Aperiodic neural activity has been the subject of intense research interest lately as it could reflect on the cortical excitation/inhibition ratio, which is suspected to be affected in numerous clinical conditions. This phenomenon is characterized via the aperiodic scaling exponent $\beta$, equal to the spectral slope following log-log transformation of power spectra. Despite recent progress, however, most current methods do not take into consideration the plausible multimodal nature in the power spectra of neurophysiological recordings - i.e., $\beta$ might be different in low- ($\beta_{lo}$) and high-frequency ($\beta_{hi}$) regimes -, especially in case of $|\beta_{lo}|>|\beta_{hi}|$. Here we propose an algorithm, the multi-modal spectral parametrization method (MMSPM) that aims to account for this issue. MMSPM estimates $\beta_{lo}$ and $\beta_{hi}$ separately using a constrained, piece-wise regression technique, and also assesses if they are significantly different or instead the spectrum is indeed unimodal and can be characterized simply with broadband $\beta$. Here we present the MMSPM algorithm and evaluate its performance in silico on simulated power spectra. Then, we use MMSPM on resting-state electroencephalography (EEG) data collected from 19 young, healthy volunteers, as well as on a separate dataset of EEG recordings from 30 schizophrenia patients and 31 healthy controls, and demonstrate that broadband (0.1-100 Hz and 0.5-45 Hz) EEG spectra can indeed present a bimodality pattern with significantly steeper low-range ($<\sim2$ Hz) and flatter high-range scaling regimes (i.e., $|\beta_{lo}|>|\beta_{hi}|$). Clinical relevance: The MMSPM method characterizes aperiodic neural activity in distinct scaling regimes, which can be relevant in numerous pathological conditions such as dementia or schizophrenia.
Background In proteomics, the most probable localizations of post-translational modifications are assessed by localization scores evaluating the likelihood of a given modification to occupy a site on a peptide sequence. When identifying highly modified peptides, localization scores for different modifications can return conflicting results, stacking modifications on the same amino acid. Here, we propose a graph-based approach that assigns modifications to sites in a way that maximizes localization scores while avoiding conflicting assignments. Results The algorithm is implemented as both a standalone Python program and in the compomics-utilities Java library. Our graph-based approach showed the ability to match complex combinations of modifications and acceptor sites, allowing the processing of thousands of peptides in a few seconds. Conclusions Our graph-based approach to modification site assignment allows distributing multiple modifications in a way that maximizes individual localization scores. Having an optimal modification site assignment is important for spectrum annotation and biological interpretation.
A major goal of neuroscience is to understand brain computations during visual processing in naturalistic settings. A dominant approach is to use image-computable deep neural networks trained with different task objectives as a basis for linear encoding models. However, in addition to requiring tuning a large number of parameters, the linear encoding approach ignores the structure of the feature maps both in the brain and the models. Recently proposed alternatives have focused on decomposing the linear mapping to spatial and feature components but focus on finding static receptive fields for units that are applicable only in early visual areas. In this work, we employ the attention mechanism used in the transformer architecture to study how retinotopic visual features can be dynamically routed to category-selective areas in high-level visual processing. We show that this computational motif is significantly more powerful than alternative methods in predicting brain activity during natural scene viewing, across different feature basis models and modalities. We also show that this approach is inherently more interpretable, without the need to create importance maps, by interpreting the attention routing signal for different high-level categorical areas. Our approach proposes a mechanistic model of how visual information from retinotopic maps can be routed based on the relevance of the input content to different category-selective regions.
Large language models (LLMs) have revolutionized natural language processing and are increasingly applied to other sequential data types, including genetic sequences. However, adapting LLMs to genomics presents significant challenges. Capturing complex genomic interactions requires modeling long-range dependencies within DNA sequences, where interactions often span over 10,000 base pairs, even within a single gene, posing substantial computational burdens under conventional model architectures and training paradigms. Moreover, standard LLM training approaches are suboptimal for DNA: autoregressive training, while efficient, supports only unidirectional understanding. However, DNA is inherently bidirectional, e.g., bidirectional promoters regulate transcription in both directions and account for nearly 11% of human gene expression. Masked language models (MLMs) allow bidirectional understanding but are inefficient, as only masked tokens contribute to the loss per step. To address these limitations, we introduce JanusDNA, the first bidirectional DNA foundation model built upon a novel pretraining paradigm that combines the optimization efficiency of autoregressive modeling with the bidirectional comprehension of masked modeling. JanusDNA adopts a hybrid Mamba, Attention and Mixture of Experts (MoE) architecture, combining long-range modeling of Attention with efficient sequential learning of Mamba. MoE layers further scale model capacity via sparse activation while keeping computational cost low. Notably, JanusDNA processes up to 1 million base pairs at single nucleotide resolution on a single 80GB GPU. Extensive experiments and ablations show JanusDNA achieves new SOTA results on three genomic representation benchmarks, outperforming models with 250x more activated parameters. Code: https://github.com/Qihao-Duan/JanusDNA
To be fully useful for public health practice, models for epidemic response must be able to do more than predict -- it is also important to incorporate the mechanisms underlying transmission dynamics to enable policymakers and practitioners to be able to evaluate what-if scenarios and intervention options. However, most mechanistic models suffer from uncertainty in both the parameters (e.g., parameter unidentifiability) and the model structure itself, which can hinder both successful parameter estimation and model interpretation. To enable rapid development of interpretable and parsimonious mechanistic models, we use penalized regression and covariate selection methods to integrate parameter identifiability and model selection directly into the parameter estimation procedure for (in this case) traditional ordinary differential equation (ODE) models. For both simulated and real-world epidemiological data, we demonstrate that the LASSO-ODE framework is highly effective in selecting a parsimonious, identifiable model from larger, more realistic but potentially unidentifiable models, from realistically sparse data with only a single measured compartment and multiple latent (unobserved) variables. While we focus on epidemic models in this paper as a case study, these same approaches are applicable to a wide range of application areas that are faced with relatively sparse data but a need for realistic mechanistic models (e.g. mathematical oncology and mathematical biology more broadly). Additionally, the cross-validation techniques designed for time series data introduced in our study can be used across a range of time series analysis and modeling approaches.
Time-series single-cell RNA-sequencing (scRNA-seq) datasets offer unprecedented insights into the dynamics and heterogeneity of cellular systems. These systems exhibit multiscale collective behaviors driven by intricate intracellular gene regulatory networks and intercellular interactions of molecules. However, inferring interacting cell population dynamics from time-series scRNA-seq data remains a significant challenge, as cells are isolated and destroyed during sequencing. To address this, we introduce scIMF, a single-cell deep generative Interacting Mean Field model, designed to learn collective multi-cellular dynamics. Our approach leverages a transformer-enhanced stochastic differential equation network to simultaneously capture cell-intrinsic dynamics and intercellular interactions. Through extensive benchmarking on multiple scRNA-seq datasets, scIMF outperforms existing methods in reconstructing gene expression at held-out time points, demonstrating that modeling cell-cell communication enhances the accuracy of multicellular dynamics characterization.Additionally, our model provides biologically interpretable insights into cell-cell interactions during dynamic processes, offering a powerful tool for understanding complex cellular systems.
Plasmodium falciparum is responsible for the majority of malaria morbidity and mortality each year. Malaria transmission rates vary by location and time of year due to climate and environmental conditions. We show the impact of these factors by developing a stochastic spatiotemporal agent-based malaria model that captures the impact of spatially distributed interventions on malaria transmission. Our model uses spatiotemporal estimates of mosquito climatic suitability and household location data to model the interaction between human and mosquito agents. We apply our model to investigate how strategies for distributing interventions to households in Vietnam impact the disease burden. Our study shows that providing some level of protection to a wide range of households reduces malaria prevalence more compared to providing a strong level of protection to a limited number of households.
The identification of bitter peptides is crucial in various domains, including food science, drug discovery, and biochemical research. These peptides not only contribute to the undesirable taste of hydrolyzed proteins but also play key roles in physiological and pharmacological processes. However, experimental methods for identifying bitter peptides are time-consuming and expensive. With the rapid expansion of peptide sequence databases in the post-genomic era, the demand for efficient computational approaches to distinguish bitter from non-bitter peptides has become increasingly significant. In this study, we propose a novel stacking-based ensemble learning framework aimed at enhancing the accuracy and reliability of bitter peptide classification. Our method integrates diverse sequence-based feature representations and leverages a broad set of machine learning classifiers. The first stacking layer comprises multiple base classifiers, each trained on distinct feature encoding schemes, while the second layer employs logistic regression to refine predictions using an eight-dimensional probability vector. Extensive evaluations on a carefully curated dataset demonstrate that our model significantly outperforms existing predictive methods, providing a robust and reliable computational tool for bitter peptide identification. Our approach achieves an accuracy of 96.09\% and a Matthews Correlation Coefficient (MCC) of 0.9220 on the independent test set, underscoring its effectiveness and generalizability. To facilitate real-time usage and broader accessibility, we have also developed a user-friendly web server based on the proposed method, which is freely accessible at https://ibitter-stack-webserver.streamlit.app/. This tool enables researchers and practitioners to conveniently screen peptide sequences for bitterness in real-time applications.
Developing high-performance software is a complex task that requires specialized expertise. We introduce GSO, a benchmark for evaluating language models' capabilities in developing high-performance software. We develop an automated pipeline that generates and executes performance tests to analyze repository commit histories to identify 102 challenging optimization tasks across 10 codebases, spanning diverse domains and programming languages. An agent is provided with a codebase and performance test as a precise specification, and tasked to improve the runtime efficiency, which is measured against the expert developer optimization. Our quantitative evaluation reveals that leading SWE-Agents struggle significantly, achieving less than 5% success rate, with limited improvements even with inference-time scaling. Our qualitative analysis identifies key failure modes, including difficulties with low-level languages, practicing lazy optimization strategies, and challenges in accurately localizing bottlenecks. We release the code and artifacts of our benchmark along with agent trajectories to enable future research.
Language models (LMs) perform well on standardized coding benchmarks but struggle with real-world software engineering tasks such as resolving GitHub issues in SWE-Bench, especially when model parameters are less than 100B. While smaller models are preferable in practice due to their lower computational cost, improving their performance remains challenging. Existing approaches primarily rely on supervised fine-tuning (SFT) with high-quality data, which is expensive to curate at scale. An alternative is test-time scaling: generating multiple outputs, scoring them using a verifier, and selecting the best one. Although effective, this strategy often requires excessive sampling and costly scoring, limiting its practical application. We propose Evolutionary Test-Time Scaling (EvoScale), a sample-efficient method that treats generation as an evolutionary process. By iteratively refining outputs via selection and mutation, EvoScale shifts the output distribution toward higher-scoring regions, reducing the number of samples needed to find correct solutions. To reduce the overhead from repeatedly sampling and selection, we train the model to self-evolve using reinforcement learning (RL). Rather than relying on external verifiers at inference time, the model learns to self-improve the scores of its own generations across iterations. Evaluated on SWE-Bench-Verified, EvoScale enables our 32B model, Satori-SWE-32B, to match or exceed the performance of models with over 100B parameters while using a few samples. Code, data, and models will be fully open-sourced.
This paper investigates the ability of large language models (LLMs) to recognise and solve tasks which have been obfuscated beyond recognition. Focusing on competitive programming and benchmark tasks (LeetCode and MATH), we compare performance across multiple models and obfuscation methods, such as noise and redaction. We demonstrate that all evaluated LLMs can solve tasks obfuscated to a level where the text would be unintelligible to human readers, and does not contain key pieces of instruction or context. We introduce the concept of eager pattern matching to describe this behaviour, which is not observed in tasks published after the models' knowledge cutoff date, indicating strong memorisation or overfitting to training data, rather than legitimate reasoning about the presented problem. We report empirical evidence of distinct performance decay patterns between contaminated and unseen datasets. We discuss the implications for benchmarking and evaluations of model behaviour, arguing for caution when designing experiments using standard datasets. We also propose measuring the decay of performance under obfuscation as a possible strategy for detecting dataset contamination and highlighting potential safety risks and interpretability issues for automated software systems.
Multilook coherent imaging is a widely used technique in applications such as digital holography, ultrasound imaging, and synthetic aperture radar. A central challenge in these systems is the presence of multiplicative noise, commonly known as speckle, which degrades image quality. Despite the widespread use of coherent imaging systems, their theoretical foundations remain relatively underexplored. In this paper, we study both the theoretical and algorithmic aspects of likelihood-based approaches for multilook coherent imaging, providing a rigorous framework for analysis and method development. Our theoretical contributions include establishing the first theoretical upper bound on the Mean Squared Error (MSE) of the maximum likelihood estimator under the deep image prior hypothesis. Our results capture the dependence of MSE on the number of parameters in the deep image prior, the number of looks, the signal dimension, and the number of measurements per look. On the algorithmic side, we employ projected gradient descent (PGD) as an efficient method for computing the maximum likelihood solution. Furthermore, we introduce two key ideas to enhance the practical performance of PGD. First, we incorporate the Newton-Schulz algorithm to compute matrix inverses within the PGD iterations, significantly reducing computational complexity. Second, we develop a bagging strategy to mitigate projection errors introduced during PGD updates. We demonstrate that combining these techniques with PGD yields state-of-the-art performance. Our code is available at https://github.com/Computational-Imaging-RU/Bagged-DIP-Speckle.
Spoken language models (SLMs) operate on acoustic units obtained by discretizing self-supervised speech representations. Although the characteristics of these units directly affect performance, the interaction between codebook size and unit coarseness (i.e., duration) remains unexplored. We investigate SLM performance as we vary codebook size and unit coarseness using the simple duration-penalized dynamic programming (DPDP) method. New analyses are performed across different linguistic levels. At the phone and word levels, coarseness provides little benefit, as long as the codebook size is chosen appropriately. However, when producing whole sentences in a resynthesis task, SLMs perform better with coarser units. In lexical and syntactic language modeling tasks, coarser units also give higher accuracies at lower bitrates. We therefore show that coarser units aren't always better, but that DPDP is a simple and efficient way to obtain coarser units for the tasks where they are beneficial.
Opinion mining plays a vital role in analysing user feedback and extracting insights from textual data. While most research focuses on sentiment polarity (e.g., positive, negative, neutral), fine-grained emotion classification in app reviews remains underexplored. This paper addresses this gap by identifying and addressing the challenges and limitations in fine-grained emotion analysis in the context of app reviews. Our study adapts Plutchik's emotion taxonomy to app reviews by developing a structured annotation framework and dataset. Through an iterative human annotation process, we define clear annotation guidelines and document key challenges in emotion classification. Additionally, we evaluate the feasibility of automating emotion annotation using large language models, assessing their cost-effectiveness and agreement with human-labelled data. Our findings reveal that while large language models significantly reduce manual effort and maintain substantial agreement with human annotators, full automation remains challenging due to the complexity of emotional interpretation. This work contributes to opinion mining by providing structured guidelines, an annotated dataset, and insights for developing automated pipelines to capture the complexity of emotions in app reviews.
We introduce CTIM-Rover, an AI agent for Software Engineering (SE) built on top of AutoCodeRover (Zhang et al., 2024) that extends agentic reasoning frameworks with an episodic memory, more specifically, a general and repository-level Cross-Task-Instance Memory (CTIM). While existing open-source SE agents mostly rely on ReAct (Yao et al., 2023b), Reflexion (Shinn et al., 2023), or Code-Act (Wang et al., 2024), all of these reasoning and planning frameworks inefficiently discard their long-term memory after a single task instance. As repository-level understanding is pivotal for identifying all locations requiring a patch for fixing a bug, we hypothesize that SE is particularly well positioned to benefit from CTIM. For this, we build on the Experiential Learning (EL) approach ExpeL (Zhao et al., 2024), proposing a Mixture-Of-Experts (MoEs) inspired approach to create both a general-purpose and repository-level CTIM. We find that CTIM-Rover does not outperform AutoCodeRover in any configuration and thus conclude that neither ExpeL nor DoT-Bank (Lingam et al., 2024) scale to real-world SE problems. Our analysis indicates noise introduced by distracting CTIM items or exemplar trajectories as the likely source of the performance degradation.
The issue-resolving task, where a model generates patches to fix real-world bugs, has emerged as a critical benchmark for evaluating the capabilities of large language models (LLMs). While SWE-bench and its variants have become standard in this domain, they suffer from key limitations: they have not been updated since their initial releases, cover a narrow set of repositories, and depend heavily on manual effort for instance construction and environment setup. These factors hinder scalability and introduce risks of overfitting and data contamination. In this work, we present SWE-bench-Live, a live-updatable benchmark designed to overcome these challenges. Our initial release consists of 1,319 tasks derived from real GitHub issues created since 2024, spanning 93 repositories. Each task is accompanied by a dedicated Docker image to ensure reproducible execution. Central to our benchmark is \method, an automated curation pipeline that streamlines the entire process from instance creation to environment setup, removing manual bottlenecks and enabling scalability and continuous updates. We evaluate a range of state-of-the-art agent frameworks and LLMs on SWE-bench-Live, revealing a substantial performance gap compared to static benchmarks like SWE-bench, even under controlled evaluation conditions. To better understand this discrepancy, we perform detailed analyses across repository origin, issue recency, and task difficulty. By providing a fresh, diverse, and executable benchmark grounded in live repository activity, SWE-bench-Live facilitates rigorous, contamination-resistant evaluation of LLMs and agents in dynamic, real-world software development settings.
We propose a self-supervised feature learning assisted reconstruction (SSFL-Recon) framework for MRI reconstruction to address the limitation of existing supervised learning methods. Although recent deep learning-based methods have shown promising performance in MRI reconstruction, most require fully-sampled images for supervised learning, which is challenging in practice considering long acquisition times under respiratory or organ motion. Moreover, nearly all fully-sampled datasets are obtained from conventional reconstruction of mildly accelerated datasets, thus potentially biasing the achievable performance. The numerous undersampled datasets with different accelerations in clinical practice, hence, remain underutilized. To address these issues, we first train a self-supervised feature extractor on undersampled images to learn sampling-insensitive features. The pre-learned features are subsequently embedded in the self-supervised reconstruction network to assist in removing artifacts. Experiments were conducted retrospectively on an in-house 2D cardiac Cine dataset, including 91 cardiovascular patients and 38 healthy subjects. The results demonstrate that the proposed SSFL-Recon framework outperforms existing self-supervised MRI reconstruction methods and even exhibits comparable or better performance to supervised learning up to $16\times$ retrospective undersampling. The feature learning strategy can effectively extract global representations, which have proven beneficial in removing artifacts and increasing generalization ability during reconstruction.
Quantitative susceptibility maps from magnetic resonance images can provide both prognostic and diagnostic information in multiple sclerosis, a neurodegenerative disease characterized by the formation of lesions in white matter brain tissue. In particular, susceptibility maps provide adequate contrast to distinguish between "rim" lesions, surrounded by deposited paramagnetic iron, and "non-rim" lesion types. These paramagnetic rim lesions (PRLs) are an emerging biomarker in multiple sclerosis. Much effort has been devoted to both detection and segmentation of such lesions to monitor longitudinal change. As paramagnetic rim lesions are rare, addressing this problem requires confronting the class imbalance between rim and non-rim lesions. We produce synthetic quantitative susceptibility maps of paramagnetic rim lesions and show that inclusion of such synthetic data improves classifier performance and provide a multi-channel extension to generate accompanying contrasts and probabilistic segmentation maps. We exploit the projection capability of our trained generative network to demonstrate a novel denoising approach that allows us to train on ambiguous rim cases and substantially increase the minority class. We show that both synthetic lesion synthesis and our proposed rim lesion label denoising method best approximate the unseen rim lesion distribution and improve detection in a clinically interpretable manner. We release our code and generated data at https://github.com/agr78/PRLx-GAN upon publication.
Nonadiabatic couplings (NACs) play a crucial role in modeling photochemical and photophysical processes with methods such as the widely used fewest-switches surface hopping (FSSH). There is therefore a strong incentive to machine learn NACs for accelerating simulations. However, this is challenging due to NACs' vectorial, double-valued character and the singularity near a conical intersection seam. For the first time, we design NAC-specific descriptors based on our domain expertise and show that they allow learning NACs with never-before-reported accuracy of $R^2$ exceeding 0.99. The key to success is also our new ML phase-correction procedure. We demonstrate the efficiency and robustness of our approach on a prototypical example of fully ML-driven FSSH simulations of fulvene targeting the SA-2-CASSCF(6,6) electronic structure level. This ML-FSSH dynamics leads to an accurate description of $S_1$ decay while reducing error bars by allowing the execution of a large ensemble of trajectories. Our implementations are available in open-source MLatom.
Usability evaluation is critical to the impact and adoption of open source software (OSS), yet traditional methods relying on human evaluators suffer from high costs and limited scalability. To address these limitations, we introduce OSS-UAgent, an automated, configurable, and interactive agent-based usability evaluation framework specifically designed for open source software. Our framework employs intelligent agents powered by large language models (LLMs) to simulate developers performing programming tasks across various experience levels (from Junior to Expert). By dynamically constructing platform-specific knowledge bases, OSS-UAgent ensures accurate and context-aware code generation. The generated code is automatically evaluated across multiple dimensions, including compliance, correctness, and readability, providing a comprehensive measure of the software's usability. Additionally, our demonstration showcases OSS-UAgent's practical application in evaluating graph analytics platforms, highlighting its effectiveness in automating usability evaluation.