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Digital pathology-based prognostic model for hepatocellular carcinoma: Integrating pathomics signatures with clinical parameters for recurrence prediction and biological interpretation 基于病理的肝细胞癌数字预后模型:将病理特征与复发预测和生物学解释的临床参数相结合。
IF 4.8 2区 医学 Q1 COMPUTER SCIENCE, INTERDISCIPLINARY APPLICATIONS Pub Date : 2025-11-27 DOI: 10.1016/j.cmpb.2025.109180
Qi Wang , Yuxi Huang , Yu Zhang , Yu Zhu , Peng Hu , Yongfu Xu , Zhen-yu Jiang , Long Liu , Shao-wei Li

Background

Hepatocellular carcinoma (HCC) remains a therapeutic challenge due to high post-resection recurrence rates and heterogeneous outcomes. We developed and validated a digital pathology-based prognostic model combining pathomics signatures with clinical parameters to predict recurrence and elucidate biological mechanisms.

Methods

In this multicenter retrospective study, 294 HCC patients (training set: n = 198; validation set: n = 96) undergoing curative hepatectomy were analyzed. Pathomics features were quantitatively extracted from H&E-stained whole-slide images. Predictive modeling incorporated machine learning approaches (DT, KNN, LASSO, NB, RF, SVM) with clinical variables. Model performance was evaluated through ROC analysis, calibration, and decision curve analysis. Biological interpretation leveraged TCGA transcriptomic data analyzed via GSEA and WGCNA.

Results

Tumor and peri‑tumor pathomics parameters showed some complementarity in the prediction of HCC recurrence. The combined LASSO-based model showed the best predictive efficacy, with AUCs of 0.850 and 0.807 in the training and validation sets, respectively. The integrated pathomics-clinical model achieved AUCs of 0.893 and 0.860 in training and validation sets. Bioinformatics analysis suggested that the pathomics was correlated with the tumor immune microenvironment, as verified by multiple immunofluorescence staining of the validation set.

Conclusion

This study establishes a robust digital pathology framework that not only improves HCC recurrence prediction beyond conventional biomarkers but also provides mechanistic insights into tumor-immune crosstalk.
背景:肝细胞癌(HCC)仍然是一个治疗挑战,由于高术后复发率和异质性的结果。我们开发并验证了一种基于病理的数字预后模型,该模型结合了病理特征和临床参数来预测复发并阐明生物学机制。方法:在这项多中心回顾性研究中,对294例行根治性肝切除术的HCC患者(训练组198例,验证组96例)进行分析。从h&e染色的全片图像中定量提取病理特征。预测建模结合了机器学习方法(DT、KNN、LASSO、NB、RF、SVM)和临床变量。通过ROC分析、校正和决策曲线分析来评估模型的性能。生物解释利用了通过GSEA和WGCNA分析的TCGA转录组数据。结果:肿瘤和肿瘤周围病理参数在预测HCC复发方面具有一定的互补性。基于lasso的联合模型预测效果最好,训练集和验证集的auc分别为0.850和0.807。综合病理-临床模型在训练集和验证集的auc分别为0.893和0.860。生物信息学分析表明,病理与肿瘤免疫微环境相关,验证组多次免疫荧光染色证实。结论:该研究建立了一个强大的数字病理学框架,不仅可以提高HCC复发预测,而且可以提供肿瘤免疫串扰的机制见解。
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引用次数: 0
ElasticMorph: Plug-and-play second-order elastic regularization for medical image registration ElasticMorph:即插即用的二阶弹性正则化医学图像配准。
IF 4.8 2区 医学 Q1 COMPUTER SCIENCE, INTERDISCIPLINARY APPLICATIONS Pub Date : 2025-11-27 DOI: 10.1016/j.cmpb.2025.109182
Zhaoxi Lin, Shan Jiang, Zeyang Zhou, Zhiyong Yang, Yuhua Li

Background and Objective:

Deformable image registration is crucial for many clinical applications, but current learning-based methods often rely on simple smoothness losses. This can produce physically implausible deformations, such as tissue folding, and creates a trade-off between registration accuracy and anatomical correctness. The objective of this study is to develop and validate a novel, physics-informed regularizer that simultaneously improves both the accuracy and physical plausibility of learning-based registration with negligible computational overhead.

Methods:

We propose ElasticMorph, a plug-and-play loss function derived from the Navier–Cauchy equation. This regularizer penalizes both curvature and divergence in the deformation field. We derive an approximation based, measure theoretic bound under small strain assumptions, which links the elastic residual to an upper bound on the number of negative Jacobian voxels. This gives a principled and differentiable surrogate for folding control. The method was evaluated on two public brain MRI benchmarks (IXI and LPBA-40) by integrating it into four state-of-the-art CNN and transformer backbones. Performance was quantified using the Dice Similarity Coefficient (DSC) and the percentage of negative Jacobians (%negJ), with statistical significance assessed via paired t-tests.

Results:

Across all tested backbones and datasets, ElasticMorph consistently improved registration accuracy, increasing the mean DSC by 0.56–4.92 %. Concurrently, it suppressed folding artifacts, reducing the %negJ by 24%–42%. This was achieved with a minimal increase in training time 8% and memory 15%, and no cost at inference. Ablation studies confirmed that the combined curvature-divergence loss outperformed either component alone. A hyperparameter sweep revealed a broad optimal range, with folding artifacts monotonically decreasing as regularization strength increased, consistent with our theoretical proof.

Conclusions:

Enforcing second-order linear elasticity offers a robust and computationally efficient strategy to overcome the limitations of conventional regularizers. ElasticMorph provides a practical, principled, and plug-and-play solution for developing more accurate and physically plausible registration models, holding significant potential for improving the reliability of downstream biomedical image analysis tasks. The code will be made publicly available.
背景和目的:可变形图像配准对于许多临床应用至关重要,但目前基于学习的方法通常依赖于简单的平滑度损失。这可能会产生物理上难以置信的变形,如组织折叠,并在注册精度和解剖正确性之间产生权衡。本研究的目的是开发和验证一种新颖的、物理信息的正则化器,该正则化器同时提高了基于学习的配准的准确性和物理合理性,而计算开销可以忽略不计。方法:我们提出了一种基于Navier-Cauchy方程的即插即用损失函数ElasticMorph。这个正则化器惩罚变形场中的曲率和散度。我们在小应变假设下推导了一个基于近似的测量理论界,它将弹性残差与负雅可比体素数的上界联系起来。这为折叠控制提供了一个原则性的和可微的替代。将该方法集成到四个最先进的CNN和变压器骨干网中,在两个公共脑MRI基准(IXI和lbaa -40)上进行了评估。使用骰子相似系数(DSC)和负雅可比矩阵百分比(%negJ)对性能进行量化,通过配对t检验评估统计学显著性。结果:在所有测试的骨干网和数据集中,ElasticMorph持续提高了配准精度,将平均DSC提高了0.56- 4.92%。同时,它抑制折叠伪影,使%negJ降低24%-42%。这是在训练时间≤8%和内存≤15%的最小增加下实现的,并且在推理上没有成本。消融研究证实,联合曲率-散度损失优于单独的任何一种成分。超参数扫描显示了较宽的最优范围,随着正则化强度的增加,折叠伪影单调减少,与我们的理论证明一致。结论:加强二阶线性弹性提供了一种鲁棒和计算效率高的策略,以克服传统正则化器的局限性。ElasticMorph提供了一个实用的、有原则的、即插即用的解决方案,用于开发更准确、物理上更合理的配准模型,在提高下游生物医学图像分析任务的可靠性方面具有巨大的潜力。该准则将向公众开放。
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引用次数: 0
The added value of radiomic analysis for predicting spontaneous preterm birth in the first trimester 放射组学分析预测妊娠早期自发性早产的附加价值
IF 4.8 2区 医学 Q1 COMPUTER SCIENCE, INTERDISCIPLINARY APPLICATIONS Pub Date : 2025-11-26 DOI: 10.1016/j.cmpb.2025.109181
William Cancino , Carlos Hernan Becerra-Mojica , Said Pertuz

Background and Objective:

Preterm birth (PTB) is a public health problem. Researchers have worked to identify ways to detect women at risk for PTB early in pregnancy. Although existing biomarkers allow some women to be detected in the second trimester, detection in the first trimester is warranted to initiate earlier interventions. This study aims to explore the added value of radiomic analysis of transvaginal ultrasound (TVUS) images in the construction of first-trimester risk assessment models for predicting spontaneous preterm birth (sPTB).

Methods:

A retrospective cohort study was conducted including pregnant women who attended their screening ultrasound examination between 11+0 and 13+6 weeks. Data on medical history (MH), cervical length (CL), and cervical consistency index (CCI) were collected, along with TVUS images. These images were subjected to a computerized radiomic analysis to extract features, which were used to train different machine learning models incorporating a feature selection process. The area under the receiver operating characteristic curve (AUC) with 95% confidence intervals (CI) was used to evaluate the models’ performance in predicting sPTB.

Results:

A total of 253 pregnant women were included in the study, where 225 had a term birth and 28 had a sPTB. In sPTB prediction, MH, CL, and CCI obtained AUCs of 0.68 (95% CI, 0.56–0.79), 0.61 (95% CI, 0.48–0.73) and 0.67 (95% CI, 0.55–0.79), respectively. Among the evaluated machine learning models, logistic regression achieved the highest AUC and was therefore used to build the radiomic feature–based model (RF), which reached an AUC of 0.67 (95% CI, 0.56–0.76). When combining RF with MH and CCI, AUCs of 0.73 (95% CI, 0.63–0.82) and 0.74 (95% CI, 0.64–0.83) were achieved, respectively. The best performance was obtained by combining RF with both MH and CCI, reaching an AUC of 0.76 (95% CI, 0.68–0.84).

Conclusion:

The performance of the models improved by adding radiomic features, highlighting the potential of radiomic analysis for sPTB prediction in the first trimester.
背景与目的:早产(PTB)是一个公共卫生问题。研究人员一直致力于寻找在怀孕早期发现妇女患肺结核风险的方法。虽然现有的生物标志物允许一些妇女在妊娠中期被检测到,但在妊娠早期检测是有必要进行早期干预的。本研究旨在探讨经阴道超声(TVUS)影像放射组学分析在构建预测自发性早产(sPTB)的妊娠早期风险评估模型中的附加价值。方法:采用回顾性队列研究,纳入11+0 ~ 13+6周接受超声筛查的孕妇。收集病史(MH)、宫颈长度(CL)、宫颈一致性指数(CCI)数据以及TVUS图像。这些图像经过计算机放射学分析以提取特征,这些特征用于训练包含特征选择过程的不同机器学习模型。采用受试者工作特征曲线下面积(AUC)和95%置信区间(CI)来评价模型预测sPTB的效果。结果:共有253名孕妇参与了这项研究,其中225名是足月分娩,28名患有sPTB。在sPTB预测中,MH、CL和CCI的auc分别为0.68 (95% CI, 0.56-0.79)、0.61 (95% CI, 0.48-0.73)和0.67 (95% CI, 0.55-0.79)。在评估的机器学习模型中,逻辑回归获得了最高的AUC,因此用于构建基于放射学特征的模型(RF), AUC达到0.67 (95% CI, 0.56-0.76)。当RF与MH和CCI联合使用时,auc分别为0.73 (95% CI, 0.63-0.82)和0.74 (95% CI, 0.64-0.83)。RF与MH和CCI联合使用效果最佳,AUC为0.76 (95% CI为0.68-0.84)。结论:通过添加放射组学特征,模型的性能得到了提高,突出了放射组学分析在早期妊娠期sPTB预测中的潜力。
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引用次数: 0
Adapt or specialize? A comprehensive evaluation of adapted SAM versus task-specific CNNs for fetal abdominal segmentation 适应还是专业化?对胎儿腹部分割的适应性SAM与任务特异性cnn的综合评估
IF 4.8 2区 医学 Q1 COMPUTER SCIENCE, INTERDISCIPLINARY APPLICATIONS Pub Date : 2025-11-26 DOI: 10.1016/j.cmpb.2025.109178
Maria Chiara Fiorentino , Lorenzo Federici , Alessandro Pietro La Camera , Enrico Gianluca Caiani

Background:

The fetal abdomen is crucial in prenatal screening, offering key insights into fetal growth and congenital anomalies. However, segmenting internal abdominal structures in ultrasound (US) remains challenging due to anatomical variability, overlapping organs, and low contrast. While CNN-based models have shown strong performance in fetal head analysis, most existing methods focus on biometric measurements (e.g., head or abdominal circumference), leaving internal abdominal organ segmentation largely underexplored. Recently, foundation models like the Segment Anything Model (SAM) have emerged as flexible alternatives, enabling zero- or few-shot segmentation. Yet, their performance on fetal US remains poorly understood, and the need for adaptation is still an open question.

Methods:

We compare two segmentation strategies: (1) task-specific CNNs, including UNet, Attention UNet, nnUNet, DeepLabv3+, and their focal-loss variants; and (2) adapted SAM-based models. The latter includes zero-shot variants (SAMPoint, SAMBBox), pre-trained models (SAM Med2DBBox, MedSAMBBox), and adapted configurations, including lightweight fine-tuned models (SAM-LoRA, MedSAM-FrozenEncoder) and SAM Med2D variants with adapted layers. Experiments are conducted on a curated dataset of fetal abdominal US images with manual segmentations of the liver, stomach, artery, and umbilical vein. Performance is evaluated using Dice Similarity Coefficient, Intersection over Union, and precision. Statistical significance is assessed via pairwise Friedman chi-square tests.

Results & Conclusions:

Zero-shot SAM variants performed poorly, particularly on small or low-contrast structures. In contrast, adapted SAM models consistently outperformed CNNs, reaching DSC scores up to 0.90 (liver) and 0.80 (artery). Prompt-based interaction enables semi-automated, human-in-the-loop workflows, supporting clinical applicability.
背景:胎儿腹部在产前筛查中是至关重要的,为胎儿生长和先天性异常提供了关键的见解。然而,由于解剖变异、器官重叠和低对比度,在超声(US)中分割腹部内部结构仍然具有挑战性。虽然基于cnn的模型在胎儿头部分析中表现出色,但大多数现有方法都侧重于生物特征测量(例如头部或腹部围),而对腹部内部器官分割的探索很大程度上不足。最近,像分段任意模型(SAM)这样的基础模型已经作为灵活的替代方案出现,可以实现零次或几次分段。然而,他们对胎儿US的表现仍然知之甚少,适应的必要性仍然是一个悬而未决的问题。方法:我们比较了两种分割策略:(1)针对特定任务的cnn,包括UNet、Attention UNet、nnUNet、DeepLabv3+及其焦点丢失变体;(2)适应的基于sam的模型。后者包括零射击变体(SAMPoint, SAMBBox),预训练模型(SAM Med2DBBox, MedSAMBBox)和适应配置,包括轻量级微调模型(SAM- lora, MedSAM-FrozenEncoder)和具有适应层的SAM Med2D变体。实验是在一个精心策划的胎儿腹部US图像数据集上进行的,该数据集具有人工分割的肝脏、胃、动脉和脐静脉。性能评估使用骰子相似系数,交集超过联合,和精度。通过两两Friedman卡方检验评估统计显著性。结果&结论:零射击SAM变体表现不佳,特别是在小或低对比度结构上。相比之下,适应性SAM模型的表现一直优于cnn, DSC得分高达0.90(肝脏)和0.80(动脉)。基于提示的交互实现了半自动化、人在循环的工作流程,支持临床应用。
{"title":"Adapt or specialize? A comprehensive evaluation of adapted SAM versus task-specific CNNs for fetal abdominal segmentation","authors":"Maria Chiara Fiorentino ,&nbsp;Lorenzo Federici ,&nbsp;Alessandro Pietro La Camera ,&nbsp;Enrico Gianluca Caiani","doi":"10.1016/j.cmpb.2025.109178","DOIUrl":"10.1016/j.cmpb.2025.109178","url":null,"abstract":"<div><h3>Background:</h3><div>The fetal abdomen is crucial in prenatal screening, offering key insights into fetal growth and congenital anomalies. However, segmenting internal abdominal structures in ultrasound (US) remains challenging due to anatomical variability, overlapping organs, and low contrast. While CNN-based models have shown strong performance in fetal head analysis, most existing methods focus on biometric measurements (e.g., head or abdominal circumference), leaving internal abdominal organ segmentation largely underexplored. Recently, foundation models like the Segment Anything Model (SAM) have emerged as flexible alternatives, enabling zero- or few-shot segmentation. Yet, their performance on fetal US remains poorly understood, and the need for adaptation is still an open question.</div></div><div><h3>Methods:</h3><div>We compare two segmentation strategies: (1) task-specific CNNs, including UNet, Attention UNet, nnUNet, DeepLabv3+, and their focal-loss variants; and (2) adapted SAM-based models. The latter includes zero-shot variants (SAMPoint, SAMBBox), pre-trained models (SAM Med2DBBox, MedSAMBBox), and adapted configurations, including lightweight fine-tuned models (SAM-LoRA, MedSAM-FrozenEncoder) and SAM Med2D variants with adapted layers. Experiments are conducted on a curated dataset of fetal abdominal US images with manual segmentations of the liver, stomach, artery, and umbilical vein. Performance is evaluated using Dice Similarity Coefficient, Intersection over Union, and precision. Statistical significance is assessed via pairwise Friedman chi-square tests.</div></div><div><h3>Results &amp; Conclusions:</h3><div>Zero-shot SAM variants performed poorly, particularly on small or low-contrast structures. In contrast, adapted SAM models consistently outperformed CNNs, reaching DSC scores up to 0.90 (liver) and 0.80 (artery). Prompt-based interaction enables semi-automated, human-in-the-loop workflows, supporting clinical applicability.</div></div>","PeriodicalId":10624,"journal":{"name":"Computer methods and programs in biomedicine","volume":"275 ","pages":"Article 109178"},"PeriodicalIF":4.8,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145600477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
An uncertainty-aware dynamic decision framework for progressive multi-omics integration in classification tasks 分类任务中渐进式多组学集成的不确定性感知动态决策框架。
IF 4.8 2区 医学 Q1 COMPUTER SCIENCE, INTERDISCIPLINARY APPLICATIONS Pub Date : 2025-11-26 DOI: 10.1016/j.cmpb.2025.109179
Nan Mu , Hongbo Yang , Chen Zhao

Background and Objective

High-throughput multi-omics technologies offer significant potential for early disease diagnosis by capturing the complex interplay of molecular layers. However, two challenges hinder their practical application: First, single-omics approaches often miss the coordinated molecular interactions essential to disease understanding. Second, the high cost of comprehensive multi-omics profiling may lead to unnecessary resource use. To address these limitations, we propose an uncertainty-aware, multi-view dynamic decision framework that enhances classification accuracy while reducing testing costs.

Methodology

At the single-omics level, we incorporate subjective logic into neural network outputs, using refined activation functions to generate Dirichlet distribution parameters. This enables simultaneous estimation of belief masses (class-wise support) and uncertainty mass (prediction confidence). At the multi-omics level, we fuse complementary omics modalities via Dempster-Shafer theory to improve diagnostic accuracy and robustness. A dynamic decision mechanism incrementally integrates omics views for each patient, guided by real-time uncertainty: additional data are introduced only if prediction confidence fails to meet a predefined threshold, enabling individualized and efficient decision-making.

Results and Conclusion

We evaluate our approach on four benchmark multi-omics datasets, i.e., ROSMAP, LGG, BRCA, and KIPAN. In three datasets, over 50 % of cases achieved accurate classification using a single omics modality, effectively reducing redundant testing. Meanwhile, our method maintains diagnostic performance comparable to full-omics models and preserves essential biological insights. This framework introduces a novel 'on-demand testing' paradigm into precision medicine, enabling intelligent resource allocation and reducing healthcare costs, which is especially valuable in resource-limited clinical environments.
背景和目的:高通量多组学技术通过捕获分子层的复杂相互作用,为早期疾病诊断提供了巨大的潜力。然而,两个挑战阻碍了它们的实际应用:首先,单组学方法经常错过对疾病理解至关重要的协调分子相互作用。其次,综合多组学分析的高成本可能导致不必要的资源使用。为了解决这些限制,我们提出了一个不确定性感知的多视图动态决策框架,该框架在降低测试成本的同时提高了分类精度。方法:在单组学层面,我们将主观逻辑纳入神经网络输出,使用精炼的激活函数生成狄利克雷分布参数。这使得同时估计信念质量(类支持)和不确定性质量(预测置信度)成为可能。在多组学水平,我们通过Dempster-Shafer理论融合互补组学模式,以提高诊断准确性和稳健性。动态决策机制以实时不确定性为指导,逐步整合每个患者的组学视图:只有在预测置信度未能达到预定义阈值时才引入额外的数据,从而实现个性化和高效的决策。结果和结论:我们在ROSMAP、LGG、BRCA和KIPAN四个基准多组学数据集上评估了我们的方法。在三个数据集中,超过50%的病例使用单一组学模式实现了准确分类,有效减少了冗余测试。同时,我们的方法保持了与全组学模型相当的诊断性能,并保留了基本的生物学见解。该框架为精准医疗引入了一种新颖的“按需测试”范式,实现了智能资源分配并降低了医疗成本,这在资源有限的临床环境中尤其有价值。
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引用次数: 0
MDM-DTA: Message Passing Neural Network with molecular descriptors and Mixture of Experts for drug–target affinity prediction MDM-DTA:基于分子描述符和混合专家的消息传递神经网络用于药物靶点亲和力预测。
IF 4.8 2区 医学 Q1 COMPUTER SCIENCE, INTERDISCIPLINARY APPLICATIONS Pub Date : 2025-11-21 DOI: 10.1016/j.cmpb.2025.109163
Yang Dai , Xiaoyu Tan , Haoyu Wang , Gengchen Ma , Yujie Xiong , Xihe Qiu

Background and Objective:

Drug–target affinity (DTA) prediction is a pivotal task in computational drug discovery, enabling the estimation of binding affinities between small molecules and their target proteins. This process is essential for reducing the costs, development time, and risks inherent in traditional drug development pipelines. Current DTA prediction models primarily rely on separate extraction and concatenation of drug and protein features. However, these models often fail to account for the complex semantic relationships within protein sequences, which limits their ability to accurately predict affinity.

Methods:

In response to these challenges, we propose MDM-DTA, a novel framework leveraging a Mixture of Experts (MoE) strategy to integrate diverse molecular and protein representations. For drug representation, MDM-DTA utilizes molecular graphs, which are processed via Message Passing Neural Networks (MPNNs), alongside molecular descriptors that are passed through a three-layer convolutional neural network (CNN). Protein features are extracted using a deep convolutional network enhanced with Squeeze-and-Excitation (SE) mechanisms to capture inter-channel dependencies. Furthermore, protein sequence semantics are encoded through pre-trained embeddings from a knowledge-guided Bidirectional Encoder Representations from Transformers (BERT) model and the Evolutionary Scale Modeling 2 (ESM2) model, enabling the model to capture contextual relationships within protein sequences.

Results:

Extensive experiments on three benchmark datasets demonstrate that MDM-DTA consistently outperforms state-of-the-art models of similar complexity in terms of predictive accuracy. The incorporation of both structural and semantic features significantly enhances the model’s ability to predict drug–target binding affinities, highlighting the importance of a multi-modal representation approach.

Conclusions:

The proposed MDM-DTA framework effectively integrates both molecular and semantic protein representations, providing superior performance in DTA prediction tasks. The results underscore the potential of MDM-DTA to improve the accuracy of computational drug discovery models, facilitating the identification of novel drug candidates and advancing the field of in silico drug development.
背景与目的:药物靶标亲和力(drug -target affinity, DTA)预测是计算药物发现的关键任务,它能够估计小分子与其靶蛋白之间的结合亲和力。这一过程对于减少成本、开发时间和传统药物开发管道中固有的风险至关重要。目前的DTA预测模型主要依赖于药物和蛋白质特征的分离提取和串联。然而,这些模型往往不能解释蛋白质序列中复杂的语义关系,这限制了它们准确预测亲和力的能力。方法:为了应对这些挑战,我们提出了MDM-DTA,这是一个利用混合专家(MoE)策略来整合不同分子和蛋白质表征的新框架。对于药物表示,MDM-DTA利用通过消息传递神经网络(MPNNs)处理的分子图,以及通过三层卷积神经网络(CNN)传递的分子描述符。蛋白质特征提取使用深度卷积网络增强与挤压和激励(SE)机制,以捕获通道间的依赖关系。此外,蛋白质序列语义通过知识导向的双向编码器表示(BERT)模型和进化尺度建模2 (ESM2)模型的预训练嵌入进行编码,使该模型能够捕获蛋白质序列中的上下文关系。结果:在三个基准数据集上进行的大量实验表明,MDM-DTA在预测准确性方面始终优于类似复杂性的最先进模型。结构和语义特征的结合显著增强了模型预测药物-靶标结合亲和力的能力,突出了多模态表示方法的重要性。结论:所提出的MDM-DTA框架有效地整合了分子和语义蛋白质表示,在DTA预测任务中提供了优越的性能。这些结果强调了MDM-DTA在提高计算药物发现模型的准确性,促进新候选药物的识别和推进计算机药物开发领域方面的潜力。
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引用次数: 0
Novel machine learning framework for multidimensional biological age estimation reveals heterogeneous aging of organ systems 多维生物年龄估计的新机器学习框架揭示了器官系统的异质老化
IF 4.8 2区 医学 Q1 COMPUTER SCIENCE, INTERDISCIPLINARY APPLICATIONS Pub Date : 2025-11-20 DOI: 10.1016/j.cmpb.2025.109176
Qi Yu , Lijuan Da , Qian Ma , Yushu Huang , Yue Dong , Yuan Liu , Xiaoyu Li , Xifeng Wu , Zilin Li , Wenyuan Li

Objective

Existing biological age (BA) models often oversimplify aging’s complexity, offering single-dimensional metrics. However, these fail to capture the critical heterogeneity of aging across organs.. This study aims to develop a machine learning-based unified framework to assess and interpret multi-organ biological aging comprehensively.

Method

Using data from UK Biobank participants, we trained and integrated organ-specific BA estimates to assess multidimensional BA within an ensemble learning framework, and uncover distinct aging patterns.

Result

Our Fusion BA (an overall estimation of BA) was significantly correlated with chronological age (CA) (mean absolute error (MAE): 4.473 years; Pearson correlation: 0.718, P < 0.01). Accelerated Fusion BA derived from the ensemble model (contrast between Fusion BA and CA) predicted 10-year mortality (HR=1.504, 95 % CI: 1.438–1.574). Organ-specific BA correlated with organ disease risk and effectively captured distinct aging patterns.

Conclusion

This framework enables systemic and organ-specific aging assessment, provides actionable tools and insights for clinical risk.
现有的生物年龄(BA)模型往往过于简化了衰老的复杂性,提供了单一的指标。然而,这些未能捕捉到各器官衰老的关键异质性。本研究旨在建立一个基于机器学习的统一框架来全面评估和解释多器官生物衰老。方法使用来自UK Biobank参与者的数据,我们训练并整合了器官特异性BA估计,以在集成学习框架内评估多维BA,并揭示不同的衰老模式。结果tour Fusion BA (BA的总估计值)与实足年龄(CA)显著相关(平均绝对误差(MAE): 4.473岁;Pearson相关性:0.718,P < 0.01)。来自集合模型的加速融合BA(融合BA和CA的对比)预测10年死亡率(HR=1.504, 95% CI: 1.438-1.574)。器官特异性BA与器官疾病风险相关,并有效捕获不同的衰老模式。结论该框架可实现系统性和器官特异性衰老评估,为临床风险提供可操作的工具和见解。
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引用次数: 0
Drug repurposing through pathway perturbation dynamics: A systems biology approach for precision oncology 通过途径微扰动力学的药物再利用:精确肿瘤学的系统生物学方法。
IF 4.8 2区 医学 Q1 COMPUTER SCIENCE, INTERDISCIPLINARY APPLICATIONS Pub Date : 2025-11-20 DOI: 10.1016/j.cmpb.2025.109177
Xianbin Li , Wuxiang Ruan , Guoan Lu , Dingcheng Ban , Luming Tian , Binbin Wang , Tao Liu , Guodao Zhang , Chunping Wang , Jie Lin

Background and objective

Drug repurposing offers a cost-efficient strategy to discover new therapeutic applications for approved drugs. While current computational strategies prioritize candidates by targeting disease-related pathways, they often fail to quantitatively model pathway perturbation dynamics—a critical gap that limits mechanistic interpretability.

Methods

To address this issue, we presented PathPertDrug, a novel framework that systematically identifies cancer drug candidates by quantifying functional antagonism between drug-induced and disease-associated pathway perturbations (activation/ inhibition). By integrating drug-induced gene expression, disease-related gene expression, and pathway information, PathPertDrug evaluated pathway-level functional reversals, enabling precise prediction of drug-disease associations.

Results

Our method demonstrated superior predictive accuracy and robustness across pan-cancer benchmarks. It achieved a higher median AUROC (0.62 vs. 0.42–0.53) and a substantial improvement in AUPR (3–23 %) over existing methods. The consistent AUPR enhancement, particularly under class imbalance, underscores the robustness of our model in reliably prioritizing true positive associations. Validated by the comparative toxicogenmics database, PathPertDrug rediscovered 83 % of literature-supported cancer drugs (e.g., fulvestrant (Fulvestrant) for colorectal cancer) and predicted novel candidates (e.g., rifabutin–lung cancer).

Conclusions

This pathway-centric approach bridged mechanistic insights with translational applications, providing a paradigm shift for precision oncology drug discovery.
背景和目的:药物再利用为发现已批准药物的新治疗应用提供了一种具有成本效益的策略。虽然目前的计算策略通过针对疾病相关的途径来优先考虑候选者,但它们往往无法定量地模拟途径扰动动力学——这是一个限制机制可解释性的关键缺陷。方法:为了解决这个问题,我们提出了PathPertDrug,这是一个新的框架,通过量化药物诱导和疾病相关途径扰动(激活/抑制)之间的功能拮抗,系统地识别癌症候选药物。通过整合药物诱导的基因表达、疾病相关的基因表达和通路信息,PathPertDrug评估了通路水平的功能逆转,从而能够精确预测药物与疾病的关联。结果:我们的方法在泛癌症基准中表现出卓越的预测准确性和稳健性。与现有方法相比,该方法获得了更高的中位AUROC (0.62 vs. 0.42-0.53),并且AUPR(3- 23%)得到了显著改善。一致的AUPR增强,特别是在阶级不平衡的情况下,强调了我们的模型在可靠地优先考虑真正关联方面的稳健性。通过比较毒理学数据库的验证,PathPertDrug重新发现了83%的文献支持的癌症药物(例如,用于结直肠癌的氟维司汀(fulvestrant)),并预测了新的候选药物(例如,利法布汀-肺癌)。结论:这种以途径为中心的方法将机制见解与转化应用联系起来,为精确的肿瘤药物发现提供了范式转变。
{"title":"Drug repurposing through pathway perturbation dynamics: A systems biology approach for precision oncology","authors":"Xianbin Li ,&nbsp;Wuxiang Ruan ,&nbsp;Guoan Lu ,&nbsp;Dingcheng Ban ,&nbsp;Luming Tian ,&nbsp;Binbin Wang ,&nbsp;Tao Liu ,&nbsp;Guodao Zhang ,&nbsp;Chunping Wang ,&nbsp;Jie Lin","doi":"10.1016/j.cmpb.2025.109177","DOIUrl":"10.1016/j.cmpb.2025.109177","url":null,"abstract":"<div><h3>Background and objective</h3><div>Drug repurposing offers a cost-efficient strategy to discover new therapeutic applications for approved drugs. While current computational strategies prioritize candidates by targeting disease-related pathways, they often fail to quantitatively model pathway perturbation dynamics—a critical gap that limits mechanistic interpretability.</div></div><div><h3>Methods</h3><div>To address this issue, we presented PathPertDrug, a novel framework that systematically identifies cancer drug candidates by quantifying functional antagonism between drug-induced and disease-associated pathway perturbations (activation/ inhibition). By integrating drug-induced gene expression, disease-related gene expression, and pathway information, PathPertDrug evaluated pathway-level functional reversals, enabling precise prediction of drug-disease associations.</div></div><div><h3>Results</h3><div>Our method demonstrated superior predictive accuracy and robustness across pan-cancer benchmarks. It achieved a higher median AUROC (0.62 vs. 0.42–0.53) and a substantial improvement in AUPR (3–23 %) over existing methods. The consistent AUPR enhancement, particularly under class imbalance, underscores the robustness of our model in reliably prioritizing true positive associations. Validated by the comparative toxicogenmics database, PathPertDrug rediscovered 83 % of literature-supported cancer drugs (e.g., fulvestrant (Fulvestrant) for colorectal cancer) and predicted novel candidates (e.g., rifabutin–lung cancer).</div></div><div><h3>Conclusions</h3><div>This pathway-centric approach bridged mechanistic insights with translational applications, providing a paradigm shift for precision oncology drug discovery.</div></div>","PeriodicalId":10624,"journal":{"name":"Computer methods and programs in biomedicine","volume":"274 ","pages":"Article 109177"},"PeriodicalIF":4.8,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145602799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A multi-constituent model of thrombosis for blood-contacting medical devices 血液接触医疗器械血栓形成的多组分模型。
IF 4.8 2区 医学 Q1 COMPUTER SCIENCE, INTERDISCIPLINARY APPLICATIONS Pub Date : 2025-11-19 DOI: 10.1016/j.cmpb.2025.109158
Yuning Lin , Yuzhou Cheng , Kaiyue Yang , Kun Luo , Jianren Fan , Ru Lin , Qiang Shu

Background and objectives:

Ventricular assist devices (VADs) are currently effective clinical interventions for treating diseases related to end-stage heart failure (HF), yet hemocompatibility-related complications persist as prevalent challenges. Among them, device-induced thrombosis may lead to severe consequences such as stroke, neurological events, pump replacement, and even mortality, making it critically important to predict thrombosis accurately. The primary objective of this study is to develop a thrombosis model capable of simulating thrombus formation within VADs.

Methods:

The proposed model integrates hemodynamics, platelet activity, and the coagulation cascade, wherein the cascade products regulate platelet activation, aggregation, and stabilization. To enable simulations at the device scale while preserving essential physiological mechanisms, a reduced-order coagulation cascade model was adopted. Furthermore, the model incorporates hemodynamic-thrombus interaction while thrombus breakdown due to the shear stress clearance is under consideration.

Results:

The model was first validated in a backward-facing step (BFS) geometry to assess its applicability under separated flow conditions. In terms of volumetric evolution, the simulation followed a trend consistent with experimental data, while the thrombus length and height matched the experimental measurements closely. The model was then applied to a left ventricular assist device (VAD) to explore thrombus formation mechanisms. Simulations at different flow rates revealed consistent thrombosis on the straightener blades, while initiation sites and growth dynamics were governed by local hemodynamics, platelet activation, and stabilization.

Conclusions:

The thrombosis model developed in this study enables the investigation of thrombus formation mechanisms and the identification of potential high-risk regions within VADs under varying flow conditions. It provides a basis for future experimental validation and has potential utility for optimizing VAD design and informing patient-specific risk assessment.
背景和目的:心室辅助装置(VADs)是目前治疗终末期心力衰竭(HF)相关疾病的有效临床干预措施,但血液相容性相关并发症仍然是普遍存在的挑战。其中,器械诱发的血栓形成可能导致中风、神经系统事件、泵置换甚至死亡等严重后果,因此准确预测血栓形成至关重要。本研究的主要目的是建立一个能够模拟VADs内血栓形成的血栓形成模型。方法:该模型整合了血流动力学、血小板活性和凝血级联,其中级联产物调节血小板的活化、聚集和稳定。为了能够在设备规模上进行模拟,同时保留基本的生理机制,采用了降阶凝血级联模型。此外,该模型考虑了血流动力学-血栓相互作用,同时考虑了剪切应力清除引起的血栓破裂。结果:该模型首先在后向台阶(BFS)几何结构中进行了验证,以评估其在分离流动条件下的适用性。在体积演化方面,模拟的趋势与实验数据一致,血栓的长度和高度与实验测量值非常吻合。然后将该模型应用于左心室辅助装置(VAD)以探索血栓形成机制。不同流速下的模拟结果表明,矫直机叶片上的血栓形成是一致的,而起始位置和生长动力学受局部血流动力学、血小板活化和稳定的控制。结论:本研究建立的血栓形成模型可以研究不同血流条件下VADs内血栓形成机制和潜在高危区域的识别。它为未来的实验验证提供了基础,并具有优化VAD设计和告知患者特定风险评估的潜在效用。
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引用次数: 0
GICAF-Net: A cross-attentional graph-image fusion network for hyperspectral pathological diagnosis of FNH and HCC GICAF-Net:用于FNH和HCC高光谱病理诊断的交叉注意图形图像融合网络。
IF 4.8 2区 医学 Q1 COMPUTER SCIENCE, INTERDISCIPLINARY APPLICATIONS Pub Date : 2025-11-19 DOI: 10.1016/j.cmpb.2025.109171
Yunze Li , Haiyan Chen , Baoxian Gong , Jiankang Han , Jun Cheng , Shuai Gao , Wei Li

Background and objective

Accurate intraoperative differentiation between focal nodular hyperplasia (FNH) and hepatocellular carcinoma (HCC) remains a major clinical challenge, especially in atypical cases where conventional imaging and histopathology are constrained by turnaround time, cost, or spectral resolution. This study aims to develop a novel deep learning framework to improve the precision and efficiency of hyperspectral pathological diagnosis for liver tumors.

Methods

We propose GICAF-Net, a Graph–Image Cross-Attentional Fusion Network, designed to leverage hyperspectral imaging (HSI) for capturing fine-grained spatial–spectral information. The network employs a dual-branch architecture: (1) a residual convolutional branch for extracting pseudo-color image features, and (2) a residual graph convolutional branch for modeling topological spatial–spectral features. A Topology-Aware Cross-Attention Fusion (TACA) module enables bidirectional information exchange between the two modalities, while a multi-constraint fusion loss—combining cross-entropy, prediction confidence, and cross-modal attention consistency—enhances classification stability. A balanced hyperspectral liver tumor dataset consisting of 60 HCC and 60 FNH cases was constructed and evaluated using ten-fold cross-validation.

Results

GICAF-Net achieved an AUC of 0.9571 ± 0.0068, accuracy of 88.34 % ± 1.10 %, and F1-score of 88.32 % ± 1.11 %, outperforming state-of-the-art baseline models. Ablation experiments further validated the contributions of both the TACA module and the multi-constraint loss function in enhancing cross-modal fusion and improving classification performance.

Conclusion

The integration of graph-based spectral–structural modeling with deep visual features through cross-attention provides a powerful approach for hyperspectral pathological diagnosis. The proposed GICAF-Net demonstrates strong potential for rapid, accurate, and minimally invasive intraoperative differentiation of FNH and HCC, offering valuable clinical support in liver tumor surgery.
背景和目的:术中准确区分局灶性结节增生(FNH)和肝细胞癌(HCC)仍然是一个主要的临床挑战,特别是在常规影像学和组织病理学受周转时间、成本或光谱分辨率限制的非典型病例中。本研究旨在开发一种新的深度学习框架,以提高肝脏肿瘤高光谱病理诊断的准确性和效率。方法:我们提出了图形图像交叉注意融合网络(GICAF-Net),旨在利用高光谱成像(HSI)捕获细粒度的空间光谱信息。该网络采用双分支架构:(1)残差卷积分支用于提取伪彩色图像特征,(2)残差图卷积分支用于建模拓扑空间光谱特征。拓扑感知交叉注意融合(TACA)模块实现了两种模式之间的双向信息交换,而多约束融合损失(结合交叉熵、预测置信度和交叉模态注意一致性)增强了分类稳定性。构建了一个平衡的高光谱肝脏肿瘤数据集,包括60例HCC和60例FNH病例,并使用十倍交叉验证进行评估。结果:GICAF-Net的AUC为0.9571±0.0068,准确率为88.34%±1.10%,f1评分为88.32%±1.11%,优于目前最先进的基线模型。烧蚀实验进一步验证了TACA模块和多约束损失函数在增强跨模态融合和提高分类性能方面的贡献。结论:通过交叉注意将基于图的光谱结构建模与深度视觉特征相结合,为高光谱病理诊断提供了一种强有力的方法。GICAF-Net在快速、准确、微创的术中分化FNH和HCC方面显示出强大的潜力,为肝肿瘤手术提供了宝贵的临床支持。
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引用次数: 0
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Computer methods and programs in biomedicine
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