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Overview of Machine Learning Methods for Genome-Wide Association Analysis 全基因组关联分析的机器学习方法综述
Minzhu Xie, Fang Liu
Genome-wide association studies (GWAS) is an effective way to reveal the pathogenic genes of complex diseases by analyzing the genotype information and related disease phenotype information on the SNP loci of the whole genome of a large number of living organisms. Machine learning (ML) is a method that allows computers to simulate human cognitive processes to solve problems. The advantage of using machine learning methods to carry out genome-wide association analysis research is that it does not require false anchor points or gene-gene interaction models in advance Instead of exhaustive search, computer algorithms that simulate human cognitive processes can learn from a large amount of data to discover the ability of nonlinear high-dimensional gene-gene interactions. In recent years, a large number of machine learning methods have been used in the study of genome-wide association analysis. This article will briefly introduct these methods.
全基因组关联研究(genome -wide association studies, GWAS)是通过分析大量生物体全基因组SNP位点上的基因型信息和相关疾病表型信息,揭示复杂疾病致病基因的有效途径。机器学习(ML)是一种允许计算机模拟人类认知过程来解决问题的方法。利用机器学习方法开展全基因组关联分析研究的优势在于,它不需要事先建立假锚点或基因-基因相互作用模型,而是通过模拟人类认知过程的计算机算法,从大量数据中学习,发现非线性高维基因-基因相互作用的能力。近年来,大量的机器学习方法被用于全基因组关联分析的研究。本文将简要介绍这些方法。
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引用次数: 0
Identification of the C2H2 Type Zinc Finger Transcription Factor Family in Aspergillus Flavus and Aspergillus Oryzae and Their Expression Profiles in Aspergillus Oryzae 黄曲霉和米曲霉C2H2型锌指转录因子家族的鉴定及其在米曲霉中的表达谱
Qing Liu, Jianhua Huang, B. He
C2H2 zinc protein transcription family members play an important biological role in the mitotic bacteria. The study identified 25 and 26 families of C2H2 zinc dead, respectively, in Aspergillus flavus and Aspergillus oryzae genome databases. According to phytogenetics and fantasy analysis, the families of C2H2 zinc can be divided into four subfamilies. Genes in this family are distributed across eight chromosomes. In addition, the relationship of structure and function of C2H2 zinc transfer factors was comprehensively analyzed to intuitively understand the features of protective drawings. It also analyzed the expression profiles of the transcription factors of C2H2 under salt stress treatment and different growth phase. As a result, under salt stress treatment, C2H2 zinc has a relatively low algebraic and downward regulation of transcription factors. This work has a deeper understanding of the evolution and function of C2H2 zinc transcription factors in Aspergillus flavus and Aspergillus oryzae, and helps improve gene improvement of strains to adapt to complex surroundings.
C2H2锌蛋白转录家族成员在有丝分裂细菌中起着重要的生物学作用。本研究在黄曲霉和米曲霉基因组数据库中分别鉴定出25个和26个C2H2锌死亡家族。根据植物遗传学和幻想分析,C2H2锌属可分为4个亚科。这个家族的基因分布在8条染色体上。此外,综合分析了C2H2锌传递因子的结构与功能关系,直观地了解了防护图的特点。分析了盐胁迫处理和不同生长时期C2H2转录因子的表达谱。因此,在盐胁迫处理下,C2H2锌对转录因子的代数调控和下调作用相对较低。本工作对C2H2锌转录因子在黄曲霉和米曲霉中的进化和功能有了更深入的了解,有助于改进菌株的基因改良,以适应复杂的环境。
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引用次数: 0
Thermal Dose Images Enhance the Prediction of Local Tumor Progression After Multimode Ablation 多模消融后热剂量图像增强局部肿瘤进展预测
Xinyi Wang, Jianlong Yang, A. Zhang, L. Xu
The multimode ablation which uses Radiofrequency heating after a pre-freezing process to treat the tumor, has shown significantly improved therapeutic effects and enhanced antitumor immune response. Unlike surgery, the ablated lesion remains in the body after treatment. Effective treatment evaluation is important to assess the immediate outcome and to monitor disease status over time. We proposed a novel postoperative assessment method combined radiomics features and thermal dose information. Patients with hepatocellular carcinoma and colorectal liver metastases from October 2016 to February 2019 were retrospectively studied. Based on the recorded parameters, intraoperative thermal dose distribution were constructed by a two-step "simulation-fusion" method, taking into account the superposition of energy from multiple treatments. Radiomic features of the tumor, such as grayscale, geometry and texture, were collected from preoperative and postoperative MRI, intraoperative CT and the thermal dose maps. The random survival forest model with input of clinical records, preoperative tumor features and intraoperative thermal dose features was the most competitive (C-index=0.92±0.012, iAUC=0.889, iBS=0.041). The grouping based on risk scores allows quick identification of the levels of long term risk after surgery. Based on the predicted survival probability function, clinicians can predictably enhance monitoring and perform other adjuvant therapies.
多模式消融术采用预冷冻后射频加热治疗肿瘤,治疗效果明显改善,抗肿瘤免疫反应增强。与手术不同,消融后的病变在治疗后仍留在体内。有效的治疗评估对于评估即时结果和监测疾病状态很重要。我们提出了一种结合放射组学特征和热剂量信息的新型术后评估方法。回顾性研究2016年10月至2019年2月的肝细胞癌和结直肠肝转移患者。基于记录的参数,考虑到多个治疗过程的能量叠加,采用两步“模拟-融合”方法构建术中热剂量分布。术前、术后MRI、术中CT及热剂量图采集肿瘤放射学特征,如灰度、几何、纹理等。输入临床记录、术前肿瘤特征和术中热剂量特征的随机生存森林模型最具竞争力(C-index=0.92±0.012,iAUC=0.889, iBS=0.041)。基于风险评分的分组可以快速识别手术后的长期风险水平。根据预测的生存概率函数,临床医生可以预测地加强监测和实施其他辅助治疗。
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引用次数: 0
Computational Prediction of N6-methyladenosine (m6A) RNA Methylation in SARS-CoV-2 Viral Transcripts SARS-CoV-2病毒转录物中n6 -甲基腺苷(m6A) RNA甲基化的计算预测
Qingru Xu, Xiangyu Wu, Jia Meng
SARS-CoV-2 caused atypical pneumonia (COVID-19) is an ongoing pandemic that seriously threat the global public health. Many people die from this disease with severe symptoms. The most prevalent m6A RNA modification may be involved in by assisting the virus escaping from the host cell immune system attack. We provided here the first computational prediction study of RNA methylation sites in SARS-CoV-2. Based on virus sequence information, we predict the potential virus m6A sites and hope to make anyhow contributions to this unprecedented situation. As a result, we found 27 most frequent m6A sequences (41 bp) in SARS-CoV-2, and two of them are quite near to the spike protein stop codon position.
SARS-CoV-2引起的非典型肺炎(COVID-19)是一种严重威胁全球公共卫生的持续大流行。许多人死于这种疾病,症状严重。最常见的m6A RNA修饰可能是通过帮助病毒逃避宿主细胞免疫系统的攻击。我们在这里提供了SARS-CoV-2中RNA甲基化位点的首次计算预测研究。根据病毒序列信息,预测潜在的病毒m6A位点,希望对这一前所未有的局面有所贡献。结果,我们在SARS-CoV-2中发现了27个最常见的m6A序列(41 bp),其中两个序列非常接近刺突蛋白停止密码子位置。
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引用次数: 0
Fungicidal Mechanism of Ortho-Phthaldialdehyde-benzyldlmethyldodecylammonlum Chloride as A Disinfectant Against Candida Albicans 邻苯二醛-苄基甲基十二烷基氯化铵对白色念珠菌的杀菌作用机理
Chunxia Li, X. Kong, Minjia Wang, J. Yi, Jinghan Yi, Z. Deng, Qin Chen
Candida albicans is a common fungal pathogen, which is resistant to most commonly used disinfectants. It can cause serious interference in more than ten countries and even lead to death, so it is considered to be a serious global health threat. Obviously, in order to effectively control the spread of Candida albicans, the development of an efficient disinfectant is an important strategy. In this research, the fungicidal mechanism of ODB for Candida albicans was investigated through membrane fluidity, membrane integrity, protein leakage, functional changes of cell and mitochondria. ODB can affect fluidity and integrity of the cell membrane of Candida albicans, result in large amount of ions, proteins, glycerol, reactive oxygen species, ATP and DNA to leak, lower or dysfunction mitochondria by deteriorating cell ability to produce ATP or to make use of ATP, and less DNA content. And all these changes in structure and function are the main causes of the ultimate death of Candida albicans.
白色念珠菌是一种常见的真菌病原体,它对大多数常用的消毒剂具有耐药性。它可以在十多个国家造成严重干扰,甚至导致死亡,因此被认为是严重的全球健康威胁。显然,为了有效地控制白色念珠菌的传播,开发高效的消毒液是一项重要的策略。本研究从膜流动性、膜完整性、蛋白渗漏、细胞及线粒体功能改变等方面探讨了ODB对白色念珠菌的杀真菌机制。ODB可影响白色念珠菌细胞膜的流动性和完整性,导致大量离子、蛋白质、甘油、活性氧、ATP和DNA泄漏,使细胞产生ATP或利用ATP的能力下降或线粒体功能紊乱,DNA含量降低。而这些结构和功能的改变是导致白色念珠菌最终死亡的主要原因。
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引用次数: 0
Information-Based Similarity of Binary Symbol Sequence as a New Index for Sleep Apnea Research 基于信息的二值符号序列相似度作为睡眠呼吸暂停研究的新指标
Shan Wu, Guanzheng Liu
Sleep apnea (SA) as abreathing disorder during sleep, has an increasing incidence in recent years. As a non-invasive method, heart rate variability (HRV) analysis can be effectively used in sleep apnea research. The information-based similarity of binary symbol sequence (BS_IBS) is a symbolic dynamics analysis method, which can be employed to perform nonlinear HRV analysis of sleep apnea patients. In the study, 60 electrocardiogram recordings were used for analysis, and multiple indices in time domain, frequency domain, and nonlinearity were calculated at the same. The similarity between adjacent RR segments was evaluated by calculating the BS_IBS value of them. Our research shows that BS_IBS is a useful sleep apnea screening method and can improve the effect of sleep apnea screening with traditional time-frequency domain indices (the accuracy is increased from 81.7% to 86.7%). This study proves that nonlinear information-based similarity assessment can be used in sleep apnea research and further expands the nonlinear HRV analysis method of sleep apnea.
睡眠呼吸暂停(SA)是一种睡眠过程中的呼吸障碍,近年来发病率越来越高。心率变异性(HRV)分析作为一种无创方法,可以有效地用于睡眠呼吸暂停研究。基于信息的二元符号序列相似度(BS_IBS)是一种符号动力学分析方法,可用于对睡眠呼吸暂停患者进行非线性HRV分析。本研究采用60份心电图记录进行分析,同时计算时域、频域、非线性等多个指标。通过计算相邻RR段的BS_IBS值来评价它们之间的相似性。我们的研究表明,BS_IBS是一种有用的睡眠呼吸暂停筛查方法,可以提高传统时频域指标筛查睡眠呼吸暂停的效果(准确率从81.7%提高到86.7%)。本研究证明了基于非线性信息的相似度评估可用于睡眠呼吸暂停研究,进一步拓展了睡眠呼吸暂停的非线性HRV分析方法。
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引用次数: 0
L1/2 Regularization-Based Deep Incremental Non-negative Matrix Factorization for Tumor Recognition 基于L1/2正则化的深度增量非负矩阵分解肿瘤识别
Lulu Yan, Xiaohui Yang
Non-negative matrix factorization (NMF) is an effective technique for feature representation learning and dimensionality reduction. However, there are two critical challenges for improving the performance of NMF-based methods. One is the sparsity of representation, the other is the sensitivity to the initial value of the iteration, which seriously affects the performance of NMF. To solve the problems, L1/2 regularization is skillfully selected to characterize the sparsity of the data. Furthermore, a layer-wise pre-training strategy in deep learning is used to alleviate the effect of the initial value on NMF, whereby complex network structure is avoided. As such, a L1/2 regularization-based deep NMF (L1/2-DNMF) model is proposed in this study, such that a more stable and sparse deep representation is obtained. Moreover, incremental learning is introduced to reduce the high computational complexity of L1/2-DNMF model, called L1/2-DINMF model, which is suitable for online processing. Experiment results on genetic data-based tumor recognition verify that the proposed L1/2-DINMF model outperforms the classic and state-of-the-art methods.
非负矩阵分解(NMF)是一种有效的特征表示学习和降维技术。然而,提高基于nmf的方法的性能存在两个关键挑战。一个是表示的稀疏性,另一个是对迭代初值的敏感性,这严重影响了NMF的性能。为了解决这些问题,我们巧妙地选择了L1/2正则化来表征数据的稀疏性。此外,采用深度学习中的分层预训练策略减轻了初始值对NMF的影响,从而避免了复杂的网络结构。因此,本研究提出了一种基于L1/2正则化的深度NMF (L1/2- dnmf)模型,从而获得更加稳定和稀疏的深度表示。此外,为了降低L1/2-DNMF模型较高的计算复杂度,引入了增量学习,称为L1/2-DINMF模型,适合在线处理。基于遗传数据的肿瘤识别实验结果验证了所提出的L1/2-DINMF模型优于经典和最先进的方法。
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引用次数: 0
Computation Prediction of the Therapeutic Effect of Metal Stent Implantation for Coronary Bifurcation 金属支架植入术治疗冠状动脉分叉疗效的计算与预测
Xiaotong Yan, Kai Yue, Xinxin Zhang
A good understanding of the characteristics behavior of blood flow is significant for exploring the formation mechanism and process of atherosclerosis (AS), grasping the pathogenesis of AS, and providing effective theoretical guidance for clinical treatment of AS. To predict the influence of plaque on hemodynamics and the therapeutic effect of stent interventional treatment on stenosis artery, the coronary bifurcation models with/without stenosis and with stent implantation were constructed to analyze the hemodynamic characteristics in three cases using fluid-solid interaction method based on COMSOL software. The dynamic velocity, streamline, pressure, Von Mises stress, and displacement distributions in the coronary artery were obtained in these studies. Results show that the velocity of the plaque increased sharply, and the peripheral tissues of the plaque are more prone to the risk of injury because of the higher stress. The blood flow velocity tends to be stable in the stented artery and the velocity distribution is uniform, indicating that the blood supply of branch vessels is further improved, which is conducive to the normal blood supply and stable blood flow.
了解血流特征行为,对于探索动脉粥样硬化(AS)的形成机制和过程,掌握AS的发病机制,为临床治疗提供有效的理论指导具有重要意义。为预测斑块对血流动力学的影响及支架介入治疗狭窄动脉的治疗效果,基于COMSOL软件,构建有狭窄、无狭窄和有支架的冠状动脉分叉模型,采用流固相互作用法分析3例患者血流动力学特征。在这些研究中获得了冠状动脉的动态速度、流线、压力、Von Mises应力和位移分布。结果表明,斑块的速度急剧增加,斑块的周围组织因较高的应激而更容易发生损伤的风险。支架动脉内血流速度趋于稳定,流速分布均匀,说明支血管的血供进一步改善,有利于正常血供和血流稳定。
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引用次数: 0
Effects of Grazing Intensity on Soil Bacterial Community Structure of Stipa grandis Grasslands in Inner Mongolia, China 放牧强度对内蒙古大针茅草地土壤细菌群落结构的影响
Zijie Wang, Yanlin Sun, Xiaoya Chi, Soon-Seong Hong
Grassland ecosystem is one of the indispensable ecosystem types in the world, accounting for approximately 30% of global land area. However, due to overgrazing and other human activities, grassland ecosystem is increasingly seriously degraded. Soil microorganism, as an important component of grassland soil ecology, plays a key role in litter decomposition, material metabolism and circulation. According to the results of large previous literature, soil microbial community structure could be affected by vegetation characteristics, soil properties and other environmental factors. Not surprisingly, soil microbial community structure could also be affected by different soil management strategies, including grazing intensity. As grazing could directly affect plant growth, soil porosity, nitrogen circulation and soil microbial community characteristics, the soil microbial community could be not only directly affected by grazing intensity, but also indirectly affected by the vegetation characteristics and soil properties that had changed with difference in grazing intensity. Therefore, there has been no unified conclusion about the effect of grazing intensity on soil microbial community. To further clarify this question, we utilized 16S amplifiers absolute quantitative sequencing technology to analyze the absolute abundance, diversity and composition of soil bacterial communities of Stipa grandis grasslands under different grazing intensity in Xilingol League, Inner Mongolia, China in this study. The correlations with soil bacterial communities and their corresponding environmental factors were also analyzed. Our results suggested that soil bacterial diversity decreased at first and then increased with the increase of grazing intensity, and the evenness had no significant variation with the difference in grazing intensity. Grazing intensity significantly affected the composition of soil bacterial communities at the phylum level: with the increase of grazing intensity, the abundance of Verrucomicrobia decreased at first and then increased, the abundance of Planctomycetes and Gemmatimonadetes significantly decreased, and the abundance of Nitrospirae significantly increased. According to the redundancy analysis with vegetation characteristics and soil properties, it indicated that the dominant soil bacterial phyla showed significant correlations with soil pH value, number of Gramineous species, aboveground biomass of Gramineous species, total aboveground biomass, soil organic matter content, available nitrogen content, available phosphorus and total nitrogen contents. This work could provide more scientific evidence for understanding of the effects of grazing intensity on soil bacterial community structure.
草原生态系统是世界上不可缺少的生态系统类型之一,约占全球陆地面积的30%。然而,由于过度放牧等人类活动,草地生态系统退化日益严重。土壤微生物是草地土壤生态的重要组成部分,在凋落物分解、物质代谢和循环中起着关键作用。根据大量文献研究结果,土壤微生物群落结构会受到植被特征、土壤性质等环境因素的影响。毫不奇怪,不同的土壤管理策略(包括放牧强度)也会影响土壤微生物群落结构。放牧会直接影响植物生长、土壤孔隙度、氮循环和土壤微生物群落特征,因此放牧强度不仅会直接影响土壤微生物群落,还会间接影响随放牧强度变化的植被特征和土壤性质。因此,放牧强度对土壤微生物群落的影响尚无统一的结论。为了进一步阐明这一问题,本研究利用16S扩增绝对定量测序技术,分析了内蒙古锡林郭勒盟不同放牧强度下大针茅草原土壤细菌群落的绝对丰度、多样性和组成。并分析了其与土壤细菌群落及其环境因子的相关性。结果表明,随着放牧强度的增加,土壤细菌多样性呈先降低后增加的趋势,均匀度随放牧强度的不同无显著变化。放牧强度在门水平上显著影响土壤细菌群落的组成:随着放牧强度的增加,Verrucomicrobia的丰度先降低后升高,plantomycetes和Gemmatimonadetes的丰度显著降低,Nitrospirae的丰度显著升高。通过与植被特征和土壤特性的冗余分析,表明优势土壤细菌门与土壤pH值、禾本科种数、禾本科种地上生物量、地上总生物量、土壤有机质含量、有效氮含量、有效磷含量和全氮含量呈显著相关。本研究可为了解放牧强度对土壤细菌群落结构的影响提供更多科学依据。
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引用次数: 1
Use Chou's 5-steps Rule to Study the Mechanism of Uncaria Rhynchophylla for Treating Alzheimer's Disease Based on Network Pharmacology 基于网络药理学的周氏五步法研究钩藤治疗阿尔茨海默病的作用机制
Meng Fang, Peng Zeng, Jinglou Chen, Han Zhao, Haiping Wang, Jing Guo
Objective: To tentatively investigate the mechanism of uncaria rhynchophylla (UR) in treatment of Alzheimer's disease (AD). Methods: The targets and pathways of UR against AD were obtained from network pharmacology analysis. Results: We analyzed and obtained 7 active ingredients of UR, 29 targets of UR for treatment of AD, of which 26.9% targets were protein-modifying enzymes. The core active ingredients of UR were C3, C6, C7 and C5. The core targets of UR in the treatment of AD are AKT1, CASP3 and MTOR. The enrichment analysis of GO biological process suggests that the biological function of UR in the treatment of AD mainly involves regulation of neurotransmitter levels, rhythmic process, cellular response to nitrogen compound, calcium ion transport, response to toxic substance, response to oxygen levels, maintenance of location, positive regulation of cell death, and apoptotic signaling pathway, etc. KEGG pathway enrichment analysis showed that the most significant enrichment signaling pathways were neuroactive ligand-receptor interaction, calcium signaling pathway, cAMP signaling pathway, PI3K-Akt signaling pathway and so on. Conclusion: UR against AD may be related to its multiple components, multiple targets and biological functions. This study can provide a theoretical basis for further experimental and clinical research.
目的:初步探讨钩尾虫(uncaria rhynchophyla, UR)治疗阿尔茨海默病(Alzheimer's disease, AD)的作用机制。方法:通过网络药理学分析获得UR抗AD的靶点和通路。结果:我们分析得到了UR的7种有效成分,获得了UR治疗AD的靶点29个,其中26.9%的靶点为蛋白修饰酶。UR的核心活性成分为C3、C6、C7和C5。UR治疗AD的核心靶点是AKT1、CASP3和MTOR。氧化石墨烯生物过程富集分析提示,尿酸治疗AD的生物学功能主要包括调节神经递质水平、节律过程、细胞对氮化合物的反应、钙离子转运、对有毒物质的反应、对氧水平的反应、位置维持、对细胞死亡的正向调节、凋亡信号通路等。KEGG通路富集分析显示,富集最显著的信号通路为神经活性配体-受体相互作用、钙信号通路、cAMP信号通路、PI3K-Akt信号通路等。结论:UR抗AD可能与其多组分、多靶点及生物学功能有关。本研究可为进一步的实验和临床研究提供理论依据。
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引用次数: 0
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The Fifth International Conference on Biological Information and Biomedical Engineering
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