Reverse fingerprinting, similarity searching by group fusion and fingerprint bit importance

Summary Recent research has shown that using data fusion rules in fingerprint-based similarity searching can improve results over traditional searches. Group fusion scores, which use multiple reference compounds, have in particular been shown to be quite effective in increasing enrichment rates over single reference structure based searches. In this paper, the effectiveness of using data fusion with multiple reference compounds to increase similarity search recall rates was investigated using 44 biological targets and four different 2D fingerprinting systems, including a new 2D typed triangle fingerprinting system introduced here. Scaffold-hopping abilities using data fusion rules were investigated using eight (8) different classes of scaffolds active against cGMP phosphodiesterase isoform 5 (PDE5). An approach to using the reference group for ranking and visualizing important fingerprints bits, or reverse fingerprinting, was presented, and used to score and visualize important pharmacophore features within sample active molecules. Finally, similarity statistics within the reference groups were investigated and compared to recall rates.     

Symmetries and Exact Solutions of the Breaking Soliton Equation

With the aid of the classical Lie group method and nonclassical Lie group method, we derive the classical Lie point symmetry and the nonclassical Lie point symmetry of (2+1)-dimensional breaking soliton (BS) equation. Using the symmetries, we find six classical similarity reductions and two nonclassical similarity reductions of the BS equation. Varieties of exact solutions of the BS equation are obtained by solving the reduced equations.     

A weight’s agglomerative method for detecting communities in weighted networks based on weight’s similarity

This paper proposes the new definition of the community structure of the weighted networks that groups of nodes in which the edge's weights distribute uniformly but at random between them. It can describe the steady connections between nodes or some similarity between nodes' functions effectively. In order to detect the community structure efficiently, a threshold coefficient κ to evaluate the equivalence of edges' weights and a new weighted modularity based on the weight's similarity are proposed. Then, constructing the weighted matrix and using the agglomerative mechanism, it presents a weight's agglomerative method based on optimizing the modularity to detect communities. For a network with n nodes, the algorithm can detect the community structure in time O(n²log₂ⁿ). Simulations on networks show that the algorithm has higher accuracy and precision than the existing techniques. Furthermore, with the change of κ the algorithm discovers a special hierarchical organization which can describe the various steady connections between nodes in groups.     

基于DCGANs的半片光伏组件电致发光图像增强技术

针对半片光伏组件电致发光（electroluminescence,EL）缺陷自动识别过程中训练用样本不足导致模型过拟合的问题,采用深度卷积生成对抗网络（deep convolutional generative adversarial networks,DCGANs）生成可控制属性的半片光伏组件EL图像,再采用多尺度结构相似性（multiscale structural similarity,MS-SSIM）指标对生成的EL图像与拍摄的EL图像之间的相似程度进行了评估。评估结果得到,使用DCGANs生成的所有类型半片光伏组件的EL图像与拍摄的EL图像的MS-SSIM指标都大于0.55,大部分的MS-SSIM值在0.7附近。在分类模型的训练过程中,测试集准确率随着训练集中生成图像数量的增加而升高,当生成图像数量达到6 000张时,测试集准确率达到97.92%。实验结果表明,采用DCGANs能够生成高质量且可控制属性的半片光伏组件EL图像,较好地解决因缺少训练样本而导致的模型过拟合问题。     

一类非线性相对转动周期系统的平衡稳定性分析

利用一类周期性变系数线性常微分方程解的基本矩阵的Jordan形，分析一类非线性相对转动系统扭转的运动稳定性，从而得到非线性相对转动周期系统的运动稳定准则. 运用Lyapunov函数法，对广泛存在的一类机械传动系统的相对转动运动的平衡稳定位置的稳定域进行研究，并给出数学解析表达式. 这为工程中广泛存在的这类机械传动系统稳定工作区间工作参数的选取和相似模拟提供了理论依据及方法，据此可进一步分析和评价大型复杂旋转机械主传动系统的扭振稳定性. 关键词： 相对转动 相似模拟 运动稳定 平衡稳定     

Determination of Brain Tissue Samples Storage Conditions for Reproducible Intraoperative Lipid Profiling

Ex-vivo molecular profiling has recently emerged as a promising method for intraoperative tissue identification, especially in neurosurgery. The short-term storage of resected samples at room temperature is proposed to have negligible influence on the lipid molecular profiles. However, a detailed investigation of short-term molecular profile stability is required to implement molecular profiling in a clinic. This study evaluates the effect of storage media, temperature, and washing solution to determine conditions that provide stable and reproducible molecular profiles, with the help of ambient ionization mass spectrometry using rat cerebral cortex as model brain tissue samples. Utilizing normal saline for sample storage and washing media shows a positive effect on the reproducibility of the spectra; however, the refrigeration shows a negligible effect on the spectral similarity. Thus, it was demonstrated that up to hour-long storage in normal saline, even at room temperature, ensures the acquisition of representative molecular profiles using ambient ionization mass spectrometry.     

Computational Drug Repurposing Based on a Recommendation System and Drug–Drug Functional Pathway Similarity

Drug repurposing identifies new clinical indications for existing drugs. It can be used to overcome common problems associated with cancers, such as heterogeneity and resistance to established therapies, by rapidly adapting known drugs for new treatment. In this study, we utilized a recommendation system learning model to prioritize candidate cancer drugs. We designed a drug–drug pathway functional similarity by integrating multiple genetic and epigenetic alterations such as gene expression, copy number variation (CNV), and DNA methylation. When compared with other similarities, such as SMILES chemical structures and drug targets based on the protein–protein interaction network, our approach provided better interpretable models capturing drug response mechanisms. Furthermore, our approach can achieve comparable accuracy when evaluated with other learning models based on large public datasets (CCLE and GDSC). A case study about the Erlotinib and OSI-906 (Linsitinib) indicated that they have a synergistic effect to reduce the growth rate of tumors, which is an alternative targeted therapy option for patients. Taken together, our computational method characterized drug response from the viewpoint of a multi-omics pathway and systematically predicted candidate cancer drugs with similar therapeutic effects.     

A study for quality evaluation of Taxilli Herba from different hosts based on fingerprint-activity relationship modeling and multivariate statistical analysis

In this study, a fingerprint-activity relationship modeling between chemical fingerprints and antirheumatic activity was established, and multivariate statistical analysis was used to evaluate the quality of Taxilli Herba (TH) from different hosts. Characteristic fingerprints of 20 batches of TH samples were generated by high-performance liquid chromatography coupled with triple quadrupole-time of flight tandem mass spectrometry (HPLC-Triple TOF-MS/MS), and the similarity analysis was calculated based on thirteen common characteristic peaks by hierarchical clustering analysis (HCA). Subsequently, nine efficacy markers were discovered by combining fingerprints and antirheumatic activity through grey correlation analysis (GCA) and bivariate correlation analysis (BCA). Meanwhile, the content of 5 constituents in 9 markers was determined by high-performance liquid chromatography coupled with triple quadrupole-linear ion trap tandem mass spectrometry (HPLC-QTRAP-MS/MS). The comprehensive quality of TH was assessed using multivariate statistical analysis, including principal components analysis (PCA) and technique for order preference by similarity to ideal solution (TOPSIS). The results showed that a high dose of TH extract could markedly ameliorate arthritis damage compared to other doses, with flavonoids playing an important role in the antirheumatic activity. The comprehensive quality of samples from Morus alba L. (SS) was superior to those from Liquidambar formosana Hance (FXS). The present study will demonstrate the markers associated with efficacy, and provide an applicable strategy for more comprehensive quality control and evaluation of TH.