ArXiv最新文献

{"title":"RNA-FrameFlow: Flow Matching for de novo 3D RNA Backbone Design.","authors":"Rishabh Anand, Chaitanya K Joshi, Alex Morehead, Arian R Jamasb, Charles Harris, Simon V Mathis, Kieran Didi, Rex Ying, Bryan Hooi, Pietro Liò","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>We introduce RNA-FrameFlow, the first generative model for 3D RNA backbone design. We build upon <math><mi>S</mi> <mi>E</mi> <mo>(</mo> <mn>3</mn> <mo>)</mo></math> flow matching for protein backbone generation and establish protocols for data preparation and evaluation to address unique challenges posed by RNA modeling. We formulate RNA structures as a set of rigid-body frames and associated loss functions which account for larger, more conformationally flexible RNA backbones (13 atoms per nucleotide) vs. proteins (4 atoms per residue). Toward tackling the lack of diversity in 3D RNA datasets, we explore training with structural clustering and cropping augmentations. Additionally, we define a suite of evaluation metrics to measure whether the generated RNA structures are globally self-consistent (via inverse folding followed by forward folding) and locally recover RNA-specific structural descriptors. The most performant version of RNA-FrameFlow generates locally realistic RNA backbones of 40-150 nucleotides, over 40% of which pass our validity criteria as measured by a self-consistency TM-score ≥ 0.45, at which two RNAs have the same global fold. Open-source code: github.com/rish-16/rna-backbone-design.</p>","PeriodicalId":93888,"journal":{"name":"ArXiv","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11213149/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141473428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From Density to Void: Why Brain Networks Fail to Reveal Complex Higher-Order Structures.","authors":"Moo K Chung, Anass B El-Yaagoubi, Anqi Qiu, Hernando Ombao","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>In brain network analysis using resting-state fMRI, there is growing interest in modeling higher-order interactions beyond simple pairwise connectivity via persistent homology. Despite the promise of these advanced topological tools, robust and consistently observed higher-order interactions over time remain elusive. In this study, we investigate why conventional analyses often fail to reveal complex higher-order structures - such as interactions involving four or more nodes - and explore whether such interactions truly exist in functional brain networks. We utilize a simplicial complex framework often used in persistent homology to address this question.</p>","PeriodicalId":93888,"journal":{"name":"ArXiv","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11957234/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143756457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Costs and benefits of phytoplankton motility.","authors":"Peyman Fahimi, Andrew J Irwin, Michael Lynch","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The motility skills of phytoplankton have evolved and persisted over millions of years, primarily in response to factors such as nutrient and light availability, temperature and viscosity gradients, turbulence, and predation pressure. Phytoplankton motility is broadly categorized into swimming and buoyancy regulation. Despite studies in the literature exploring the motility costs and benefits of phytoplankton, there remains a gap in our integrative understanding of direct and indirect energy expenditures, starting from when an organism initiates movement due to any biophysical motive, to when the organism encounters intracellular and environmental challenges. Here we gather all available pieces of this puzzle from literature in biology, physics, and oceanography to paint an overarching picture of our current knowledge. The characterization of sinking and rising behavior as passive motility has resulted in the concept of sinking and rising internal efficiency being overlooked. We define this efficiency based on any energy dissipation associated with processes of mass density adjustment, as exemplified in structures like frustules and vacuoles. We propose that sinking and rising are active motility processes involving non-visible mechanisms, as species demonstrate active and rapid strategies in response to turbulence, predation risk, and gradients of nutrients, light, temperature, and viscosity. Identifying intracellular buoyancy-regulating dissipative processes offers deeper insight into the motility costs relative to the organism's total metabolic rate.</p>","PeriodicalId":93888,"journal":{"name":"ArXiv","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11957218/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143756424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Approximate Hamilton-Jacobi Reachability Analysis for a Class of Two-Timescale Systems, with Application to Biological Models.","authors":"Dylan Hirsch, Sylvia Herbert","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Hamilton-Jacobi reachability (HJR) is an exciting framework used for control of safety-critical systems with nonlinear and possibly uncertain dynamics. However, HJR suffers from the curse of dimensionality, with computation times growing exponentially in the dimension of the system state. Many autonomous and controlled systems involve dynamics that evolve on multiple timescales, and for these systems, singular perturbation methods can be used for model reduction. However, such methods are more challenging to apply in HJR due to the presence of an underlying differential game. In this work, we leverage prior work on singularly perturbed differential games to identify a class of systems which can be readily reduced, and we relate these results to the quantities of interest in HJR. We demonstrate the utility of our results on two examples involving biological systems, where dynamics fitting the identified class are frequently encountered.</p>","PeriodicalId":93888,"journal":{"name":"ArXiv","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11952577/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143756342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Subthreshold moment analysis of neuronal populations driven by synchronous synaptic inputs.","authors":"Logan A Becker, Francois Baccelli, Thibaud Taillefumier","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Even when driven by the same stimulus, neuronal responses are well-known to exhibit a striking level of spiking variability. In-vivo electrophysiological recordings also reveal a surprisingly large degree of variability at the subthreshold level. In prior work, we considered biophysically relevant neuronal models to account for the observed magnitude of membrane voltage fluctuations. We found that accounting for these fluctuations requires weak but nonzero synchrony in the spiking activity, in amount that are consistent with experimentally measured spiking correlations. Here we investigate whether such synchrony can explain additional statistical features of the measured neural activity, including neuronal voltage covariability and voltage skewness. Addressing this question involves conducting a generalized moment analysis of conductance-based neurons in response to input drives modeled as correlated jump processes. Technically, we perform such an analysis using fixed-point techniques from queuing theory that are applicable in the stationary regime of activity. We found that weak but nonzero synchrony can consistently explain the experimentally reported voltage covariance and skewness. This confirms the role of synchrony as a primary driver of cortical variability and supports that physiological neural activity emerges as a population-level phenomenon, especially in the spontaneous regime.</p>","PeriodicalId":93888,"journal":{"name":"ArXiv","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11957229/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143756440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MicroVQA: A Multimodal Reasoning Benchmark for Microscopy-Based Scientific Research.","authors":"James Burgess, Jeffrey J Nirschl, Laura Bravo-Sánchez, Alejandro Lozano, Sanket Rajan Gupte, Jesus G Galaz-Montoya, Yuhui Zhang, Yuchang Su, Disha Bhowmik, Zachary Coman, Sarina M Hasan, Alexandra Johannesson, William D Leineweber, Malvika G Nair, Ridhi Yarlagadda, Connor Zuraski, Wah Chiu, Sarah Cohen, Jan N Hansen, Manuel D Leonetti, Chad Liu, Emma Lundberg, Serena Yeung-Levy","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Scientific research demands sophisticated reasoning over multimodal data, a challenge especially prevalent in biology. Despite recent advances in multimodal large language models (MLLMs) for AI-assisted research, existing multimodal reasoning benchmarks only target up to college-level difficulty, while research-level benchmarks emphasize lower-level perception, falling short of the complex multimodal reasoning needed for scientific discovery. To bridge this gap, we introduce MicroVQA, a visual-question answering (VQA) benchmark designed to assess three reasoning capabilities vital in research workflows: expert image understanding, hypothesis generation, and experiment proposal. MicroVQA consists of 1,042 multiple-choice questions (MCQs) curated by biology experts across diverse microscopy modalities, ensuring VQA samples represent real scientific practice. In constructing the benchmark, we find that standard MCQ generation methods induce language shortcuts, motivating a new two-stage pipeline: an optimized LLM prompt structures question-answer pairs into MCQs; then, an agent-based `RefineBot' updates them to remove shortcuts. Benchmarking on state-of-the-art MLLMs reveal a peak performance of 53%; models with smaller LLMs only slightly underperform top models, suggesting that language-based reasoning is less challenging than multimodal reasoning; and tuning with scientific articles enhances performance. Expert analysis of chain-of-thought responses shows that perception errors are the most frequent, followed by knowledge errors and then overgeneralization errors. These insights highlight the challenges in multimodal scientific reasoning, showing MicroVQA is a valuable resource advancing AI-driven biomedical research. MicroVQA is available at https://huggingface.co/datasets/jmhb/microvqa, and project page at https://jmhb0.github.io/microvqa.</p>","PeriodicalId":93888,"journal":{"name":"ArXiv","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11957224/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143756493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Joint estimation of activity, attenuation and motion in respiratory-self-gated time-of-flight PET.","authors":"Masoud Elhamiasl, Frederic Jolivet, Ahmadreza Rezaei, Michael Fieseler, Klaus Schäfers, Johan Nuyts, Georg Schramm, Fernando Boada","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Whole-body PET imaging is often hindered by respiratory motion during acquisition, causing significant degradation in the quality of reconstructed activity images. An additional challenge in PET/CT imaging arises from the respiratory phase mismatch between CT-based attenuation correction and PET acquisition, leading to attenuation artifacts. To address these issues, we propose two new, purely data-driven methods for the joint estimation of activity, attenuation, and motion in respiratory self-gated TOF PET. These methods enable the reconstruction of a single activity image free from motion and attenuation artifacts. The proposed methods were evaluated using data from the anthropomorphic Wilhelm phantom acquired on a Siemens mCT PET/CT system, as well as 3 clinical FDG PET/CT datasets acquired on a GE DMI PET/CT system. Image quality was assessed visually to identify motion and attenuation artifacts. Lesion uptake values were quantitatively compared across reconstructions without motion modeling, with motion modeling but static attenuation correction, and with our proposed methods. For the Wilhelm phantom, the proposed methods delivered image quality closely matching the reference reconstruction from a static acquisition. The lesion-to-background contrast for a liver dome lesion improved from 2.0 (no motion correction) to 5.2 (proposed methods), matching the contrast from the static acquisition (5.2). In contrast, motion modeling with static attenuation correction yielded a lower contrast of 3.5. In patient datasets, the proposed methods successfully reduced motion artifacts in lung and liver lesions and mitigated attenuation artifacts, demonstrating superior lesion to background separation. Our proposed methods enable the reconstruction of a single, high-quality activity image that is motion-corrected and free from attenuation artifacts, without the need for external hardware.</p>","PeriodicalId":93888,"journal":{"name":"ArXiv","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11702814/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143018059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Causes of evolutionary divergence in prostate cancer.","authors":"Emre Esenturk, Atef Sahli, Valeriia Haberland, Aleksandra Ziuboniewicz, Christopher Wirth, G Steven Bova, Robert G Bristow, Mark N Brook, Benedikt Brors, Adam Butler, Géraldine Cancel-Tassin, Kevin Cl Cheng, Colin S Cooper, Niall M Corcoran, Olivier Cussenot, Ros A Eeles, Francesco Favero, Clarissa Gerhauser, Abraham Gihawi, Etsehiwot G Girma, Vincent J Gnanapragasam, Andreas J Gruber, Anis Hamid, Vanessa M Hayes, Housheng Hansen He, Christopher M Hovens, Eddie Luidy Imada, G Maria Jakobsdottir, Chol-Hee Jung, Francesca Khani, Zsofia Kote-Jarai, Philippe Lamy, Gregory Leeman, Massimo Loda, Pavlo Lutsik, Luigi Marchionni, Ramyar Molania, Anthony T Papenfuss, Diogo Pellegrina, Bernard Pope, Lucio R Queiroz, Tobias Rausch, Jüri Reimand, Brian Robinson, Thorsten Schlomm, Karina D Sørensen, Sebastian Uhrig, Joachim Weischenfeldt, Yaobo Xu, Takafumi N Yamaguchi, Claudio Zanettini, Andy G Lynch, David C Wedge, Daniel S Brewer, Dan J Woodcock","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Cancer progression involves the sequential accumulation of genetic alterations that cumulatively shape the tumour phenotype. In prostate cancer, tumours can follow divergent evolutionary trajectories that lead to distinct subtypes, but the causes of this divergence remain unclear. While causal inference could elucidate the factors involved, conventional methods are unsuitable due to the possibility of unobserved confounders and ambiguity in the direction of causality. Here, we propose a method that circumvents these issues and apply it to genomic data from 829 prostate cancer patients. We identify several genetic alterations that drive divergence as well as others that prevent this transition, locking tumours into one trajectory. Further analysis reveals that these genetic alterations may cause each other, implying a positive-feedback loop that accelerates divergence. Our findings provide insights into how cancer subtypes emerge and offer a foundation for genomic surveillance strategies aimed at monitoring the progression of prostate cancer.</p>","PeriodicalId":93888,"journal":{"name":"ArXiv","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11957227/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143756420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Self-Supervised Z-Slice Augmentation for 3D Bio-Imaging via Knowledge Distillation.","authors":"Alessandro Pasqui, Sajjad Mahdavi, Benoit Vianay, Alexandra Colin, Rémi Dumollard, Alex McDougall, Yekaterina A Miroshnikova, Elsa Labrune, Hervé Turlier","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Three-dimensional biological microscopy has significantly advanced our understanding of complex biological structures. However, limitations due to microscopy techniques, sample properties or phototoxicity often result in poor z-resolution, hindering accurate cellular measurements. Here, we introduce ZAugNet, a fast, accurate, and self-supervised deep learning method for enhancing z-resolution in biological images. By performing nonlinear interpolation between consecutive slices, ZAugNet effectively doubles resolution with each iteration. Compared on several microscopy modalities and biological objects, it outperforms competing methods on most metrics. Our method leverages a generative adversarial network (GAN) architecture combined with knowledge distillation to maximize prediction speed without compromising accuracy. We also developed ZAugNet+, an extended version enabling continuous interpolation at arbitrary distances, making it particularly useful for datasets with nonuniform slice spacing. Both ZAugNet and ZAugNet+ provide high-performance, scalable z-slice augmentation solutions for large-scale 3D imaging. They are available as open-source frameworks in PyTorch, with an intuitive Colab notebook interface for easy access by the scientific community.</p>","PeriodicalId":93888,"journal":{"name":"ArXiv","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11908362/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143652600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Causal Representation Learning from Multimodal Biomedical Observations.","authors":"Yuewen Sun, Lingjing Kong, Guangyi Chen, Loka Li, Gongxu Luo, Zijian Li, Yixuan Zhang, Yujia Zheng, Mengyue Yang, Petar Stojanov, Eran Segal, Eric P Xing, Kun Zhang","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Prevalent in biomedical applications (e.g., human phenotype research), multimodal datasets can provide valuable insights into the underlying physiological mechanisms. However, current machine learning (ML) models designed to analyze these datasets often lack interpretability and identifiability guarantees, which are essential for biomedical research. Recent advances in causal representation learning have shown promise in identifying interpretable latent causal variables with formal theoretical guarantees. Unfortunately, most current work on multimodal distributions either relies on restrictive parametric assumptions or yields only coarse identification results, limiting their applicability to biomedical research that favors a detailed understanding of the mechanisms. In this work, we aim to develop flexible identification conditions for multimodal data and principled methods to facilitate the understanding of biomedical datasets. Theoretically, we consider a nonparametric latent distribution (c.f., parametric assumptions in previous work) that allows for causal relationships across potentially different modalities. We establish identifiability guarantees for each latent component, extending the subspace identification results from previous work. Our key theoretical contribution is the structural sparsity of causal connections between modalities, which, as we will discuss, is natural for a large collection of biomedical systems. Empirically, we present a practical framework to instantiate our theoretical insights. We demonstrate the effectiveness of our approach through extensive experiments on both numerical and synthetic datasets. Results on a real-world human phenotype dataset are consistent with established biomedical research, validating our theoretical and methodological framework.</p>","PeriodicalId":93888,"journal":{"name":"ArXiv","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11952583/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143756344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}