Modeling of dynamical systems through deep learning

This review presents a modern perspective on dynamical systems in the context of current goals and open challenges. In particular, our review focuses on the key challenges of discovering dynamics from data and finding data-driven representations that make nonlinear systems amenable to linear analysis. We explore various challenges in modern dynamical systems, along with emerging techniques in data science and machine learning to tackle them. The two chief challenges are (1) nonlinear dynamics and (2) unknown or partially known dynamics. Machine learning is providing new and powerful techniques for both challenges. Dimensionality reduction methods are used for projecting dynamical methods in reduced form, and these methods perform computational efficiency on real-world data. Data-driven models drive to discover the governing equations and give laws of physics. The identification of dynamical systems through deep learning techniques succeeds in inferring physical systems. Machine learning provides advanced new and powerful algorithms for nonlinear dynamics. Advanced deep learning methods like autoencoders, recurrent neural networks, convolutional neural networks, and reinforcement learning are used in modeling of dynamical systems.     

血清TM、P-selectin、HDL-C以及凝血功能指标与创伤性骨折患者术后深静脉血栓形成的关系研究

摘要 目的：探讨血清血栓调节蛋白（TM）、P-选择素（P-selectin）、高密度脂蛋白（HDL-C）以及凝血功能指标与创伤性骨折患者术后深静脉血栓形成（DVT）的关系。方法：选择2018年1月至2020年1月我院收治的术后发生DVT的创伤性骨折患者100例作为DVT组,同期术后未发生DVT的创伤性骨折患者100例作为无DVT组,比较两组血清TM、P-selectin、HDL-C、血浆凝血功能指标[凝血酶时间（TT）、凝血酶原时间（PT）、活化部分凝血酶时间（APTT）、纤维蛋白原（FIB）、D-二聚体（D-D）],应用Pearson相关性分析血清TM、P-selectin、HDL-C与凝血功能指标的相关性,应用多因素Logistic回归分析创伤性骨折患者术后DVT的影响因素。结果：DVT组血清TM、P-selectin、血浆D-D、FIB水平、年龄≥60岁比例高于无DVT组,血清HDL-C水平低于无DVT组（P＜0.05）。DVT组血清TM和P-selectin与血浆D-D、FIB呈正相关（P＜0.05）,血清HDL-C与血浆D-D、FIB呈负相关（P＜0.05）。多因素Logistic回归分析显示,年龄≥60岁、血清TM≥9.50 IU/mL、P-selectin ≥70.00 ng/mL、HDL-C<1.00 mmol/L、血浆D-D≥700.00 μg/L、FIB≥4.00 g/L是创伤性骨折患者术后DVT的危险因素（P＜0.05）。结论：创伤性骨折患者术后发生DVT患者血清TM、P-selectin较无DVT患者升高,HDL-C较无DVT患者降低,联合检测血清TM、P-selectin、HDL-C和凝血功能指标可能有助于降低DVT的发生风险。     

Large-scale pharmacogenomic studies and drug response prediction for personalized cancer medicine

The response rate of most anti-cancer drugs is limited because of the high heterogeneity of cancer and the complex mechanism of drug action. Personalized treatment that stratifies patients into subgroups using molecular biomarkers is promising to improve clinical benefit. With the accumulation of preclinical models and advances in computational approaches of drug response prediction, pharmacogenomics has made great success over the last 20 years and is increasingly used in the clinical practice of personalized cancer medicine. In this article, we first summarize FDA-approved pharmacogenomic biomarkers and large-scale pharmacogenomic studies of preclinical cancer models such as patient-derived cell lines, organoids, and xenografts. Furthermore, we comprehensively review the recent developments of computational methods in drug response prediction, covering network, machine learning, and deep learning technologies and strategies to evaluate immunotherapy response. In the end, we discuss challenges and propose possible solutions for further improvement.     

基于深度学习与多层次信息融合的药物靶标亲和力预测*

药物研发是非常重要但也十分耗费人力物力的过程。利用计算机辅助预测药物与蛋白质亲和力的方法可以极大地加快药物研发过程。药物靶标亲和力预测的关键在于对药物和蛋白质进行准确详细地信息表征。提出一种基于深度学习与多层次信息融合的药物靶标亲和力的预测模型,试图通过综合药物与蛋白质的多层次信息,来获得更好的预测表现。首先将药物表述成分子图和扩展连接指纹两种形式,分别利用图卷积神经网络模块和全连接层进行学习;其次将蛋白质序列和蛋白质K-mer特征分别输入卷积神经网络模块和全连接层来学习蛋白质潜在特征;随后将4个通道学习到的特征进行融合,再利用全连接层进行预测。在两个基准药物靶标亲和力数据集上验证了所提方法的有效性,并与其他已有模型作对比研究。结果说明提出的模型相比基准模型能得到更好的预测性能,表明提出的综合药物与蛋白质多层次信息的药物靶标亲和力预测策略是有效的。     

Multiomics metabolic and epigenetics regulatory network in cancer: A systems biology perspective

Genetic, epigenetic, and metabolic alterations are all hallmarks of cancer. However, the epigenome and metabolome are both highly complex and dynamic biological networks in vivo. The interplay between the epigenome and metabolome contributes to a biological system that is responsive to the tumor microenvironment and possesses a wealth of unknown biomarkers and targets of cancer therapy. From this perspective, we first review the state of high-throughput biological data acquisition(i.e. multiomics data)and analysis(i.e. computational tools) and then propose a conceptual in silico metabolic and epigenetic regulatory network(MER-Net) that is based on these current high-throughput methods. The conceptual MER-Net is aimed at linking metabolomic and epigenomic networks through observation of biological processes, omics data acquisition, analysis of network information, and integration with validated database knowledge. Thus, MER-Net could be used to reveal new potential biomarkers and therapeutic targets using deep learning models to integrate and analyze large multiomics networks. We propose that MER-Net can serve as a tool to guide integrated metabolomics and epigenomics research or can be modified to answer other complex biological and clinical questions using multiomics data.     

Major depressive disorder diagnosis based on effective connectivity in EEG signals: a convolutional neural network and long short-term memory approach

Deep learning techniques have recently made considerable advances in the field of artificial intelligence. These methodologies can assist psychologists in early diagnosis of mental disorders and preventing severe trauma. Major Depression Disorder (MDD) is a common and serious medical condition whose exact manifestations are not fully understood. So, early discovery of MDD patients helps to cure or limit the adverse effects. Electroencephalogram (EEG) is prominently used to study brain diseases such as MDD due to having high temporal resolution information, and being a noninvasive, inexpensive and portable method. This paper has proposed an EEG-based deep learning framework that automatically discriminates MDD patients from healthy controls. First, the relationships among EEG channels in the form of effective brain connectivity analysis are extracted by Generalized Partial Directed Coherence (GPDC) and Direct directed transfer function (dDTF) methods. A novel combination of sixteen connectivity methods (GPDC and dDTF in eight frequency bands) was used to construct an image for each individual. Finally, the constructed images of EEG signals are applied to the five different deep learning architectures. The first and second algorithms were based on one and two-dimensional convolutional neural network (1DCNN–2DCNN). The third method is based on long short-term memory (LSTM) model, while the fourth and fifth algorithms utilized a combination of CNN with LSTM model namely, 1DCNN-LSTM and 2DCNN-LSTM. The proposed deep learning architectures automatically learn patterns in the constructed image of the EEG signals. The efficiency of the proposed algorithms is evaluated on resting state EEG data obtained from 30 healthy subjects and 34 MDD patients. The experiments show that the 1DCNN-LSTM applied on constructed image of effective connectivity achieves best results with accuracy of 99.24% due to specific architecture which captures the presence of spatial and temporal relations in the brain connectivity. The proposed method as a diagnostic tool is able to help clinicians for diagnosing the MDD patients for early diagnosis and treatment.     

A novel fast kilovoltage switching dual-energy CT with deep learning: Accuracy of CT number on virtual monochromatic imaging and iodine quantification

PurposeA novel fast kilovoltage switching dual-energy CT with deep learning [Deep learning based-spectral CT (DL-Spectral CT)], which generates a complete sinogram for each kilovolt using deep learning views that complement the measured views at each energy, was commercialized in 2020. The purpose of this study was to evaluate the accuracy of CT numbers in virtual monochromatic images (VMIs) and iodine quantifications at various radiation doses using DL-Spectral CT.Materials and methodsTwo multi-energy phantoms (large and small) using several rods representing different materials (iodine, calcium, blood, and adipose) were scanned by DL-Spectral CT at varying radiation doses. Images were reconstructed using three reconstruction parameters (body, lung, bone). The absolute percentage errors (APEs) for CT numbers on VMIs at 50, 70, and 100 keV and iodine quantification were compared among different radiation dose protocols.ResultsThe APEs of the CT numbers on VMIs were <15% in both the large and small phantoms, except at the minimum dose in the large phantom. There were no significant differences among radiation dose protocols in computed tomography dose index volumes of 12.3 mGy or larger. The accuracy of iodine quantification provided by the body parameter was significantly better than those obtained with the lung and bone parameters. Increasing the radiation dose did not always improve the accuracy of iodine quantification, regardless of the reconstruction parameter and phantom size.ConclusionThe accuracy of iodine quantification and CT numbers on VMIs in DL-Spectral CT was not affected by the radiation dose, except for an extremely low radiation dose for body size.     

Deep Learning Using Havrda-Charvat Entropy for Classification of Pulmonary Optical Endomicroscopy

1) ObjectivePulmonary optical endomicroscopy (POE) is an imaging technology in real time. It allows to examine pulmonary alveoli at a microscopic level. Acquired in clinical settings, a POE image sequence can have as much as 25% of the sequence being uninformative frames (i.e. pure-noise and motion artifacts). For future data analysis, these uninformative frames must be first removed from the sequence. Therefore, the objective of our work is to develop an automatic detection method of uninformative images in endomicroscopy images.2) Material and methodsWe propose to take the detection problem as a classification one. Considering advantages of deep learning methods, a classifier based on CNN (Convolutional Neural Network) is designed with a new loss function based on Havrda-Charvat entropy which is a parametrical generalization of the Shannon entropy. We propose to use this formula to get a better hold on all sorts of data since it provides a model more stable than the Shannon entropy.3) ResultsOur method is tested on one POE dataset including 3895 distinct images and is showing better results than using Shannon entropy and behaves better with regard to the problem of overfitting. We obtain 70% of accuracy with Shannon entropy versus 77 to 79% with Havrda-Charvat.4) ConclusionWe can conclude that Havrda-Charvat entropy is better suited for restricted and or noisy datasets due to its generalized nature. It is also more suitable for classification in endomicroscopy datasets.     

An Approach Based on Mutually Informed Neural Networks to Optimize the Generalization Capabilities of Decision Support Systems Developed for Heart Failure Prediction

Available clinical methods for heart failure (HF) diagnosis are expensive and require a high-level of experts intervention. Recently, various machine learning models have been developed for the prediction of HF where most of them have an issue of over-fitting. Over-fitting occurs when machine learning based predictive models show better performance on the training data yet demonstrate a poor performance on the testing data and the other way around. Developing a machine learning model which is able to produce generalization capabilities (such that the model exhibits better performance on both the training and the testing data sets) could overall minimize the prediction errors. Hence, such prediction models could potentially be helpful to cardiologists for the effective diagnose of HF. This paper proposes a two-stage decision support system to overcome the over-fitting issue and to optimize the generalization factor. The first stage uses a mutual information based statistical model while the second stage uses a neural network. We applied our approach to the HF subset of publicly available Cleveland heart disease database. Our experimental results show that the proposed decision support system has optimized the generalization capabilities and has reduced the mean percent error (MPE) to 8.8% which is significantly less than the recently published studies. In addition, our model exhibits a 93.33% accuracy rate which is higher than twenty eight recently developed HF risk prediction models that achieved accuracy in the range of 57.85% to 92.31%. We can hope that our decision support system will be helpful to cardiologists if deployed in clinical setup.