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Quantifying the frequency modulation in electrograms during simulated atrial fibrillation in 2D domains. 在二维域中量化模拟心房颤动过程中的电图频率调制。
IF 7 2区 医学 Q1 BIOLOGY Pub Date : 2024-10-02 DOI: 10.1016/j.compbiomed.2024.109228
Juan P Ugarte, Alejandro Gómez-Echavarría, Catalina Tobón

Atrial fibrillation (AF) affects millions of people in the world, causing increased morbidity and mortality. Treatment involves antiarrhythmic drugs and catheter ablation, showing high success for paroxysmal AF but challenges for persistent AF. Experimental evidence suggests reentrant waves and rotors contribute to AF substrates. Ablation procedures rely on electroanatomical maps and electrogram (EGM) signals; however, current methods used in clinical practice lack consideration for time-frequency varying EGM components. The fractional Fourier transform (FrFT) can be adopted to capture time-varying frequency components, thereby enhancing the comprehension of arrhythmogenic substrates during AF for improved ablation strategies. To this end, a FrFT-based algorithm is developed to characterize non-stationary components in EGM signals from simulated AF episodes. The proposed algorithm comprises a pre-processing step to enhance the coarser features of the EGM waveform, a windowing process for dynamic assessment of the EGM, and a FrFT order optimization stage that seeks compact signal representations in fractional Fourier domains. The resulting order is related to the rate of frequency change in the signal, making it a useful indicator for frequency-modulated components. The FrFT-based algorithm is implemented on EGM signals from AF simulations in 2D domains representing a region of the atrial tissue. Consequently, the computed optimum FrFT orders are used to build maps that are spatially correlated to the underlying propagation dynamics of the simulated AF episode. The results evince that the extreme values in the optimum orders map pinpoint the localization of fibrillatory mechanisms, generating EGM activation waveforms with varying frequency content over time.

心房颤动(房颤)影响着全球数百万人,导致发病率和死亡率上升。治疗方法包括抗心律失常药物和导管消融术,对阵发性房颤的成功率很高,但对持续性房颤的成功率却很低。实验证据表明,再入波和转子是房颤的基质。消融程序依赖于电解剖图和电图(EGM)信号;然而,目前临床实践中使用的方法缺乏对时频变化的 EGM 成分的考虑。分数傅立叶变换(FrFT)可用于捕捉时变频率成分,从而增强对房颤期间致心律失常基质的理解,以改进消融策略。为此,我们开发了一种基于 FrFT 的算法,用于描述模拟房颤发作的 EGM 信号中的非稳态成分。所提出的算法包括一个用于增强 EGM 波形粗略特征的预处理步骤、一个用于动态评估 EGM 的开窗过程,以及一个在分数傅里叶域中寻求紧凑信号表示的 FrFT 阶次优化阶段。由此产生的阶次与信号中的频率变化率有关,是频率调制成分的有用指标。基于分数傅里叶的算法是在代表心房组织区域的二维域中对房颤模拟的 EGM 信号实施的。因此,计算出的最佳 FrFT 阶数被用于构建与模拟房颤发作的潜在传播动态在空间上相关的地图。结果表明,最佳阶次图中的极端值可精确定位纤颤机制,产生随时间变化频率内容的 EGM 激活波形。
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引用次数: 0
Multimodal brain tumor segmentation and classification from MRI scans based on optimized DeepLabV3+ and interpreted networks information fusion empowered with explainable AI. 基于可解释人工智能的优化 DeepLabV3+ 和解释网络信息融合的核磁共振成像扫描多模态脑肿瘤分割和分类。
IF 7 2区 医学 Q1 BIOLOGY Pub Date : 2024-10-01 DOI: 10.1016/j.compbiomed.2024.109183
Muhammad Sami Ullah, Muhammad Attique Khan, Hussain Mubarak Albarakati, Robertas Damaševičius, Shrooq Alsenan

Explainable artificial intelligence (XAI) aims to offer machine learning (ML) methods that enable people to comprehend, properly trust, and create more explainable models. In medical imaging, XAI has been adopted to interpret deep learning black box models to demonstrate the trustworthiness of machine decisions and predictions. In this work, we proposed a deep learning and explainable AI-based framework for segmenting and classifying brain tumors. The proposed framework consists of two parts. The first part, encoder-decoder-based DeepLabv3+ architecture, is implemented with Bayesian Optimization (BO) based hyperparameter initialization. The different scales are performed, and features are extracted through the Atrous Spatial Pyramid Pooling (ASPP) technique. The extracted features are passed to the output layer for tumor segmentation. In the second part of the proposed framework, two customized models have been proposed named Inverted Residual Bottleneck 96 layers (IRB-96) and Inverted Residual Bottleneck Self-Attention (IRB-Self). Both models are trained on the selected brain tumor datasets and extracted features from the global average pooling and self-attention layers. Features are fused using a serial approach, and classification is performed. The BO-based hyperparameters optimization of the neural network classifiers is performed and the classification results have been optimized. An XAI method named LIME is implemented to check the interpretability of the proposed models. The experimental process of the proposed framework was performed on the Figshare dataset, and an average segmentation accuracy of 92.68 % and classification accuracy of 95.42 % were obtained, respectively. Compared with state-of-the-art techniques, the proposed framework shows improved accuracy.

可解释人工智能(XAI)旨在提供机器学习(ML)方法,使人们能够理解、正确信任并创建更多可解释的模型。在医学影像领域,XAI 已被用于解释深度学习黑盒模型,以证明机器决策和预测的可信度。在这项工作中,我们提出了一个基于深度学习和可解释人工智能的框架,用于分割和分类脑肿瘤。该框架由两部分组成。第一部分是基于 DeepLabv3+ 架构的编码器-解码器,通过基于贝叶斯优化(BO)的超参数初始化来实现。通过 Atrous Spatial Pyramid Pooling(ASPP)技术提取不同尺度的特征。提取的特征被传递到输出层进行肿瘤分割。在拟议框架的第二部分,提出了两个定制模型,分别名为 "96 层倒置残余瓶颈(IRB-96)"和 "倒置残余瓶颈自注意(IRB-Self)"。这两个模型都是在选定的脑肿瘤数据集上进行训练,并从全局平均汇集层和自我注意层提取特征。使用串行方法融合特征并进行分类。对神经网络分类器进行了基于 BO 的超参数优化,并对分类结果进行了优化。此外,还采用了一种名为 LIME 的 XAI 方法来检查所提模型的可解释性。在 Figshare 数据集上对所提出的框架进行了实验,结果显示平均分割准确率为 92.68%,平均分类准确率为 95.42%。与最先进的技术相比,所提出的框架提高了准确率。
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引用次数: 0
Frontoparietal atrophy trajectories in cognitively unimpaired elderly individuals using longitudinal Bayesian clustering. 利用纵向贝叶斯聚类研究认知功能未受损的老年人的额顶叶萎缩轨迹。
IF 7 2区 医学 Q1 BIOLOGY Pub Date : 2024-10-01 DOI: 10.1016/j.compbiomed.2024.109190
G Lorenzon, K Poulakis, R Mohanty, M Kivipelto, M Eriksdotter, D Ferreira, E Westman

Introduction: Frontal and/or parietal atrophy has been reported during aging. To disentangle the heterogeneity previously observed, this study aimed to uncover different clusters of grey matter profiles and trajectories within cognitively unimpaired individuals.

Methods: Structural magnetic resonance imaging (MRI) data of 307 Aβ-negative cognitively unimpaired individuals were modelled between ages 60-85 from three cohorts worldwide. We applied unsupervised clustering using a novel longitudinal Bayesian approach and characterized the clusters' cerebrovascular and cognitive profiles.

Results: Four clusters were identified with different grey matter profiles and atrophy trajectories. Differences were mainly observed in frontal and parietal brain regions. These distinct frontoparietal grey matter profiles and longitudinal trajectories were differently associated with cerebrovascular burden and cognitive decline.

Discussion: Our findings suggest a conciliation of the frontal and parietal theories of aging, uncovering coexisting frontoparietal GM patterns. This could have important future implications for better stratification and identification of at-risk individuals.

简介额叶和/或顶叶在衰老过程中出现萎缩。为了揭示之前观察到的异质性,本研究旨在发现认知功能未受损个体的灰质特征和轨迹的不同集群:对全球三个队列中年龄在 60-85 岁之间的 307 名 Aβ 阴性认知功能未受损者的结构性磁共振成像(MRI)数据进行建模。我们采用一种新颖的纵向贝叶斯方法进行了无监督聚类,并描述了这些聚类的脑血管和认知特征:结果:我们发现了四个具有不同灰质特征和萎缩轨迹的集群。主要在额叶和顶叶脑区观察到差异。这些不同的额顶叶灰质特征和纵向轨迹与脑血管负担和认知能力下降有着不同的关联:讨论:我们的研究结果表明,额叶和顶叶衰老理论是一致的,发现了共存的额顶灰质模式。这对未来更好地分层和识别高危人群具有重要意义。
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引用次数: 0
Histopathology-driven prostate cancer identification: A VBIR approach with CLAHE and GLCM insights. 组织病理学驱动的前列腺癌识别:具有 CLAHE 和 GLCM 见解的 VBIR 方法。
IF 7 2区 医学 Q1 BIOLOGY Pub Date : 2024-10-01 DOI: 10.1016/j.compbiomed.2024.109213
Pramod K B Rangaiah, B P Pradeep Kumar, Robin Augustine

Efficient extraction and analysis of histopathological images are crucial for accurate medical diagnoses, particularly for prostate cancer. This research enhances histopathological image reclamation by integrating Visual-Based Image Reclamation (VBIR) techniques with contrast-limited adaptive Histogram Equalization (CLAHE) and the Gray-Level Co-occurrence Matrix (GLCM) algorithm. The proposed method leverages CLAHE to improve image contrast and visibility, crucial for regions with varying illumination, and employs a non-linear Support Vector Machine (SVM) to incorporate GLCM features. Our approach achieved a notable success rate of 89.6%, demonstrating significant improvement in image analysis. The average execution time for matched tissues was 41.23 s (standard deviation 36.87 s), and for unmatched tissues, 21.22 s (standard deviation 29.18 s). These results underscore the method's efficiency and reliability in processing histopathological images. The findings from this study highlight the potential of our method to enhance image reclamation processes, paving the way for further research and advancements in medical image analysis. The superior performance of our approach signifies its capability to significantly improve histopathological image analysis, contributing to more accurate and efficient diagnostic practices.

组织病理学图像的高效提取和分析对于准确的医疗诊断至关重要,尤其是前列腺癌。这项研究通过将基于视觉的图像重组(VBIR)技术与对比度限制自适应直方图均衡(CLAHE)和灰度共现矩阵(GLCM)算法相结合,增强了组织病理学图像重组的能力。所提出的方法利用 CLAHE 来提高图像对比度和可见度(这对光照变化的区域至关重要),并采用非线性支持向量机 (SVM) 来整合 GLCM 特征。我们的方法取得了 89.6% 的显著成功率,在图像分析方面取得了重大改进。匹配组织的平均执行时间为 41.23 秒(标准偏差为 36.87 秒),未匹配组织的平均执行时间为 21.22 秒(标准偏差为 29.18 秒)。这些结果凸显了该方法在处理组织病理学图像时的效率和可靠性。这项研究的结果凸显了我们的方法在增强图像再生过程中的潜力,为医学图像分析的进一步研究和进步铺平了道路。我们的方法性能优越,表明它有能力显著改善组织病理学图像分析,为更准确、更高效的诊断实践做出贡献。
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引用次数: 0
Non-invasive regional parameter identification of degenerated human meniscus. 变性人体半月板的无创区域参数识别。
IF 7 2区 医学 Q1 BIOLOGY Pub Date : 2024-10-01 DOI: 10.1016/j.compbiomed.2024.109230
Jonas Schwer, Fabio Galbusera, Anita Ignatius, Lutz Dürselen, Andreas Martin Seitz

Accurate identification of local changes in the biomechanical properties of the normal and degenerative meniscus is critical to better understand knee joint osteoarthritis onset and progression. Ex-vivo material characterization is typically performed on specimens obtained from different locations, compromising the tissue's structural integrity and thus altering its mechanical behavior. Therefore, the aim of this in-silico study was to establish a non-invasive method to determine the region-specific material properties of the degenerated human meniscus. In a previous experimental magnetic resonance imaging (MRI) study, the spatial displacement of the meniscus and its root attachments in mildly degenerated (n = 12) and severely degenerated (n = 12) cadaveric knee joints was determined under controlled subject-specific axial joint loading. To simulate the experimental response of the lateral and medial menisci, individual finite element models were created utilizing a transverse isotropic hyper-poroelastic constitutive material formulation. The superficial displacements were applied to the individual models to calculate the femoral reaction force in an inverse finite element analysis. During particle swarm optimization, the four most sensitive material parameters were varied to minimize the error between the femoral reaction force and the force applied in the MRI loading experiment. Individual global and regional parameter sets were identified. In addition to in-depth model verification, prediction errors were determined to quantify the reliability of the identified parameter sets. Both compressibility of the solid meniscus matrix (+141 %, p ≤ 0.04) and hydraulic permeability (+53 %, p ≤ 0.04) were significantly increased in the menisci of severely degenerated knees compared to mildly degenerated knees, irrespective of the meniscus region. By contrast, tensile and shear properties were unaffected by progressive knee joint degeneration. Overall, the optimization procedure resulted in reliable and robust parameter sets, as evidenced by mean prediction errors of <1 %. In conclusion, the proposed approach demonstrated high potential for application in clinical practice, where it might provide a non-invasive diagnostic tool for the early detection of osteoarthritic changes within the knee joint.

准确识别正常和退行性半月板生物力学特性的局部变化,对于更好地了解膝关节骨关节炎的发病和发展至关重要。体外材料表征通常是在从不同位置获取的标本上进行的,这会损害组织结构的完整性,从而改变其机械行为。因此,这项体内研究的目的是建立一种非侵入性方法,以确定退化人体半月板的特定区域材料特性。在之前的一项磁共振成像(MRI)实验研究中,在受控的特定受试者轴向关节加载下,测定了轻度退化(n = 12)和严重退化(n = 12)尸体膝关节中半月板及其根部附件的空间位移。为了模拟外侧和内侧半月板的实验响应,利用横向各向同性超多孔弹性材料构成公式创建了单个有限元模型。在反向有限元分析中,将表面位移应用于单个模型,以计算股骨反作用力。在粒子群优化过程中,改变了四个最敏感的材料参数,以尽量减小股骨反作用力与核磁共振加载实验中的作用力之间的误差。最终确定了单独的全局和区域参数集。除了对模型进行深入验证外,还确定了预测误差,以量化已确定参数集的可靠性。与轻度退化的膝关节相比,无论半月板区域如何,严重退化膝关节的半月板固体基质的可压缩性(+141%,p≤0.04)和液压渗透性(+53%,p≤0.04)都显著增加。相比之下,拉伸和剪切特性不受膝关节逐渐退化的影响。总体而言,优化程序产生了可靠和稳健的参数集,其平均预测误差为
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引用次数: 0
Enhancing ensemble classifiers utilizing gaze tracking data for autism spectrum disorder diagnosis 利用凝视跟踪数据增强自闭症谱系障碍诊断的集合分类器
IF 7 2区 医学 Q1 BIOLOGY Pub Date : 2024-09-30 DOI: 10.1016/j.compbiomed.2024.109184

Problem:

Diagnosing Autism Spectrum Disorder (ASD) remains a significant challenge, especially in regions where access to specialists is limited. Computer-based approaches offer a promising solution to make diagnosis more accessible. Eye tracking has emerged as a valuable technique in aiding the diagnosis of ASD. Typically, individuals’ gaze patterns are monitored while they view videos designed according to established paradigms. In a previous study, we developed a method to classify individuals as having ASD or Typical Development (TD) by processing eye-tracking data using Random Forest ensembles, with a focus on a paradigm known as joint attention.

Aim:

This article aims to enhance our previous work by evaluating alternative algorithms and ensemble strategies, with a particular emphasis on the role of anticipation features in diagnosis.

Methods:

Utilizing stimuli based on joint attention and the concept of “floating regions of interest” from our earlier research, we identified features that indicate gaze anticipation or delay. We then tested seven class balancing strategies, applied seven dimensionality reduction algorithms, and combined them with five different classifier induction algorithms. Finally, we employed the stacking technique to construct an ensemble model.

Results:

Our findings showed a significant improvement, achieving an F1-score of 95.5%, compared to the 82% F1-score from our previous work, through the use of a heterogeneous stacking meta-classifier composed of diverse induction algorithms.

Conclusion:

While there remains an opportunity to explore new algorithms and features, the approach proposed in this article has the potential to be applied in clinical practice, contributing to increased accessibility to ASD diagnosis.
社会问题:自闭症谱系障碍(ASD)的诊断仍然是一项巨大的挑战,尤其是在专家资源有限的地区。基于计算机的方法提供了一种有前途的解决方案,使诊断更容易获得。眼动追踪已成为辅助诊断 ASD 的一项重要技术。通常情况下,患者在观看根据既定范式设计的视频时,其注视模式会受到监控。在之前的一项研究中,我们开发了一种方法,通过使用随机森林组合处理眼球跟踪数据,将个体划分为 ASD 或典型发育(TD)患者,重点关注被称为联合注意的范式。方法:我们利用基于联合注意的刺激和之前研究中的 "浮动感兴趣区 "概念,确定了表明注视预期或延迟的特征。然后,我们测试了七种类平衡策略,应用了七种降维算法,并将它们与五种不同的分类器归纳算法相结合。结果:我们的研究结果表明,通过使用由不同归纳算法组成的异构堆叠元分类器,我们的F1得分达到了95.5%,与我们之前工作中82%的F1得分相比有了显著的提高。
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引用次数: 0
Patient-based multilevel transcriptome exploration highlights relevant chemokines and chemokine receptor axes in glioblastoma. 基于患者的多层次转录组探索凸显了胶质母细胞瘤中的相关趋化因子和趋化因子受体轴。
IF 7 2区 医学 Q1 BIOLOGY Pub Date : 2024-09-30 DOI: 10.1016/j.compbiomed.2024.109197
Giulia D'Uonnolo, Damla Isci, Bakhtiyor Nosirov, Amandine Kuppens, May Wantz, Petr V Nazarov, Anna Golebiewska, Bernard Rogister, Andy Chevigné, Virginie Neirinckx, Martyna Szpakowska

Chemokines and their receptors form a complex interaction network, crucial for precise leukocyte positioning and trafficking. In cancer, they promote malignant cell proliferation and survival but are also critical for immune cell infiltration in the tumor microenvironment. Glioblastoma (GBM) is the most common and lethal brain tumor, characterized by an immunosuppressive TME, with restricted immune cell infiltration. A better understanding of chemokine-receptor interactions is therefore essential for improving tumor immunogenicity. In this study, we assessed the expression of all human chemokines in adult-type diffuse gliomas, with particular focus on GBM, based on patient-derived samples. Publicly available bulk RNA sequencing datasets allowed us to identify the chemokines most abundantly expressed in GBM, with regard to disease severity and across different tumor subregions. To gain insight into the chemokines-receptor network at the single cell resolution, we explored GBmap, a curated resource integrating multiple scRNAseq datasets from different published studies. Our study constitutes the first patient-based handbook highlighting the relevant chemokine-receptor crosstalks, which are of significant interest in the perspective of a therapeutic modulation of the TME in GBM.

趋化因子及其受体形成了一个复杂的相互作用网络,对白细胞的精确定位和迁移至关重要。在癌症中,它们促进恶性细胞的增殖和存活,同时也是肿瘤微环境中免疫细胞浸润的关键。胶质母细胞瘤(GBM)是最常见、最致命的脑肿瘤,其特点是具有免疫抑制作用的TME,免疫细胞浸润受限。因此,更好地了解趋化因子与受体之间的相互作用对于改善肿瘤的免疫原性至关重要。在这项研究中,我们根据患者样本评估了所有人类趋化因子在成人型弥漫性胶质瘤中的表达情况,尤其关注GBM。通过公开的大容量 RNA 测序数据集,我们确定了在 GBM 中表达最丰富的趋化因子,这些趋化因子与疾病的严重程度和不同的肿瘤亚区域有关。为了深入了解单细胞分辨率的趋化因子-受体网络,我们探索了 GBmap,这是一个整合了来自不同已发表研究的多个 scRNAseq 数据集的资源库。我们的研究构成了第一本以患者为基础的手册,其中强调了相关的趋化因子-受体串联,这对治疗调控 GBM 的 TME 具有重要意义。
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引用次数: 0
Visual interpretation of deep learning model in ECG classification: A comprehensive evaluation of feature attribution methods 深度学习模型在心电图分类中的可视化解读:特征归因方法的综合评估
IF 7 2区 医学 Q1 BIOLOGY Pub Date : 2024-09-30 DOI: 10.1016/j.compbiomed.2024.109088
Feature attribution methods can visually highlight specific input regions containing influential aspects affecting a deep learning model's prediction. Recently, the use of feature attribution methods in electrocardiogram (ECG) classification has been sharply increasing, as they assist clinicians in understanding the model's decision-making process and assessing the model's reliability. However, a careful study to identify suitable methods for ECG datasets has been lacking, leading researchers to select methods without a thorough understanding of their appropriateness. In this work, we conduct a large-scale assessment by considering eleven popular feature attribution methods across five large ECG datasets using a model based on the ResNet-18 architecture. Our experiments include both automatic evaluations and human evaluations. Annotated datasets were utilized for automatic evaluations and three cardiac experts were involved for human evaluations. We found that Guided Grad-CAM, particularly when its absolute values are utilized, achieves the best performance. When Guided Grad-CAM was utilized as the feature attribution method, cardiac experts confirmed that it can identify diagnostically relevant electrophysiological characteristics, although its effectiveness varied across the 17 different diagnoses that we have investigated.
特征归因方法可以直观地突出特定的输入区域,这些区域包含影响深度学习模型预测的有影响力的方面。最近,特征归因方法在心电图(ECG)分类中的使用急剧增加,因为它们有助于临床医生理解模型的决策过程并评估模型的可靠性。然而,一直以来都缺乏针对心电图数据集确定合适方法的细致研究,导致研究人员在选择方法时没有充分了解这些方法是否合适。在这项工作中,我们使用基于 ResNet-18 架构的模型,对五个大型心电图数据集中的十一种流行特征归因方法进行了大规模评估。我们的实验包括自动评估和人工评估。注释数据集用于自动评估,三位心脏病专家参与了人工评估。我们发现,Guided Grad-CAM(尤其是在使用其绝对值时)取得了最佳性能。当使用 "引导梯度-CAM "作为特征归因方法时,心脏病专家证实它能识别与诊断相关的电生理特征,尽管其有效性在我们研究的 17 种不同诊断中各不相同。
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引用次数: 0
Identification, isoform classification, ligand binding, and database construction of the protein-tyrosine sulfotransferase family in metazoans 元古动物中蛋白-酪氨酸磺基转移酶家族的鉴定、同工酶分类、配体结合和数据库构建。
IF 7 2区 医学 Q1 BIOLOGY Pub Date : 2024-09-29 DOI: 10.1016/j.compbiomed.2024.109208
Protein tyrosine sulfonation (PTS) influences various crucial physiological and pathological processes in animals. Protein-tyrosine sulfotransferase (TPST) serves as a pivotal enzyme in this process. Research on TPST is still in its early stages, and current identification methods have not yet effectively differentiated TPST from other type II sulfotransferases. Furthermore, this study has revealed that TPST in animals is highly conserved and exhibits significant differences when compared to other sulfotransferases and TPSTs in non-animal species. However, precise and efficient methods for identifying TPST, conducting subfamily classification, performing functional and sequence analyses, and accessing corresponding databases and analytical platforms for the entire TPST family of metazoan species are lacking. These findings provide a foundation for more in-depth research on TPST in animals and are crucial for advancing the understanding of PTS and its broader impacts.
In this study, a Hidden Markov Model (TPST-HMM) was formulated based on the conserved motifs binding to the substrate PAPS and the ligand tyrosine in metazoan TPSTs. TPST-HMM successfully identified more than 91.8 % of metazoan TPSTs in UniProt (e-value < 1e-5). When the threshold was adjusted to 1e-20, the identification rate of TPST was 83.9 % in metazoans and approximately 0 % in other species (fungi, bacteria, etc.). Subsequently, 5638 TPSTs were identified from 1311 metazoan genomes, and these TPSTs were classified into three subfamilies. The classification of the TPST1 and TPST2 subtypes, which were initially annotated in mammals, was extended across vertebrates. Additionally, a novel subtype, TPST3, belonging to a distinct subfamily, was discovered in invertebrates. We proposed a molecular docking prediction method for TPST and tyrosine ligands based on the observation that TPST-tyrosine binding recognition and binding in metazoans were primarily driven by electrostatic interactions.
Finally, a database website for animal TPST sequences was established (http://sz.bjfskj.com/). The website included an online tool for identifying TPST protein sequences, enabling annotation and visualization of functional motifs and active amino acids. Its design aimed to assist users in studying TPST in animals.
蛋白质酪氨酸磺化(PTS)影响动物的各种关键生理和病理过程。蛋白-酪氨酸磺基转移酶(TPST)是这一过程中的关键酶。对 TPST 的研究仍处于早期阶段,目前的鉴定方法还不能有效地区分 TPST 和其他 II 型磺基转移酶。此外,本研究还发现,动物体内的 TPST 具有高度保守性,与其他磺基转移酶和非动物物种中的 TPST 相比具有显著差异。然而,目前还缺乏精确有效的方法来鉴定 TPST、进行亚家族分类、进行功能和序列分析,以及访问元动物整个 TPST 家族的相应数据库和分析平台。这些发现为更深入地研究动物中的 TPST 提供了基础,对于促进对 PTS 及其广泛影响的了解至关重要。在本研究中,根据元古动物 TPST 与底物 PAPS 和配体酪氨酸结合的保守基团,建立了隐马尔可夫模型(TPST-HMM)。TPST-HMM 成功鉴定了 UniProt 中 91.8% 以上的元古宙 TPSTs(e 值小于 1e-5)。当阈值调整为 1e-20 时,元古类 TPST 的鉴定率为 83.9%,其他物种(真菌、细菌等)的鉴定率约为 0%。随后,从 1311 个元动物基因组中鉴定出 5638 个 TPSTs,并将这些 TPSTs 分成三个亚家族。TPST1 和 TPST2 亚型最初在哺乳动物中得到注释,其分类已扩展到脊椎动物。此外,我们还在无脊椎动物中发现了一个属于不同亚家族的新亚型 TPST3。我们提出了一种 TPST 和酪氨酸配体的分子对接预测方法,其依据是观察到 TPST 与酪氨酸的结合识别和结合在元古脊椎动物中主要由静电相互作用驱动。最后,建立了动物 TPST 序列数据库网站(http://sz.bjfskj.com/)。该网站包括一个用于识别 TPST 蛋白序列的在线工具,可对功能基团和活性氨基酸进行注释和可视化。该网站的设计旨在帮助用户研究动物中的 TPST。
{"title":"Identification, isoform classification, ligand binding, and database construction of the protein-tyrosine sulfotransferase family in metazoans","authors":"","doi":"10.1016/j.compbiomed.2024.109208","DOIUrl":"10.1016/j.compbiomed.2024.109208","url":null,"abstract":"<div><div>Protein tyrosine sulfonation (PTS) influences various crucial physiological and pathological processes in animals. Protein-tyrosine sulfotransferase (TPST) serves as a pivotal enzyme in this process. Research on TPST is still in its early stages, and current identification methods have not yet effectively differentiated TPST from other type II sulfotransferases. Furthermore, this study has revealed that TPST in animals is highly conserved and exhibits significant differences when compared to other sulfotransferases and TPSTs in non-animal species. However, precise and efficient methods for identifying TPST, conducting subfamily classification, performing functional and sequence analyses, and accessing corresponding databases and analytical platforms for the entire TPST family of metazoan species are lacking. These findings provide a foundation for more in-depth research on TPST in animals and are crucial for advancing the understanding of PTS and its broader impacts.</div><div>In this study, a Hidden Markov Model (TPST-HMM) was formulated based on the conserved motifs binding to the substrate PAPS and the ligand tyrosine in metazoan TPSTs. TPST-HMM successfully identified more than 91.8 % of metazoan TPSTs in UniProt (e-value &lt; 1e-5). When the threshold was adjusted to 1e-20, the identification rate of TPST was 83.9 % in metazoans and approximately 0 % in other species (fungi, bacteria, etc.). Subsequently, 5638 TPSTs were identified from 1311 metazoan genomes, and these TPSTs were classified into three subfamilies. The classification of the TPST1 and TPST2 subtypes, which were initially annotated in mammals, was extended across vertebrates. Additionally, a novel subtype, TPST3, belonging to a distinct subfamily, was discovered in invertebrates. We proposed a molecular docking prediction method for TPST and tyrosine ligands based on the observation that TPST-tyrosine binding recognition and binding in metazoans were primarily driven by electrostatic interactions.</div><div>Finally, a database website for animal TPST sequences was established (<span><span>http://sz.bjfskj.com/</span><svg><path></path></svg></span>). The website included an online tool for identifying TPST protein sequences, enabling annotation and visualization of functional motifs and active amino acids. Its design aimed to assist users in studying TPST in animals.</div></div>","PeriodicalId":10578,"journal":{"name":"Computers in biology and medicine","volume":null,"pages":null},"PeriodicalIF":7.0,"publicationDate":"2024-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343049","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
Integrated analysis of circRNA regulation with ADARB2 enrichment in inhibitory neurons 抑制性神经元中富含 ADARB2 的 circRNA 调控综合分析
IF 7 2区 医学 Q1 BIOLOGY Pub Date : 2024-09-28 DOI: 10.1016/j.compbiomed.2024.109212
This study investigates the regulation of circular RNAs (circRNAs) with Adenosine Deaminase RNA Specific B2 (ADARB2) enrichment specifically in inhibitory neurons. Using an integrated analysis combining high-throughput sequencing and bioinformatics approaches, we identified a group of circRNAs that are potentially enhanced by ADARB2. Our findings highlight the pivotal role of ADARB2 in circRNA synthesis within inhibitory neurons, likely through its specific binding to precursor RNAs, which facilitates circRNA biogenesis.
本研究探讨了抑制性神经元中富含腺苷脱氨酶RNA特异性B2(ADARB2)的环状RNA(circRNA)的调控。通过结合高通量测序和生物信息学方法的综合分析,我们发现了一组可能被ADARB2增强的环状RNA。我们的发现突显了ADARB2在抑制性神经元内circRNA合成过程中的关键作用,它可能通过与前体RNA的特异性结合促进了circRNA的生物生成。
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引用次数: 0
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Computers in biology and medicine
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