GraphCpG: imputation of single-cell methylomes based on locus-aware neighboring subgraphs.

MOTIVATION: Single-cell DNA methylation sequencing can assay DNA methylation at single-cell resolution. However, incomplete coverage compromises related downstream analyses, outlining the importance of imputation techniques. With a rising number of cell samples in recent large datasets, scalable and efficient imputation models are critical to addressing the sparsity for genome-wide analyses. RESULTS: We proposed a novel graph-based deep learning approach to impute methylation matrices based on locus-aware neighboring subgraphs with locus-aware encoding orienting on one cell type. Merely using the CpGs methylation matrix, the obtained GraphCpG outperforms previous methods on datasets containing more than hundreds of cells and achieves competitive performance on smaller datasets, with subgraphs of predicted sites visualized by retrievable bipartite graphs. Besides better imputation performance with increasing cell number, it significantly reduces computation time and demonstrates improvement in downstream analysis. AVAILABILITY AND IMPLEMENTATION: The source code is freely available at https://github.com/yuzhong-deng/graphcpg.git.

High-Precision Wafer Bonding Alignment Mark Using Moiré Fringes and Digital Grating.

This paper investigates a moiré-based mark for high-precision wafer bonding alignment. During alignment, the mark is combined with digital grating, which has the benefits of high precision and small size. A digital grating is superimposed on the mark to generate moiré fringes. By performing a phase calculation on the moiré fringe images corresponding to the upper and lower wafers, the relative offset of the upper and lower wafers can be accurately calculated. These moiré fringes are exceptionally stable, thereby enhancing the alignment stability. In this study, through practical experiments, we tested the rationality and practicability of the mark.

scMelody: An Enhanced Consensus-Based Clustering Model for Single-Cell Methylation Data by Reconstructing Cell-to-Cell Similarity.

Single-cell DNA methylation sequencing technology has brought new perspectives to investigate epigenetic heterogeneity, supporting a need for computational methods to cluster cells based on single-cell methylation profiles. Although several methods have been developed, most of them cluster cells based on single (dis)similarity measures, failing to capture complete cell heterogeneity and resulting in locally optimal solutions. Here, we present scMelody, which utilizes an enhanced consensus-based clustering model to reconstruct cell-to-cell methylation similarity patterns and identifies cell subpopulations with the leveraged information from multiple basic similarity measures. Besides, benefitted from the reconstructed cell-to-cell similarity measure, scMelody could conveniently leverage the clustering validation criteria to determine the optimal number of clusters. Assessments on distinct real datasets showed that scMelody accurately recapitulated methylation subpopulations and outperformed existing methods in terms of both cluster partitions and the number of clusters. Moreover, when benchmarking the clustering stability of scMelody on a variety of synthetic datasets, it achieved significant clustering performance gains over existing methods and robustly maintained its clustering accuracy over a wide range of number of cells, number of clusters and CpG dropout proportions. Finally, the real case studies demonstrated the capability of scMelody to assess known cell types and uncover novel cell clusters.

CaMelia: imputation in single-cell methylomes based on local similarities between cells.

MOTIVATION: Single-cell DNA methylation sequencing detects methylation levels with single-cell resolution, while this technology is upgrading our understanding of the regulation of gene expression through epigenetic modifications. Meanwhile, almost all current technologies suffer from the inherent problem of detecting low coverage of the number of CpGs. Therefore, addressing the inherent sparsity of raw data is essential for quantitative analysis of the whole genome. RESULTS: Here, we reported CaMelia, a CatBoost gradient boosting method for predicting the missing methylation states based on the locally paired similarity of intercellular methylation patterns. On real single-cell methylation datasets, CaMelia yielded significant imputation performance gains over previous methods. Furthermore, applying the imputed data to the downstream analysis of cell-type identification, we found that CaMelia helped to discover more intercellular differentially methylated loci that were masked by the sparsity in raw data, and the clustering results demonstrated that CaMelia could preserve cell-cell relationships and improve the identification of cell types and cell subpopulations. AVAILABILITY AND IMPLEMENTATION: Python code is available at https://github.com/JxTang-bioinformatics/CaMelia. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Bayesian Estimation of Human Impedance and Motion Intention for Human-Robot Collaboration.

This article proposes a Bayesian method to acquire the estimation of human impedance and motion intention in a human-robot collaborative task. Combining with the prior knowledge of human stiffness, estimated stiffness obeying Gaussian distribution is obtained by Bayesian estimation, and human motion intention can be also estimated. An adaptive impedance control strategy is employed to track a target impedance model and neural networks are used to compensate for uncertainties in robotic dynamics. Comparative simulation results are carried out to verify the effectiveness of estimation method and emphasize the advantages of the proposed control strategy. The experiment, performed on Baxter robot platform, illustrates a good system performance.

Adaptive boundary control of a vibrating cantilever nanobeam considering small scale effects.

This paper presents vibration control analysis for a cantilever nanobeam system. The dynamics of the system is obtained by the non-local elastic relationship which characterizes the small scale effects. The boundary conditions and governing equation are respectively expressed by several ordinary differential equations (ODE) and a partial differential equation (PDE) with the help of the Hamilton's principle. Model-based control and adaptive control are both designed at the free end to regulate the vibration in the control section. By employing the Lyapunov stability approach, the system state can be proven to be substantiated to converge to zero's small neighbourhood with appropriate parameters. Simulation results illustrate that the designed control is feasible for the nanobeam system.

PretiMeth: precise prediction models for DNA methylation based on single methylation mark.

BACKGROUND: The computational prediction of methylation levels at single CpG resolution is promising to explore the methylation levels of CpGs uncovered by existing array techniques, especially for the 450 K beadchip array data with huge reserves. General prediction models concentrate on improving the overall prediction accuracy for the bulk of CpG loci while neglecting whether each locus is precisely predicted. This leads to the limited application of the prediction results, especially when performing downstream analysis with high precision requirements. RESULTS: Here we reported PretiMeth, a method for constructing precise prediction models for each single CpG locus. PretiMeth used a logistic regression algorithm to build a prediction model for each interested locus. Only one DNA methylation feature that shared the most similar methylation pattern with the CpG locus to be predicted was applied in the model. We found that PretiMeth outperformed other algorithms in the prediction accuracy, and kept robust across platforms and cell types. Furthermore, PretiMeth was applied to The Cancer Genome Atlas data (TCGA), the intensive analysis based on precise prediction results showed that several CpG loci and genes (differentially methylated between the tumor and normal samples) were worthy for further biological validation. CONCLUSION: The precise prediction of single CpG locus is important for both methylation array data expansion and downstream analysis of prediction results. PretiMeth achieved precise modeling for each CpG locus by using only one significant feature, which also suggested that our precise prediction models could be probably used for reference in the probe set design when the DNA methylation beadchip update. PretiMeth is provided as an open source tool via https://github.com/JxTang-bioinformatics/PretiMeth.

A Hybrid Ensemble Approach for Identifying Robust Differentially Methylated Loci in Pan-Cancers.

DNA methylation is a widely investigated epigenetic mark that plays a vital role in tumorigenesis. Advancements in high-throughput assays, such as the Infinium 450K platform, provide genome-scale DNA methylation landscapes in single-CpG locus resolution, and the identification of differentially methylated loci has become an insightful approach to deepen our understanding of cancers. However, the situation with extremely unbalanced numbers of samples and loci (approximately 1:1,000) makes it rather difficult to explore differential methylation between the sick and the normal. In this article, a hybrid approach based on ensemble feature selection for identifying differentially methylated loci (HyDML) was proposed by incorporating instance perturbation and multiple function models. Experiments on data from The Cancer Genome Atlas showed that HyDML not only achieved effective DML identification, but also outperformed the single-feature selection approach in terms of classification performance and the robustness of feature selection. The intensive analysis of the DML indicated that different types of cancers have mutual patterns, and the stable DML sharing in pan-cancers is of the great potential to be biomarkers, which may strengthen the confidence of domain experts to implement biological validations.

MRCNN: a deep learning model for regression of genome-wide DNA methylation.

BACKGROUND: Determination of genome-wide DNA methylation is significant for both basic research and drug development. As a key epigenetic modification, this biochemical process can modulate gene expression to influence the cell differentiation which can possibly lead to cancer. Due to the involuted biochemical mechanism of DNA methylation, obtaining a precise prediction is a considerably tough challenge. Existing approaches have yielded good predictions, but the methods either need to combine plenty of features and prerequisites or deal with only hypermethylation and hypomethylation. RESULTS: In this paper, we propose a deep learning method for prediction of the genome-wide DNA methylation, in which the Methylation Regression is implemented by Convolutional Neural Networks (MRCNN). Through minimizing the continuous loss function, experiments show that our model is convergent and more precise than the state-of-art method (DeepCpG) according to results of the evaluation. MRCNN also achieves the discovery of de novo motifs by analysis of features from the training process. CONCLUSIONS: Genome-wide DNA methylation could be evaluated based on the corresponding local DNA sequences of target CpG loci. With the autonomous learning pattern of deep learning, MRCNN enables accurate predictions of genome-wide DNA methylation status without predefined features and discovers some de novo methylation-related motifs that match known motifs by extracting sequence patterns.