) zero-shot task description reconstruction from browser logs (achieving high semantic similarity, $\mu_{sim} = 0.91$), (b) few-shot student dropout prediction using MOOC interaction logs (reaching weighted $F_1 = 0.90$ with only five few-shot examples), and (c) anonymized, privacy-preserving analysis of AI tool integration within document workflows in Microsoft Word. Our work demonstrates that LLM-based abstraction is a robust and efficient path forward for transforming low-level behavioral data into high-level, interpretable, and actionable insights. We also discuss practical considerations for deploying LLM-based inferences within logging infrastructures, including computational efficiency and user privacy.

17.
Nature (Science) 2026-06-18

Daily briefing: The proteins that protect us from deadly mutations

Authors:

Proteins that ‘buffer’ the effects of mutations could help to treat diseases such as cancers. Plus, goats can follow human voices and the battle over a key ocean observatory project in the United States. Proteins that ‘buffer’ the effects of mutations could help to treat diseases such as cancers. Plus, goats can follow human voices and the battle over a key ocean observatory project in the United States.

18.
arXiv (CS.CL) 2026-06-15

Did You Forget What I Asked? Prospective Memory Failures in Large Language Models

Authors:

Large language models often fail to satisfy formatting instructions when they must simultaneously perform demanding tasks. We study this behaviour through a prospective memory inspired lens from cognitive psychology, using a controlled paradigm that combines verifiable formatting constraints with benchmark tasks of increasing complexity. Across three model families and over 8,000 prompts, compliance drops by 2-21% under concurrent task load. Vulnerability is highly type-dependent: terminal constraints (requiring action at the response boundary) degrade most, with drops up to 50%, while avoidance constraints remain comparatively robust. A salience-enhanced format (explicit instruction framing plus a trailing reminder) recovers much of the lost compliance, restoring performance to 90-100% in many settings. Interference is bidirectional: formatting constraints can also reduce task accuracy, with one model's GSM8K accuracy dropping from 93% to 27%. In additional stacking experiments, joint compliance declines sharply as constraints accumulate. All results use deterministic programmatic checkers without an LLM-as-judge component on publicly available datasets.

19.
arXiv (CS.LG) 2026-06-17

Exposing the Illusion of Fairness: Auditing Vulnerabilities to Distributional Manipulation Attacks

arXiv:2507.20708v3 Announce Type: replace Abstract: The rapid deployment of AI systems in high-stakes domains, including those classified as high-risk under the The EU AI Act (Regulation (EU) 2024/1689), has intensified the need for reliable compliance auditing. For binary classifiers, regulatory risk assessment often relies on global fairness metrics such as the Disparate Impact ratio, widely used to evaluate potential discrimination. In typical auditing settings, the auditee provides a subset of its dataset to an auditor, while a supervisory authority may verify whether this subset is representative of the full underlying distribution. In this work, we investigate to what extent a malicious auditee can construct a fairness-compliant yet representative-looking sample from a non-compliant original distribution, thereby creating an illusion of fairness. We formalize this problem as a constrained distributional projection task and introduce mathematically grounded manipulation strategies based on entropic and optimal transport projections. These constructions characterize the minimal distributional shift required to satisfy fairness constraints. To counter such attacks, we formalize representativeness through distributional distance based statistical tests and systematically evaluate their ability to detect manipulated samples. Our analysis highlights the conditions under which fairness manipulation can remain statistically undetected and provides practical guidelines for strengthening supervisory verification. We validate our theoretical findings through experiments on standard tabular datasets for bias detection. Code is publicly available at https://github.com/ValentinLafargue/Inspection.

20.
arXiv (math.PR) 2026-06-16

Free energy of non-convex multi-species spin glasses with centered Ising spins

arXiv:2606.16636v1 Announce Type: new Abstract: We identify the limit free energy of all multi-species spin glasses with centered $\pm 1$ spins. The result was previously known only under a convexity assumption on the covariance function of the Hamiltonian. We also obtain a one-species reduction of the formula for balanced multi-species models.

21.
arXiv (CS.AI) 2026-06-16

CAP: Towards PPG Universal Representation Learning with Patient-level Supervision

arXiv:2606.15284v1 Announce Type: cross Abstract: Photoplethysmography (PPG) plays a central role in wearable health monitoring and clinical decision support. Yet existing approaches to universal PPG representation learning largely focus on signal-level objectives and often overlook patient-level health context, which limits generalization to complex clinical tasks and heterogeneous cohorts. To address this gap, we construct a large-scale paired PPG-EHR multimodal dataset by distilling fragmented medical histories and clinical records into cohesive, patient-level electronic health records (EHR). Building on this resource, we propose Clinical Anchored Pretraining for PPG (CAP). During pretraining, CAP performs cross-modal contrastive alignment that anchors PPG representations to patient-level clinical semantics, guiding the encoder beyond waveform fitting toward modeling consistency in a patient's overall physiological state. During downstream adaptation, the pretrained PPG encoder provides clinically grounded representations that strengthen inductive bias and improve robustness and transferability. Experiments demonstrate that CAP consistently outperforms strong baselines on four diverse downstream tasks. CAP achieves a particularly large gain on respiratory rate prediction (up to +87.6% relative improvement over the state-of-the-art baseline) and delivers an average relative +26.7% across all tasks. We further enhance the interpretability of our approach through comprehensive analyses, including ablations and multiple complementary visualizations of the learned representations. The code for our experiments is available at: https://github.com/gody123gody/CAP .

22.
PLOS Computational Biology 2026-06-02

Data-driven model reveals increased stability of CAG-expanded <i>huntingtin</i> RNA due to MID1 binding

Authors:

by Yuhong Liu, Annika Reisbitzer, Domagoj Dorešić, Jan Hasenauer, Sybille Krauß, Tatjana Tchumatchenko RNA-binding proteins (RBP) are important regulators of RNA metabolism. In neurodegenerative disorders such as Huntington’s Disease (HD), disrupted RBP-RNA interactions contribute to neuronal dysfunction. One such RBP, Midline 1 (MID1), has been shown to aberrantly associate with mutant huntingtin (Htt) RNA, enhancing its translation, yet the mechanism driving this effect remains unknown. Here, we develop a computational model to understand the role of MID1. Based on previously published data, our model predicts that MID1 increases the stability of the Htt RNA. We experimentally validate this prediction, showing that overexpression of MID1 significantly prolongs the half-life of mutant Htt RNA. Furthermore, we evaluate model refinements, including clustering of MID1-bound RNA, which allow capturing all key observations in the data. Together, we provide a data-driven framework that underlines the importance of RBP-RNA interaction in post-transcriptional regulation. This framework also shows how individual molecular reactions jointly determine RNA stability and protein levels in HD.

23.
arXiv (CS.LG) 2026-06-15

Neural Variability Enhances Artificial Network Robustness

arXiv:2606.13801v1 Announce Type: new Abstract: Neural responses in cortex exhibit substantial trial-to-trial variability in response to repeated stimuli, while peripheral sensory neurons respond far more consistently, leading many to wonder whether stochasticity may carry meaning. Existing work has argued that noise and signal correlations may be optimized for discrimination in animals, whereas artificial neural network (ANN) studies have shown similar benefits of noise in machine learning tasks, although most ANN work has neglected the effects of correlations. Here we investigate whether correlated noise improves the robustness of artificial neural networks to adversarial attacks and naturalistic image modifications. Using the covariance of activations under modified versus clean inputs, we find that structured noise may significantly improve network robustness. Robustness to naturalistic image modifications benefits most from structure, but this structure transfers poorly across modification types. In contrast, noise structure from adversarial attacks can generalize to other kinds of attacks. These results suggest that structured noise in ANN activations generally improves robustness, establishing a biologically plausible strategy for creating robust artificial neural networks that only relies on local information.

24.
Nature (Science) 2026-06-10

Whole-genome duplication shaped cell-type evolution in the vertebrate brain

Authors:

The complex brains of vertebrates have more cell types than those of their closest relatives. Whole-genome duplications (WGDs) occurred during early vertebrate evolution1, but it is unclear whether the duplicated genes (ohnologues) facilitated cell-type evolution. Here using brain single-cell transcriptomes from five chordates—human2, mouse3, lizard4, lamprey5 and amphioxus—we report that many cell-type families with conserved core transcription factors in vertebrates do not show one-to-one homology with amphioxus. Moreover, ohnologues, particularly those from the first WGD, were more important than small-scale duplication paralogues for vertebrate cell-type evolution. To explore whether ohnologues are mechanistically important for this process, we predicted ancestral cell-type states and compared them to amphioxus and experimentally investigated macroglia. The findings indicate that ohnologues had a role in early vertebrate cell-type diversification. Moreover, by examining paralogue expression across cell types and species, we show that expression changes were mainly driven by dosage selection and subfunctionalization. We also link ohnologues to cellular diversity at different anatomical and cell-type scales. Our findings demonstrate the importance of WGDs for the evolution of early vertebrate brain complexity and highlight that the resultant ohnologues continued to capacitate cell-type evolution long after they were formed. Analyses of brain single-cell transcriptomes from human, mouse, lizard, lamprey and amphioxus reveal that duplicated genes (ohnologues) played a pivotal part in early vertebrate cell-type diversification.

25.
bioRxiv (Bioinfo) 2026-06-18

fuzzyfold: a high-performance framework for stochastic RNA folding kinetics

Authors:

The analysis of nucleic acid secondary structures is overwhelmingly dominated by methods that analyze the thermodynamic equilibrium distribution and which ignore all dynamic aspects of nucleic acid folding. Yet, there are numerous popular examples of nucleic acid folding that rely on kinetic models, such as RNA riboswitches or DNA strand displacement systems. Here, I am presenting fuzzyfold, a Rust-based software package for nucleic acid secondary structure analysis with an explicit focus on stochastic modeling. The framework introduces three-way and four-way shift moves with a biophysically motivated rate-model parameterization, and it is developed with an emphasis on both model flexibility and performance, e.g. allowing for the generation of single co-transcriptional trajectories for thousand-nucleotide long RNA molecules in just a few minutes. The main strength of the fuzzyfold package, however, is its focus on user and developer interfaces for long-term development. It provides easily installable command-line interfaces, e.g. for aggregating data from multiple parallel trajectories efficiently into an ensemble-level dynamic analysis. For developers, the code-base supports straight-forward substitution of thermodynamic and kinetic free-energy models, and a flexible library interface with Python bindings, enabling integration of individual components into custom computational workflows.