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Improved Prediction on Heart Transplant Rejection Using Convolutional Autoencoder and Multiple Instance Learning on Whole-Slide Imaging. 利用卷积自动编码器和全切片成像上的多实例学习改进心脏移植排斥反应预测
Yuanda Zhu, May D Wang, Li Tong, Shriprasad R Deshpande

Heart transplant rejection is one major threat for the survival of patients with a heart transplant. Endomyocardial biopsies are effective in showing signs of heart transplant rejection even before patients have any symptoms. Manually examining the tissue samples is costly, time-consuming and error-prone. With recent advances in deep learning (DL) based image processing methods, automatic training and prediction on heart transplant rejection using whole-slide images expect to be promising. This paper develops an advanced pipeline for quality control, feature extraction, clustering and classification. We first implement a stacked convolutional autoencoder to extract feature maps for each tile; we then incorporate multiple instance learning (MIL) with dimensionality reduction and unsupervised clustering prior to classification. Our results show that utilizing unsupervised clustering after feature extraction can achieve higher classification results while preserving the capability for multi-class classification.

心脏移植排斥反应是心脏移植患者生存的一大威胁。心内膜活检能在患者出现任何症状之前有效显示心脏移植排斥反应的迹象。人工检查组织样本成本高、耗时长且容易出错。随着基于深度学习(DL)的图像处理方法的最新进展,使用全切片图像对心脏移植排斥反应进行自动训练和预测将大有可为。本文开发了一种先进的质量控制、特征提取、聚类和分类管道。我们首先实施了一个堆叠卷积自动编码器,以提取每个磁片的特征图;然后,我们在分类前结合了多实例学习 (MIL)、降维和无监督聚类。我们的结果表明,在提取特征后使用无监督聚类可以获得更高的分类结果,同时保留多类分类的能力。
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引用次数: 0
Alterations in Chromatin Folding Patterns in Cancer Variant-Enriched Loci. 癌症变异富集位点中染色质折叠模式的改变。
Alan Perez-Rathke, Samira Mali, Lin Du, Jie Liang

In this study, we focus on the following question: do genomic regions enriched in cancer variant mutations have significantly different chromatin folding patterns? We utilize publicly available Hi-C data to characterize chromatin folding patterns in healthy (GM12878) and cancer (K562) cells based on status of A/B compartmentalization and random vs non-random chromatin physical interactions. We then perform statistical testing to assess if chromatin folding patterns in cancer variant-enriched loci are significantly different from non-enriched loci. Our results indicate that loci with cancer variant status have significantly altered (FDR < 0.05) chromatin folding patterns.

在这项研究中,我们关注以下问题:富集癌症变异突变的基因组区域是否具有显著不同的染色质折叠模式?我们利用公开可用的Hi-C数据,基于A/B区隔状态和随机与非随机染色质物理相互作用,表征健康(GM12878)和癌症(K562)细胞的染色质折叠模式。然后,我们进行统计检验,以评估癌症变异富集位点的染色质折叠模式是否与非富集位点显著不同。我们的研究结果表明,具有癌症变异状态的位点显著改变了染色质折叠模式(FDR < 0.05)。
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引用次数: 4
ECGNET: Learning where to attend for detection of atrial fibrillation with deep visual attention. ECGNET:通过深度视觉注意力学习检测心房颤动时的注意点。
Seyed Sajad Mousavi, Fatemah Afghah, Abolfazl Razi, U Rajendra Acharya

The complexity of the patterns associated with atrial fibrillation (AF) and the high level of noise affecting these patterns have significantly limited the application of current signal processing and shallow machine learning approaches to accurately detect this condition. Deep neural networks have shown to be very powerful to learn the non-linear patterns in various problems such as computer vision tasks. While deep learning approaches have been utilized to learn complex patterns related to the presence of AF in electrocardiogram (ECG) signals, they can considerably benefit from knowing which parts of the signal is more important to focus on during learning. In this paper, we introduce a two-channel deep neural network to more accurately detect the presence of AF in the ECG signals. The first channel takes in an ECG signal and automatically learns where to attend for detection of AF. The second channel simultaneously takes in the same ECG signal to consider all features of the entire signal. Besides improving detection accuracy, this model can guide the physicians via visualization that what parts of the given ECG signal are important to attend while trying to detect atrial fibrillation. The experimental results confirm that the proposed model significantly improves the performance of AF detection on well-known MIT-BIH AF database with 5-s ECG segments (achieved a sensitivity of 99.53%, specificity of 99.26% and accuracy of 99.40%).

心房颤动(房颤)相关模式的复杂性和影响这些模式的高水平噪声极大地限制了当前信号处理和浅层机器学习方法在准确检测这种情况方面的应用。在计算机视觉任务等各种问题中,深度神经网络在学习非线性模式方面已显示出非常强大的功能。虽然深度学习方法已被用于学习与心电图(ECG)信号中是否存在房颤有关的复杂模式,但在学习过程中,如果能知道信号的哪些部分更重要,就能大大受益。在本文中,我们引入了双通道深度神经网络,以更准确地检测心电图信号中是否存在房颤。第一个通道接收心电信号,并自动学习检测房颤时应关注的部分。第二个通道同时接收同一心电信号,以考虑整个信号的所有特征。除了提高检测准确率外,该模型还能通过可视化引导医生在检测心房颤动时关注给定心电图信号的哪些部分。实验结果证实,在著名的 MIT-BIH 房颤数据库中,所提出的模型显著提高了 5 秒心电图片段的房颤检测性能(灵敏度达到 99.53%,特异度达到 99.26%,准确度达到 99.40%)。
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引用次数: 0
Prioritization of Cognitive Assessments in Alzheimer's Disease via Learning to Rank using Brain Morphometric Data. 通过使用脑形态测量数据学习排序来确定阿尔茨海默病认知评估的优先级。
Bo Peng, Xiaohui Yao, Shannon L Risacher, Andrew J Saykin, Li Shen, Xia Ning

We propose an innovative machine learning paradigm enabling precision medicine for prioritizing cognitive assessments according to their relevance to Alzheimer's disease at the individual patient level. The paradigm tailors the cognitive biomarker discovery and cognitive assessment selection process to the brain morphometric characteristics of each individual patient. We implement this paradigm using a newly developed learning-to-rank method PLTR. Our empirical study on the ADNI data yields promising results to identify and prioritize individual-specific cognitive biomarkers as well as cognitive assessment tasks based on the individual's structural MRI data. The resulting top ranked cognitive biomarkers and assessment tasks have the potential to aid personalized diagnosis and disease subtyping.

我们提出了一种创新的机器学习范式,使精准医学能够根据个体患者水平上与阿尔茨海默病的相关性来优先考虑认知评估。该范式根据每个个体患者的大脑形态特征定制认知生物标志物发现和认知评估选择过程。我们使用一种新开发的学习排序方法PLTR来实现这种范式。我们对ADNI数据的实证研究在识别和优先考虑个体特异性认知生物标志物以及基于个体结构MRI数据的认知评估任务方面取得了有希望的结果。由此产生的排名靠前的认知生物标志物和评估任务有可能帮助个性化诊断和疾病亚型。
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引用次数: 2
DeepDDK: A Deep Learning based Oral-Diadochokinesis Analysis Software. DeepDDK:一个基于深度学习的口头对话分析软件。
Yang Yang Wang, Ke Gao, Yunxin Zhao, Mili Kuruvilla-Dugdale, Teresa E Lever, Filiz Bunyak

Oromotor dysfunction caused by neurological disorders can result in significant speech and swallowing impairments. Current diagnostic methods to assess oromotor function are subjective and rely on perceptual judgments by clinicians. In particular, the widely used oral-diadochokinesis (oral-DDK) test, which requires rapid, alternate repetitions of speech-based syllables, is conducted and interpreted differently among clinicians. It is therefore prone to inaccuracy, which results in poor test reliability and poor clinical application. In this paper, we present a deep learning based software to extract quantitative data from the oral DDK signal, thereby transforming it into an objective diagnostic and treatment monitoring tool. The proposed software consists of two main modules: a fully automated syllable detection module and an interactive visualization and editing module that allows inspection and correction of automated syllable units. The DeepDDK software was evaluated on speech files corresponding to 9 different DDK syllables (e.g., "Pa", "Ta", "Ka"). The experimental results show robustness of both syllable detection and localization across different types of DDK speech tasks.

由神经系统疾病引起的运动障碍可导致严重的语言和吞咽障碍。目前评估运动功能的诊断方法是主观的,依赖于临床医生的感知判断。特别是,广泛使用的口头递调(oral-DDK)测试,需要快速,交替重复基于语音的音节,在临床医生之间进行和解释不同。因此,它容易出现不准确,从而导致测试可靠性差,临床应用不佳。在本文中,我们提出了一个基于深度学习的软件,从口腔DDK信号中提取定量数据,从而将其转化为客观的诊断和治疗监测工具。所提出的软件包括两个主要模块:一个全自动音节检测模块和一个交互式可视化和编辑模块,允许检查和纠正自动音节单位。DeepDDK软件对9个不同的DDK音节(如“Pa”、“Ta”、“Ka”)对应的语音文件进行了评估。实验结果表明,该方法在不同类型的DDK语音任务中,音节检测和定位都具有鲁棒性。
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引用次数: 4
A Social Cognitive Theory-based Framework for Monitoring Medication Adherence Applied to Endocrine Therapy in Breast Cancer Survivors. 基于社会认知理论的用药依从性监测框架应用于乳腺癌幸存者的内分泌治疗。
Mehdi Boukhechba, Sonia Baee, Alicia L Nobles, Jiaqi Gong, Kristen Wells, Laura E Barnes

Poor adherence to long-term therapies for chronic diseases, such as cancer, compromises effectiveness of treatment and increases the likelihood of disease progression, making medication adherence a critical issue in population health. While the field has documented many eers to adherence to medication, it has also come up with few efficacious solutions to medication adherence, indicating that new and innovative approaches are needed. In this paper, we evaluate medication-taking behaviors based on social cognitive theory (SCT), presenting patterns of adherence stratified across SCT constructs in 33 breast cancer survivors over an 8-month period. Findings indicate that medication adherence is a very personal experience influenced by many simultaneously interacting factors, and a deeper contextual understanding is needed to understand and develop interventions targeting non-adherence.

对于癌症等慢性病的长期治疗,如果依从性差,就会影响治疗效果,增加疾病恶化的可能性,因此,坚持用药是人口健康的一个关键问题。虽然该领域已经记录了许多影响坚持用药的因素,但也没有提出什么有效的解决方案来解决坚持用药的问题,这表明需要新的创新方法。在本文中,我们基于社会认知理论(SCT)对服药行为进行了评估,介绍了 33 名乳腺癌幸存者在 8 个月的服药模式,并根据 SCT 的不同构建对服药模式进行了分层。研究结果表明,服药依从性是一种非常个人化的体验,受到许多同时相互作用的因素的影响,因此需要对背景有更深入的了解,才能理解和制定针对不依从性的干预措施。
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引用次数: 0
Quantification of Biological Responses as Predictors of Cognitive Outcome after Developmental TBI. 定量生物学反应作为发展性脑损伤后认知预后的预测因子。
Saman Sargolzaei, Yan Cai, Deborah Lee, Neil G Harris, Christopher C Giza

Successful translational studies within the field of Traumatic Brain Injury (TBI) are concerned with determining reliable markers of injury outcome at chronic time points. Determination of injury severity following Fluid Percussion Injury (FPI) has long been limited to the measured atmospheric pressure associated with the delivered pulse. Duration of unresponsiveness to toe pinch (unconsciousness) was next introduced as an extra marker of injury severity. The current study is an effort to assess the utilization of acute injury-induced biological responses (duration of toe pinch unresponsiveness, percent body weight change, quantification of brain edema, and apnea duration) to predict cognitive performance at a subacute time point following developmental brain injury. Cognitive performance, when measured at a subacute phase, after developmental FPI was negatively correlated with the following variables, duration of toe pinch unresponsiveness, percent weight change, and quantified level of brain edema. These finding suggest the potential utilization of reliable severity assessment of injury-induced biological responses in determining outcome measures at subacute time points.

创伤性脑损伤(TBI)领域成功的转化研究涉及确定慢性时间点损伤结果的可靠标记。长期以来,液体撞击损伤(FPI)后损伤严重程度的确定一直局限于与传递脉冲相关的测量大气压力。对脚趾捏无反应的持续时间(无意识)接下来被引入作为损伤严重程度的额外标记。目前的研究旨在评估急性损伤诱导的生物反应(脚趾无反应持续时间、体重变化百分比、脑水肿量化和呼吸暂停持续时间)在发育性脑损伤后亚急性时间点的认知表现。当在亚急性期测量时,发育FPI后的认知表现与以下变量负相关:脚趾捏无反应的持续时间、体重变化百分比和脑水肿量化水平。这些发现表明,在确定亚急性时间点的结局措施时,对损伤诱导的生物反应进行可靠的严重程度评估是潜在的。
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引用次数: 1
Activity and Circadian Rhythm of Sepsis Patients in the Intensive Care Unit. 重症监护室脓毒症患者的活动和昼夜节律。
Anis Davoudi, Duane B Corbett, Tezcan Ozrazgat-Baslanti, Azra Bihorac, Scott C Brakenridge, Todd M Manini, Parisa Rashidi

Early mobilization of critically ill patients in the Intensive Care Unit (ICU) can prevent adverse outcomes such as delirium and post-discharge physical impairment. To date, no studies have characterized activity of sepsis patients in the ICU using granular actigraphy data. This study characterizes the activity of sepsis patients in the ICU to aid in future mobility interventions. We have compared the actigraphy features of 24 patients in four groups: Chronic Critical Illness (CCI) sepsis patients in the ICU, Rapid Recovery (RR) sepsis patients in the ICU, non-sepsis ICU patients (control-ICU), and healthy subjects. We used a total of 15 statistical and circadian rhythm features extracted from the patients' actigraphy data collected over a five-day period. Our results show that the four groups are significantly different in terms of activity features. In addition, we observed that the CCI and control-ICU patients show less regularity in their circadian rhythm compared to the RR patients. These results show the potential of using actigraphy data for guiding mobilization practices, classifying sepsis recovery subtype, as well as for tracking patients' recovery.

重症监护病房(ICU)危重患者的早期动员可以预防谵妄和出院后身体损伤等不良后果。到目前为止,还没有研究使用颗粒活动数据来描述ICU脓毒症患者的活动。本研究描述了脓毒症患者在ICU的活动,以帮助未来的活动干预。我们将24例患者分为四组:ICU的慢性危重症(CCI)脓毒症患者、ICU的快速恢复(RR)脓毒症患者、非脓毒症ICU患者(对照-ICU)和健康受试者。我们总共使用了15个统计和昼夜节律特征,这些特征是从5天内收集的患者活动记录数据中提取的。我们的研究结果表明,四组在活动特征上存在显著差异。此外,我们观察到,与RR患者相比,CCI和对照icu患者的昼夜节律规律性较差。这些结果显示了使用活动图数据指导动员实践,分类败血症恢复亚型以及跟踪患者恢复的潜力。
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引用次数: 7
On quantification of geometry and topology of protein pockets and channels for assessing mutation effects. 量化蛋白质口袋和通道的几何和拓扑结构以评估突变效应。
Wei Tian, Jie Liang

Geometric and topological features of proteins such as voids, pockets and channels are important for protein functions. We discuss a method for visualizing protein pockets and channels based on orthogonal spheres computed from alpha shapes of the protein structures, and how metric properties of channel surfaces can be mapped. In addition, we discuss how structurally prominent sites, such as constriction sties in channels, can be computed, which may help to understand protein functions and mutation effects, with implications in developing novel therapeutic interventions.

蛋白质的几何和拓扑特征(如空隙、口袋和通道)对蛋白质功能非常重要。我们讨论了一种基于正交球的蛋白质口袋和通道可视化方法,该方法由蛋白质结构的阿尔法形状计算得出,还讨论了如何映射通道表面的度量特性。此外,我们还讨论了如何计算结构上的突出位点,如通道中的收缩位点,这可能有助于了解蛋白质的功能和突变效应,对开发新型治疗干预措施具有重要意义。
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引用次数: 0
A General Method for Predicting Amino Acid Residues Experiencing Hydrogen Exchange. 预测发生氢交换的氨基酸残基的一般方法。
Boshen Wang, Alan Perez-Rathke, Renhao Li, Jie Liang

Information on protein hydrogen exchange can help delineate key regions involved in protein-protein interactions and provides important insight towards determining functional roles of genetic variants and their possible mechanisms in disease processes. Previous studies have shown that the degree of hydrogen exchange is affected by hydrogen bond formations, solvent accessibility, proximity to other residues, and experimental conditions. However, a general predictive method for identifying residues capable of hydrogen exchange transferable to a broad set of proteins is lacking. We have developed a machine learning method based on random forest that can predict whether a residue experiences hydrogen exchange. Using data from the Start2Fold database, which contains information on 13,306 residues (3,790 of which experience hydrogen exchange and 9,516 which do not exchange), our method achieves good performance. Specifically, we achieve an overall out-of-bag (OOB) error, an unbiased estimate of the test set error, of 20.3 percent. Using a randomly selected test data set consisting of 500 residues experiencing hydrogen exchange and 500 which do not, our method achieves an accuracy of 0.79, a recall of 0.74, a precision of 0.82, and an F1 score of 0.78.

有关蛋白质氢交换的信息有助于划定蛋白质-蛋白质相互作用的关键区域,并为确定遗传变异的功能作用及其在疾病过程中的可能机制提供重要的洞察力。以往的研究表明,氢交换的程度受氢键的形成、溶剂的可及性、与其他残基的接近程度以及实验条件的影响。然而,目前还缺乏一种通用的预测方法来识别能够进行氢交换的残基,并将其应用于大量蛋白质。我们开发了一种基于随机森林的机器学习方法,可以预测残基是否发生氢交换。Start2Fold 数据库包含 13,306 个残基(其中 3,790 个会发生氢交换,9,516 个不会发生氢交换)的信息。具体来说,我们的总体袋外(OOB)误差(测试集误差的无偏估计值)为 20.3%。使用随机选取的测试数据集(包括 500 个发生氢交换的残基和 500 个未发生氢交换的残基),我们的方法获得了 0.79 的准确率、0.74 的召回率、0.82 的精确率和 0.78 的 F1 分数。
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引用次数: 0
期刊
... IEEE-EMBS International Conference on Biomedical and Health Informatics. IEEE-EMBS International Conference on Biomedical and Health Informatics
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