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Optical detection of the spatial structural alteration in the human brain tissues/cells and DNA/chromatin due to Parkinson's disease. 帕金森病引起的人脑组织/细胞和DNA/染色质空间结构改变的光学检测
Pub Date : 2024-12-25
Fatemah Alharthi, Dhruvil Solanki, Ishmael Apachigawo, Jianfeng Xiao, Mohammad Moshahid Khan, Prabhakar Pradhan

Parkinson's disease (PD) is considered one of the most frequent neurological diseases in the world. There is a need to study the early and efficient biomarkers of Parkinson's, such as changes in structural disorders like DNA/chromatin, especially at the subcellular level in the human brain. We used two techniques, Partial wave spectroscopy (PWS) and Inverse Participation Ratio (IPR), to detect the changes in structural disorder in the human brain tissue samples. It was observed from the PWS experiment that there was an increase in structural disorder in Parkinson's disease tissues/cells when compared to normal tissues/cells using mesoscopic light transport theory. Furthermore, the IPR experiment also showed DNA/chromatin structural alterations that have the same trend and support the PWS results. The increase in mass density in the nuclei components, such as DNA/chromatin, can be linked to the aggregation of alpha-synuclein in the substantia nigra of the brain. This protein deposition is considered a significant cause of neuronal death in the brains of PD patients. We also did a histological analysis of brain tissues, which supports our results from dual photonics techniques. The results show that this dual technique is a powerful approach to detect the changes. Our results highlight the potential of the parameter, related to the structural disorder strength, as an efficient biomarker for PD progress, paving the way for research into early disease detection.

帕金森病被认为是世界上最常见的神经系统疾病之一。有必要研究帕金森病的早期和有效的生物标志物,例如DNA/染色质等结构紊乱的变化,特别是在人脑的亚细胞水平上。采用分波光谱(PWS)和逆参与比(IPR)两种技术检测人脑组织样本中结构紊乱的变化。从PWS实验中观察到,使用介观光输运理论,与正常组织/细胞相比,帕金森病组织/细胞的结构紊乱有所增加。此外,IPR实验还显示DNA/染色质结构改变具有相同的趋势,并支持PWS结果。细胞核成分(如DNA/染色质)质量密度的增加可能与大脑黑质中α -突触核蛋白的聚集有关。这种蛋白质沉积被认为是PD患者大脑神经元死亡的重要原因。我们还对脑组织进行了组织学分析,这支持了双光子技术的结果。结果表明,这种双重技术是一种有效的检测变化的方法。我们的研究结果强调了与结构紊乱强度相关的参数作为PD进展的有效生物标志物的潜力,为早期疾病检测的研究铺平了道路。
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引用次数: 0
An AI-directed analytical study on the optical transmission microscopic images of Pseudomonas aeruginosa in planktonic and biofilm states. 浮游和生物膜状态铜绿假单胞菌光学透射显微图像的人工智能定向分析研究。
Pub Date : 2024-12-24
Bidisha Sengupta, Mousa Alrubayan, Yibin Wang, Esther Mallet, Angel Torres, Ravyn Solis, Haifeng Wang, Prabhakar Pradhan

Biofilms are resistant microbial cell aggregates that pose risks to health and food industries and produce environmental contamination. Accurate and efficient detection and prevention of biofilms are challenging and demand interdisciplinary approaches. This multidisciplinary research reports the application of a deep learning-based artificial intelligence (AI) model for detecting biofilms produced by Pseudomonas aeruginosa with high accuracy. Aptamer DNA templated silver nanocluster (Ag-NC) was used to prevent biofilm formation, which produced images of the planktonic states of the bacteria. Large-volume bright field images of bacterial biofilms were used to design the AI model. In particular, we used U-Net with ResNet encoder enhancement to segment biofilm images for AI analysis. Different degrees of biofilm structures can be efficiently detected using ResNet18 and ResNet34 backbones. The potential applications of this technique are also discussed.

生物膜是对健康和食品工业构成风险并造成环境污染的耐药微生物细胞聚集体。准确和有效的检测和预防生物膜是具有挑战性的,需要跨学科的方法。这项多学科研究报告了一种基于深度学习的人工智能(AI)模型的应用,用于高精度检测铜绿假单胞菌产生的生物膜。核酸适配体DNA模板银纳米簇(Ag-NC)用于防止生物膜的形成,从而产生细菌浮游状态的图像。利用细菌生物膜的大体积亮场图像设计人工智能模型。特别是,我们使用带有ResNet编码器增强的U-Net来分割生物膜图像以进行人工智能分析。使用ResNet18和ResNet34骨干网可以有效地检测不同程度的生物膜结构。并对该技术的潜在应用进行了讨论。
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引用次数: 0
Agreement of Image Quality Metrics with Radiological Evaluation in the Presence of Motion Artifacts. 运动伪影存在下图像质量度量与放射学评价的一致性。
Pub Date : 2024-12-24
Elisa Marchetto, Hannah Eichhorn, Daniel Gallichan, Julia A Schnabel, Melanie Ganz

Purpose: Reliable image quality assessment is crucial for evaluating new motion correction methods for magnetic resonance imaging. In this work, we compare the performance of commonly used reference-based and reference-free image quality metrics on a unique dataset with real motion artifacts. We further analyze the image quality metrics' robustness to typical pre-processing techniques.

Methods: We compared five reference-based and five reference-free image quality metrics on data acquired with and without intentional motion (2D and 3D sequences). The metrics were recalculated seven times with varying pre-processing steps. The anonymized images were rated by radiologists and radiographers on a 1-5 Likert scale. Spearman correlation coefficients were computed to assess the relationship between image quality metrics and observer scores.

Results: All reference-based image quality metrics showed strong correlation with observer assessments, with minor performance variations across sequences. Among reference-free metrics, Average Edge Strength offers the most promising results, as it consistently displayed stronger correlations across all sequences compared to the other reference-free metrics. Overall, the strongest correlation was achieved with percentile normalization and restricting the metric values to the skull-stripped brain region. In contrast, correlations were weaker when not applying any brain mask and using min-max or no normalization.

Conclusion: Reference-based metrics reliably correlate with radiological evaluation across different sequences and datasets. Pre-processing steps, particularly normalization and brain masking, significantly influence the correlation values. Future research should focus on refining pre-processing techniques and exploring machine learning approaches for automated image quality evaluation.

目的:可靠的图像质量评估是评估磁共振成像运动校正新方法的关键。在这项工作中,我们比较了常用的基于参考和无参考的图像质量指标在具有真实运动伪影的独特数据集上的性能。我们进一步分析了图像质量指标对典型预处理技术的鲁棒性。方法:我们比较了五种基于参考和五种无参考的图像质量指标在有和没有故意运动(2D和3D序列)的情况下获得的数据。使用不同的预处理步骤重新计算指标七次。放射科医生和放射技师按照1-5的李克特量表对这些匿名图像进行评分。计算Spearman相关系数来评估图像质量指标与观察者评分之间的关系。结果:所有基于参考的图像质量指标显示与观察者评估有很强的相关性,在序列之间有较小的性能变化。在无参考指标中,平均边缘强度提供了最有希望的结果,因为与其他无参考指标相比,它始终显示出所有序列之间更强的相关性。总体而言,最强的相关性是通过百分位数归一化实现的,并将度量值限制在去颅骨的大脑区域。相比之下,当不使用任何脑罩和使用最小最大值或不进行归一化时,相关性较弱。结论:基于参考的指标与不同序列和数据集的放射学评估可靠相关。预处理步骤,特别是归一化和脑掩蔽,显著影响相关值。未来的研究应该集中在改进预处理技术和探索自动图像质量评估的机器学习方法上。
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引用次数: 0
Optimizing In Vivo Data Acquisition for Robust Clinical Microvascular Imaging Using Ultrasound Localization Microscopy. 利用超声定位显微镜优化临床微血管成像的体内数据采集。
Pub Date : 2024-12-24
Chengwu Huang, U-Wai Lok, Jingke Zhang, Xiang Yang Zhu, James D Krier, Amy Stern, Kate M Knoll, Kendra E Petersen, Kathryn A Robinson, Gina K Hesley, Andrew J Bentall, Thomas D Atwell, Andrew D Rule, Lilach O Lerman, Shigao Chen

Ultrasound localization microscopy (ULM) enables microvascular imaging at spatial resolutions beyond the acoustic diffraction limit, offering significant clinical potentials. However, ULM performance relies heavily on microbubble (MB) signal sparsity, the number of detected MBs, and signal-to-noise ratio (SNR), all of which vary in clinical scenarios involving bolus MB injections. These sources of variations underscore the need to optimize MB dosage, data acquisition timing, and imaging settings in order to standardize and optimize ULM of microvasculature. This pilot study investigated temporal changes in MB signals during bolus injections in both pig and human models to optimize data acquisition for clinical ULM. Quantitative indices were developed to evaluate MB signal quality, guiding selection of acquisition timing that balances the MB localization quality and adequate MB counts. The effects of transmitted voltage and dosage were also explored. In the pig model, a relatively short window (approximately 10 seconds) for optimal acquisition was identified during the rapid wash-out phase, highlighting the need for real-time MB signal monitoring during data acquisition. The slower wash-out phase in humans allowed for a more flexible imaging window of 1-2 minutes, while trade-offs were observed between localization quality and MB density (or acquisition length) at different wash-out phase timings. Guided by these findings, robust ULM imaging was achieved in both pig and human kidneys using a short period of data acquisition, demonstrating its feasibility in clinical practice. This study provides insights into optimizing data acquisition for consistent and reproducible ULM, paving the way for its standardization and broader clinical applications.

超声定位显微镜(ULM)使微血管成像的空间分辨率超过声衍射极限,具有重要的临床潜力。然而,ULM的性能在很大程度上依赖于微泡(MB)信号的稀疏度、检测到的MB的数量和信噪比(SNR),所有这些在临床情况下都是不同的。这些变化的来源强调了优化MB剂量、数据采集时间和成像设置的必要性,以便标准化和优化微血管ULM。为了优化临床ULM的数据采集,本初步研究在猪和人类模型中研究了大剂量注射期间MB信号的时间变化。开发了量化指标来评估MB信号质量,指导选择采集时间,以平衡MB定位质量和足够的MB计数。并探讨了传输电压和剂量的影响。在猪模型中,在快速冲洗阶段确定了相对较短的最佳采集窗口(约10秒),这突出了在数据采集过程中对实时MB信号监测的需求。人类较慢的冲洗阶段允许1-2分钟的更灵活的成像窗口,同时在不同的冲洗阶段时间观察到定位质量和MB密度(或采集长度)之间的权衡。在这些发现的指导下,利用短时间的数据采集,在猪和人的肾脏中实现了强大的ULM成像,证明了其在临床实践中的可行性。该研究为优化一致性和可重复性ULM的数据采集提供了见解,为其标准化和更广泛的临床应用铺平了道路。
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引用次数: 0
Comprehensive Optimization of Interferometric Diffusing Wave Spectroscopy (iDWS). 干涉散射波光谱(iDWS)的综合优化。
Pub Date : 2024-12-23
Mingjun Zhao, Leah Dickstein, Akshay S Nadig, Wenjun Zhou, Santosh Aparanji, Hector Garcia Estrada, Shing-Jiuan Liu, Ting Zhou, Weijian Yang, Aaron Lord, Vivek J Srinivasan

It has been shown that light speckle fluctuations provide a means for noninvasive measurements of cerebral blood flow index (CBFi). While conventional Diffuse Correlation Spectroscopy (DCS) provides marginal brain sensitivity for CBFi in adult humans, new techniques have recently emerged to improve diffuse light throughput and thus, brain sensitivity. Here we further optimize one such approach, interferometric diffusing wave spectroscopy (iDWS), with respect to number of independent channels, camera duty cycle and full well capacity, incident power, noise and artifact mitigation, and data processing. We build the system on a cart and define conditions for stable operation. We show pulsatile CBFi monitoring at 4-4.5 cm source-collector separation in adults with moderate pigmentation (Fitzpatrick 4). We also report preliminary clinical measurements in the Neuro Intensive Care Unit (Neuro ICU). These results push the boundaries of iDWS CBFi monitoring performance beyond previous reports.

研究表明,光斑波动为无创测量脑血流指数(CBFi)提供了一种方法。虽然传统的漫射相关光谱(DCS)只能提供成年人CBFi的边缘脑灵敏度,但最近出现的新技术可以提高漫射光吞吐量,从而提高脑灵敏度。在这里,我们进一步优化了一种这样的方法,即干涉漫射波光谱(iDWS),涉及独立通道数量、相机占空比和全井容量、入射功率、噪声和人为干扰缓解以及数据处理。我们将系统建立在手推车上,并定义了稳定运行的条件。我们在中度色素沉着的成人中显示了4-4.5 cm源收集器分离处的脉搏性CBFi监测(Fitzpatrick 4)。我们还报告了神经重症监护室(Neuro ICU)的初步临床测量结果。这些结果突破了iDWS CBFi监测性能的界限,超越了以前的报告。
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引用次数: 0
Diverging network architecture of the C. elegans connectome and signaling network. 秀丽隐杆线虫连接体和信号网络的分化网络结构。
Pub Date : 2024-12-19
Sophie Dvali, Caio Seguin, Richard Betzel, Andrew M Leifer

The connectome describes the complete set of synaptic contacts through which neurons communicate. While the architecture of the C. elegans connectome has been extensively characterized, much less is known about the organization of causal signaling networks arising from functional interactions between neurons. Understanding how effective communication pathways relate to or diverge from the underlying structure is a central question in neuroscience. Here, we analyze the modular architecture of the C. elegans signal propagation network, measured via calcium imaging and optogenetics, and compare it to the underlying anatomical wiring measured by electron microscopy. Compared to the connectome, we find that signaling modules are not aligned with the modular boundaries of the anatomical network, highlighting an instance where function deviates from structure. An exception to this is the pharynx which is delineated into a separate community in both anatomy and signaling. We analyze the cellular compositions of the signaling architecture and find that its modules are enriched for specific cell types and functions, suggesting that the network modules are neurobiologically relevant. Lastly, we identify a "rich club" of hub neurons in the signaling network. The membership of the signaling rich club differs from the rich club detected in the anatomical network, challenging the view that structural hubs occupy positions of influence in functional (signaling) networks. Our results provide new insight into the interplay between brain structure, in the form of a complete synaptic-level connectome, and brain function, in the form of a system-wide causal signal propagation atlas.

连接组描述了一整套突触接触,神经元通过这些接触进行交流。虽然秀丽隐杆线虫连接组的结构已经被广泛表征,但对神经元之间的功能相互作用产生的因果信号网络的组织知之甚少。了解有效的沟通途径如何与潜在的结构相关联或偏离是神经科学的一个核心问题。在这里,我们分析了秀丽隐杆线虫信号传播网络的模块化结构,通过钙成像和光遗传学测量,并将其与电子显微镜测量的潜在解剖线路进行比较。与连接体相比,我们发现信号模块与解剖网络的模块边界不一致,突出了功能偏离结构的实例。咽是一个例外,它在解剖和信号方面都被划分为一个单独的群落。我们分析了信号结构的细胞组成,发现其模块丰富于特定的细胞类型和功能,这表明网络模块与神经生物学相关。最后,我们确定了信号网络中中枢神经元的“富俱乐部”。信号丰富俱乐部的成员不同于解剖网络中检测到的丰富俱乐部,这挑战了结构枢纽在功能(信号)网络中占据影响地位的观点。我们的研究结果为大脑结构之间的相互作用提供了新的见解,以一个完整的突触级连接组的形式,和大脑功能,以一个全系统的因果信号传播图谱的形式。
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引用次数: 0
Joint estimation of activity, attenuation and motion in respiratory-self-gated time-of-flight PET. 呼吸自门控飞行时间PET活性、衰减和运动的联合估计。
Pub Date : 2024-12-19
Masoud Elhamiasl, Frederic Jolivet, Ahmadreza Rezaei, Michael Fieseler, Klaus Schäfers, Johan Nuyts, Georg Schramm, Fernando Boada

Motivation: Whole-body Positron Emission Tomography (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 time-of-flight (TOF) PET. These methods enable the reconstruction of a single activity image free from motion and attenuation artifacts.

Methods: The proposed methods were evaluated using data from the anthropomorphic Wilhelm phantom acquired on a Siemens mCT PET/CT system, as well as three clinical [18F]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.

Results: 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 (using our 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.

Conclusion: 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.

动机:全身正电子发射断层扫描(PET)成像在采集过程中经常受到呼吸运动的阻碍,导致重建活动图像的质量显著下降。PET/CT成像的另一个挑战来自于基于CT的衰减校正和PET采集之间的呼吸相位不匹配,从而导致衰减伪影。为了解决这些问题,我们提出了两种新的、纯数据驱动的方法来联合估计呼吸自门控飞行时间(TOF) PET的活动、衰减和运动。这些方法使单个活动图像的重建不受运动和衰减伪影的影响。方法:使用西门子mCT PET/CT系统获得的拟人化威廉幻影数据,以及GE DMI PET/CT系统获得的三个临床[18F]FDG PET/CT数据集,对所提出的方法进行评估。视觉评估图像质量以识别运动和衰减伪影。在没有运动建模的重建、有运动建模但“静态”衰减校正的重建以及我们提出的方法中,定量比较了病灶摄取值。结果:对于Wilhelm幻影,所提出的方法提供的图像质量与静态采集的参考重建非常接近。肝穹窿病变的病灶与背景对比度从2.0(无运动校正)提高到5.2(使用我们提出的方法),与静态采集的对比度(5.2)相匹配。相比之下,采用“静态”衰减校正的运动建模产生的对比度较低,为3.5。在患者数据集中,所提出的方法成功地减少了肺部和肝脏病变的运动伪影,并减轻了衰减伪影,证明病变优于背景分离。结论:我们提出的方法能够重建单一的、高质量的活动图像,该图像经过运动校正,没有衰减伪影,而不需要外部硬件。
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引用次数: 0
Modeling and Measurement of Lead Tip Heating in Implanted Wires with Loops. 植入线圈导线中导线尖端发热的建模与测量。
Pub Date : 2024-12-19
Lydia J Bardwell Speltz, Seung-Kyun Lee, Yunhong Shu, Matt A Bernstein

Purpose: To theoretically and experimentally study implant lead tip heating caused by radiofrequency (RF) power deposition in different wire configurations that contain loop(s).

Methods: Maximum temperature rise caused by RF heating was measured at 1.5T on 20 insulated, capped wires with various loop and straight segment configurations. The experimental results were compared with predictions from the previously reported simple exponential and the adapted transmission line models, as well as with a long-wavelength approximation.

Results: Both models effectively predicted the trends in lead tip temperature rise for all the wire configurations, with the adapted transmission line model showing superior accuracy. For superior/inferior (S/I)-oriented wires, increasing the number of loops decreased the overall heating. However, when wires were oriented right/left (R/L) where the x-component of the electric field is negligible, additional loops increased the overall heating.

Conclusion: The simple exponential and the adapted transmission line models previously developed for, and tested on, straight wires require no additional terms or further modification to account for RF heating in a variety of loop configurations. These results extend the models' usefulness to manage implanted device lead tip heating and provide theoretical insight regarding the role of loops and electrical lengths in managing RF safety of implanted devices.

目的:从理论上和实验上研究射频(RF)功率沉积在包含环路的不同导线结构中引起的植入导线尖端加热。方法:对20根不同回路和直段配置的绝缘包封导线在1.5T下测量射频加热引起的最高温升。实验结果与先前报道的简单指数模型和适应的传输线模型的预测结果以及长波长近似进行了比较。结果:两种模型均能有效预测所有导线配置下引线尖端温升趋势,其中采用的传输线模型精度更高。对于优质/劣质(S/I)定向导线,增加回路数量降低了整体加热。然而,当电线向右/左(R/L)方向时,电场的x分量可以忽略不计,额外的环路增加了整体加热。结论:简单指数和先前为直线开发并在直线上测试的适应传输线模型不需要额外的条款或进一步修改,以考虑各种环路配置中的射频加热。这些结果扩展了模型在管理植入设备引线尖端加热方面的实用性,并提供了关于回路和电长度在管理植入设备射频安全中的作用的理论见解。
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引用次数: 0
PhosNetVis: A web-based tool for fast kinase-substrate enrichment analysis and interactive 2D/3D network visualizations of phosphoproteomics data. PhosNetVis:一种基于网络的工具,用于快速激酶-底物富集分析和磷酸化蛋白质组学数据的交互式二维/三维网络可视化。
Pub Date : 2024-12-18
Osho Rawal, Berk Turhan, Irene Font Peradejordi, Shreya Chandrasekar, Selim Kalayci, Sacha Gnjatic, Jeffrey Johnson, Mehdi Bouhaddou, Zeynep H Gümüş

Protein phosphorylation involves the reversible modification of a protein (substrate) residue by another protein (kinase). Liquid chromatography-mass spectrometry studies are rapidly generating massive protein phosphorylation datasets across multiple conditions. Researchers then must infer kinases responsible for changes in phosphosites of each substrate. However, tools that infer kinase-substrate interactions (KSIs) are not optimized to interactively explore the resulting large and complex networks, significant phosphosites, and states. There is thus an unmet need for a tool that facilitates user-friendly analysis, interactive exploration, visualization, and communication of phosphoproteomics datasets. We present PhosNetVis, a web-based tool for researchers of all computational skill levels to easily infer, generate and interactively explore KSI networks in 2D or 3D by streamlining phosphoproteomics data analysis steps within a single tool. PhostNetVis lowers barriers for researchers in rapidly generating high-quality visualizations to gain biological insights from their phosphoproteomics datasets. It is available at: https://gumuslab.github.io/PhosNetVis/.

蛋白质磷酸化涉及另一种蛋白质(激酶)对蛋白质(底物)残基的可逆修饰。液相色谱-质谱研究正在快速生成跨越多种条件的海量蛋白质磷酸化数据集。随后,研究人员必须推断出造成每个底物磷酸化位点变化的激酶。然而,推断激酶-底物相互作用(KSI)的工具并没有进行优化,无法以交互方式探索由此产生的庞大而复杂的网络、重要的磷酸位点和状态。因此,我们需要一种工具来促进磷酸化蛋白质组学数据集的用户友好型分析、交互式探索、可视化和交流。我们推出的 PhosNetVis 是一种基于网络的工具,通过简化磷酸化蛋白质组学数据分析步骤,让各种计算技能水平的研究人员都能轻松推断、生成和交互式探索二维或三维的 KSI 网络。PhostNetVis 降低了研究人员快速生成高质量可视化数据集的门槛,使他们能从磷酸化蛋白质组学数据集中获得生物学见解。可在以下网址获取:https://gumuslab.github.io/PhosNetVis/。
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引用次数: 0
GREGoR: Accelerating Genomics for Rare Diseases. 加速罕见疾病的基因组学研究。
Pub Date : 2024-12-18
Moez Dawood, Ben Heavner, Marsha M Wheeler, Rachel A Ungar, Jonathan LoTempio, Laurens Wiel, Seth Berger, Jonathan A Bernstein, Jessica X Chong, Emmanuèle C Délot, Evan E Eichler, Richard A Gibbs, James R Lupski, Ali Shojaie, Michael E Talkowski, Alex H Wagner, Chia-Lin Wei, Christopher Wellington, Matthew T Wheeler, Claudia M B Carvalho, Casey A Gifford, Susanne May, Danny E Miller, Heidi L Rehm, Fritz J Sedlazeck, Eric Vilain, Anne O'Donnell-Luria, Jennifer E Posey, Lisa H Chadwick, Michael J Bamshad, Stephen B Montgomery

Rare diseases are collectively common, affecting approximately one in twenty individuals worldwide. In recent years, rapid progress has been made in rare disease diagnostics due to advances in DNA sequencing, development of new computational and experimental approaches to prioritize genes and genetic variants, and increased global exchange of clinical and genetic data. However, more than half of individuals suspected to have a rare disease lack a genetic diagnosis. The Genomics Research to Elucidate the Genetics of Rare Diseases (GREGoR) Consortium was initiated to study thousands of challenging rare disease cases and families and apply, standardize, and evaluate emerging genomics technologies and analytics to accelerate their adoption in clinical practice. Further, all data generated, currently representing ~7500 individuals from ~3000 families, is rapidly made available to researchers worldwide via the Genomic Data Science Analysis, Visualization, and Informatics Lab-space (AnVIL) to catalyze global efforts to develop approaches for genetic diagnoses in rare diseases (https://gregorconsortium.org/data). The majority of these families have undergone prior clinical genetic testing but remained unsolved, with most being exome-negative. Here, we describe the collaborative research framework, datasets, and discoveries comprising GREGoR that will provide foundational resources and substrates for the future of rare disease genomics.

罕见病总体上很常见,全世界约有二十分之一的人受其影响。近年来,由于DNA测序的进步,开发了新的计算和实验方法来确定基因和遗传变异的优先次序,以及全球临床和遗传数据的交流增加,罕见病诊断取得了快速进展。然而,超过一半被怀疑患有罕见疾病的人缺乏基因诊断。基因组学研究阐明罕见病遗传学(GREGoR)联盟成立,旨在研究数千例具有挑战性的罕见病病例和家族,并应用、标准化和评估新兴的基因组学技术和分析,以加速其在临床实践中的应用。此外,通过基因组数据科学分析、可视化和信息学实验室空间(AnVIL),所有生成的数据(目前代表来自3000个家庭的约7500个个体)将迅速提供给全世界的研究人员,以促进全球开发罕见疾病遗传诊断方法的努力(https://gregorconsortium.org/data)。这些家庭中的大多数已经进行了先前的临床基因检测,但仍然没有解决,大多数是外显子组阴性。在这里,我们描述了合作研究框架、数据集和发现,包括GREGoR,将为罕见疾病基因组学的未来提供基础资源和基础。
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引用次数: 0
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