ArXiv最新文献

{"title":"Controlling tissue size by active fracture.","authors":"Wei Wang, Brian A Camley","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Groups of cells, including clusters of cancerous cells, multicellular organisms, and developing organs, may both grow and break apart. What physical factors control these fractures? In these processes, what sets the eventual size of clusters? We develop a framework for understanding cell clusters that can fragment due to cell motility using an active particle model. We compute analytically how the break rate of cell-cell junctions depends on cell speed, cell persistence, and cell-cell junction properties. Next, we find the cluster size distributions, which differ depending on whether all cells can divide or only the cells on the edge of the cluster divide. Cluster size distributions depend solely on the ratio of the break rate to the growth rate - allowing us to predict how cluster size and variability depend on cell motility and cell-cell mechanics. Our results suggest that organisms can achieve better size control when cell division is restricted to the cluster boundaries or when fracture can be localized to the cluster center. Our results link the general physics problem of a collective active escape over a barrier to size control, providing a quantitative measure of how motility can regulate organ or organism size.</p>","PeriodicalId":93888,"journal":{"name":"ArXiv","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11908369/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143652571","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":"Multimodal AI predicts clinical outcomes of drug combinations from preclinical data.","authors":"Yepeng Huang, Xiaorui Su, Varun Ullanat, Ivy Liang, Lindsay Clegg, Damilola Olabode, Nicholas Ho, Bino John, Megan Gibbs, Marinka Zitnik","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Predicting clinical outcomes from preclinical data is essential for identifying safe and effective drug combinations. Current models rely on structural or target-based features to identify high-efficacy, low-toxicity drug combinations. However, these approaches fail to incorporate the multimodal data necessary for accurate, clinically-relevant predictions. Here, we introduce MADRIGAL, a multimodal AI model that learns from structural, pathway, cell viability, and transcriptomic data to predict drug combination effects across 953 clinical outcomes and 21842 compounds, including combinations of approved drugs and novel compounds in development. MADRIGAL uses a transformer bottleneck module to unify preclinical drug data modalities while handling missing data during training and inference--a major challenge in multimodal learning. It outperforms single-modality methods and state-of-the-art models in predicting adverse drug interactions. MADRIGAL performs virtual screening of anticancer drug combinations and supports polypharmacy management for type II diabetes and metabolic dysfunction-associated steatohepatitis (MASH). It identifies transporter-mediated drug interactions. MADRIGAL predicts resmetirom, the first and only FDA-approved drug for MASH, among therapies with the most favorable safety profile. It supports personalized cancer therapy by integrating genomic profiles from cancer patients. Using primary acute myeloid leukemia samples and patient-derived xenograft models, it predicts the efficacy of personalized drug combinations. Integrating MADRIGAL with a large language model allows users to describe clinical outcomes in natural language, improving safety assessment by identifying potential adverse interactions and toxicity risks. MADRIGAL provides a multimodal approach for designing combination therapies with improved predictive accuracy and clinical relevance.</p>","PeriodicalId":93888,"journal":{"name":"ArXiv","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11908363/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143652591","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":"Comprehensive Analysis of Relative Pressure Estimation Methods Utilizing 4D Flow MRI.","authors":"Brandon Hardy, Judith Zimmermann, Vincent Lechner, Mia Bonini, Julio A Sotelo, Nicholas S Burris, Daniel B Ennis, David Marlevi, David A Nordsletten","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>4D flow MRI allows for the estimation of three-dimensional relative pressure fields, providing rich pressure information, unlike catheterization and Doppler echocardiography, which provide one-dimensional pressure drops only. The accuracy of one-dimensional pressure drops derived from 4D flow has been explored in previous literature, but additional work must be done to evaluate the accuracy of three-dimensional relative pressure fields. This work presents an analysis of three state-of-the-art relative pressure estimators: virtual Work-Energy Relative Pressure (<i>v</i>WERP), the Pressure Poisson Estimator (PPE), and the Stokes Estimator (STE). Spatiotemporal behavior and sensitivity to noise were determined in silico. Estimators were validated with a type B aortic dissection (TBAD) flow phantom with varying tear geometry and an array of twelve catheter pressure measurements. Finally, the performance of each estimator was evaluated across eight patient cases. In silico pressure field errors were lower in STE compared to PPE, although PPE pressures were less affected by noise. High velocity gradients and low spatial resolution contributed most significantly to local variations in 3D error fields. Low temporal resolution leads to highly transient peak pressure events being averaged, systematically underestimating peak pressures. In the flow phantom analysis, <i>v</i>WERP was the most accurate method, followed by STE and PPE. Each pressure estimator strongly correlated with ground truth pressure values despite the tendency to underestimate peak pressures. Patient case results demonstrated that the pressure estimators could be feasibly integrated into a clinical workflow.</p>","PeriodicalId":93888,"journal":{"name":"ArXiv","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11908371/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143652570","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":"A Phylogenetic Approach to Genomic Language Modeling.","authors":"Carlos Albors, Jianan Canal Li, Gonzalo Benegas, Chengzhong Ye, Yun S Song","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Genomic language models (gLMs) have shown mostly modest success in identifying evolutionarily constrained elements in mammalian genomes. To address this issue, we introduce a novel framework for training gLMs that explicitly models nucleotide evolution on phylogenetic trees using multispecies whole-genome alignments. Our approach integrates an alignment into the loss function during training but does not require it for making predictions, thereby enhancing the model's applicability. We applied this framework to train PhyloGPN, a model that excels at predicting functionally disruptive variants from a single sequence alone and demonstrates strong transfer learning capabilities.</p>","PeriodicalId":93888,"journal":{"name":"ArXiv","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11908359/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143652554","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":"Measurement noise scaling laws for cellular representation learning.","authors":"Gokul Gowri, Peng Yin, Allon M Klein","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Deep learning scaling laws predict how performance improves with increased model and dataset size. Here we identify measurement noise in data as another performance scaling axis, governed by a distinct logarithmic law. We focus on representation learning models of biological single cell genomic data, where a dominant source of measurement noise is due to molecular undersampling. We introduce an information-theoretic metric for cellular representation model quality, and find that it scales with sampling depth. A single quantitative relationship holds across several model types and across several datasets. We show that the analytical form of this relationship can be derived from a simple Gaussian noise model, which in turn provides an intuitive interpretation for the scaling law. Finally, we show that the same relationship emerges in image classification models with respect to two types of imaging noise, suggesting that measurement noise scaling may be a general phenomenon. Scaling with noise can serve as a guide in generating and curating data for deep learning models, particularly in fields where measurement quality can vary dramatically between datasets.</p>","PeriodicalId":93888,"journal":{"name":"ArXiv","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11908368/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143652577","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":"Metric-Guided Conformal Bounds for Probabilistic Image Reconstruction.","authors":"Matt Y Cheung, Tucker J Netherton, Laurence E Court, Ashok Veeraraghavan, Guha Balakrishnan","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Modern deep learning reconstruction algorithms generate impressively realistic scans from sparse inputs, but can often produce significant inaccuracies. This makes it difficult to provide statistically guaranteed claims about the true state of a subject from scans reconstructed by these algorithms. In this study, we propose a framework for computing provably valid prediction bounds on claims derived from probabilistic black-box image reconstruction algorithms. The key insights behind our framework are to represent reconstructed scans with a derived clinical metric of interest, and to calibrate bounds on the ground truth metric with conformal prediction (CP) using a prior calibration dataset. These bounds convey interpretable feedback about the subject's state, and can also be used to retrieve nearest-neighbor reconstructed scans for visual inspection. We demonstrate the utility of this framework on sparse-view computed tomography (CT) for fat mass quantification and radiotherapy planning tasks. Results show that our framework produces bounds with better semantical interpretation than conventional pixel-based bounding approaches. Furthermore, we can flag dangerous outlier reconstructions that look plausible but have statistically unlikely metric values.</p>","PeriodicalId":93888,"journal":{"name":"ArXiv","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11071610/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140853860","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":"MRI super-resolution reconstruction using efficient diffusion probabilistic model with residual shifting.","authors":"Mojtaba Safari, Shansong Wang, Zach Eidex, Qiang Li, Erik H Middlebrooks, David S Yu, Xiaofeng Yang","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Objective: </strong>MRI offers superior soft-tissue contrast yet suffers from long acquisition times that can induce patient discomfort and motion artifacts. Super-resolution (SR) methods reconstruct high-resolution (HR) images from low-resolution (LR) scans, but diffusion models typically require numerous sampling steps, hindering real-time use. Here, we introduce a residual error-shifting strategy that reduce sampling steps without compromising anatomical fidelity, thereby improving MRI SR for clinical deployment.</p><p><strong>Approach: </strong>We propose a novel diffusion-based SR framework called Res-SRDiff, which integrates residual error shifting into the forward diffusion process. This approach enables efficient HR image reconstruction by aligning the degraded HR image distribution with the LR image distribution. Our model was evaluated on two MRI datasets: ultra-high-field brain T1 MP2RAGE maps and T2-weighted prostate images. We compared Res-SRDiff against established methods, including Bicubic, Pix2pix, CycleGAN, and a conventional denoising diffusion probabilistic model with vision transformer backbone (TM-DDPM), using quantitative metrics such as peak signal-to-noise ratio (PSNR), structural similarity index (SSIM), gradient magnitude similarity deviation (GMSD), and learned perceptual image patch similarity (LPIPS).</p><p><strong>Main results: </strong>Res-SRDiff significantly outperformed all comparative methods in terms of PSNR, SSIM, and GMSD across both datasets, with statistically significant improvements ( <math><mrow><mi>p</mi></mrow> </math> -values ≪ 0.05). The model achieved high-fidelity image restoration with only four sampling steps, drastically reducing computational time to under one second per slice, which is substantially faster than conventional TM-DDPM with around 20 seconds per slice. Qualitative analyses further demonstrated that Res-SRDiff effectively preserved fine anatomical details and lesion morphology in both brain and pelvic MRI images.</p><p><strong>Significance: </strong>Our findings show that Res-SRDiff is an efficient and accurate MRI SR method, markedly improving computational efficiency and image quality. By integrating residual error shifting into the diffusion process, it allows for rapid and robust HR image reconstruction, enhancing clinical MRI workflows and advancing medical imaging research. The source at: https://github.com/mosaf/Res-SRDiff.</p>","PeriodicalId":93888,"journal":{"name":"ArXiv","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11908366/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143652579","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":"Penalized Principal Component Analysis Using Smoothing.","authors":"Rebecca M Hurwitz, Georg Hahn","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Principal components computed via PCA (principal component analysis) are traditionally used to reduce dimensionality in genomic data or to correct for population stratification. In this paper, we explore the penalized eigenvalue problem (PEP) which reformulates the computation of the first eigenvector as an optimization problem and adds an $L_1$ penalty constraint to enforce sparseness of the solution. The contribution of our article is threefold. First, we extend PEP by applying smoothing to the original LASSO-type $L_1$ penalty. This allows one to compute analytical gradients which enable faster and more efficient minimization of the objective function associated with the optimization problem. Second, we demonstrate how higher order eigenvectors can be calculated with PEP using established results from singular value decomposition (SVD). Third, we present four experimental studies to demonstrate the usefulness of the smoothed penalized eigenvectors. Using data from the 1000 Genomes Project dataset, we empirically demonstrate that our proposed smoothed PEP allows one to increase numerical stability and obtain meaningful eigenvectors. We also employ the penalized eigenvector approach in two additional real data applications (computation of a polygenic risk score and clustering), demonstrating that exchanging the penalized eigenvectors for their smoothed counterparts can increase prediction accuracy in polygenic risk scores and enhance discernibility of clusterings. Moreover, we compare our proposed smoothed PEP to seven state-of-the-art algorithms for sparse PCA and evaluate the accuracy of the obtained eigenvectors, their support recovery, and their runtime.</p>","PeriodicalId":93888,"journal":{"name":"ArXiv","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10557800/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41164740","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-Attention-Based Contextual Modulation Improves Neural System Identification.","authors":"Isaac Lin, Tianye Wang, Shang Gao, Shiming Tang, Tai Sing Lee","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Convolutional neural networks (CNNs) have been shown to be state-of-the-art models for visual cortical neurons. Cortical neurons in the primary visual cortex are sensitive to contextual information mediated by extensive horizontal and feedback connections. Standard CNNs integrate global contextual information to model contextual modulation via two mechanisms: successive convolutions and a fully connected readout layer. In this paper, we find that self-attention (SA), an implementation of non-local network mechanisms, can improve neural response predictions over parameter-matched CNNs in two key metrics: tuning curve correlation and peak tuning. We introduce peak tuning as a metric to evaluate a model's ability to capture a neuron's top feature preference. We factorize networks to assess each context mechanism, revealing that information in the local receptive field is most important for modeling overall tuning, but surround information is critically necessary for characterizing the tuning peak. We find that self-attention can replace posterior spatial-integration convolutions when learned incrementally, and is further enhanced in the presence of a fully connected readout layer, suggesting that the two context mechanisms are complementary. Finally, we find that decomposing receptive field learning and contextual modulation learning in an incremental manner may be an effective and robust mechanism for learning surround-center interactions.</p>","PeriodicalId":93888,"journal":{"name":"ArXiv","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11888551/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143588494","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":"A Deep Learning Approach to Multi-Fiber Parameter Estimation and Uncertainty Quantification in Diffusion MRI.","authors":"William Consagra, Lipeng Ning, Yogesh Rathi","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Diffusion MRI (dMRI) is the primary imaging modality used to study brain microstructure in vivo. Reliable and computationally efficient parameter inference for common dMRI biophysical models is a challenging inverse problem, due to factors such as variable dimensionalities (reflecting the unknown number of distinct white matter fiber populations in a voxel), low signal-to-noise ratios, and non-linear forward models. These challenges have led many existing methods to use biologically implausible simplified models to stabilize estimation, for instance, assuming shared microstructure across all fiber populations within a voxel. In this work, we introduce a novel sequential method for multi-fiber parameter inference that decomposes the task into a series of manageable subproblems. These subproblems are solved using deep neural networks tailored to problem-specific structure and symmetry, and trained via simulation. The resulting inference procedure is largely amortized, enabling scalable parameter estimation and uncertainty quantification across all model parameters. Simulation studies and real imaging data analysis using the Human Connectome Project (HCP) demonstrate the advantages of our method over standard alternatives. In the case of the standard model of diffusion, our results show that under HCP-like acquisition schemes, estimates for extra-cellular parallel diffusivity are highly uncertain, while those for the intra-cellular volume fraction can be estimated with relatively high precision.</p>","PeriodicalId":93888,"journal":{"name":"ArXiv","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11888552/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143588834","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}