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Single-cell RNA sequencing (scRNA-seq) is currently an important technology for identifying cell types and studying diseases at the genetic level. Identifying rare cell types is biologically important as one of the downstream data analyses of single-cell RNA sequencing. Although rare cell identification methods have been developed, most of these suffer from insufficient mining of intercellular similarities, low scalability, and being time-consuming. In this paper, we propose a single-cell similarity division algorithm (scSID) for identifying rare cells. It takes cell-to-cell similarity into consideration by analyzing both inter-cluster and intra-cluster similarities, and discovers rare cell types based on the similarity differences. We show that scSID outperforms other existing methods by benchmarking it on different experimental datasets. Application of scSID to multiple datasets, including 68K PBMC and intestine, highlights its exceptional scalability and remarkable ability to identify rare cell populations.

Chromosome karyotyping is an important yet labor-intensive procedure for diagnosing genetic diseases. Automating such a procedure drastically reduces the manual work of cytologists and increases congenital disease diagnosing precision. Researchers have contributed to chromosome segmentation and classification for decades. However, very few studies integrate the two tasks as a unified, fully automatic procedure or achieved a promising performance. This paper addresses the gap by presenting: 1) A novel chromosome segmentation module named ChrRender, with the idea of rendering the chromosome instances by combining rich global features from the backbone and coarse mask prediction from Mask R-CNN; 2) A devised chromosome classification module named ChrNet4 that pays more attention to channel-wise dependencies from aggregated informative features and calibrating the channel interdependence; 3) An integrated Render-Attention-Architecture to accomplish fully automatic karyotyping with segmentation and classification modules; 4) A strategy for eliminating differences between training data and segmentation output data to be classified. These proposed methods are implemented in three ways on the public Q-band BioImLab dataset and a G-band private dataset. The results indicate promising performance: 1) on the joint karyotyping task, which predicts a karyotype image by first segmenting an original microscopical image, then classifying each segmentation output with a precision of 89.75% and 94.22% on the BioImLab and private dataset, respectively; 2) On the separate task with two datasets, ChrRender obtained AP50 of 96.652% and 96.809% for segmentation, ChrNet4 achieved 95.24% and 94.07% for classification, respectively. The COCO format annotation files of BioImLab used in this paper are available at https://github.com/Alex17swim/BioImLab The study introduces an integrated workflow to predict a karyotyping image from a Microscopical Chromosome Image. With state-of-the-art performance on a public dataset, the proposed Render-Attention-Architecture has accomplished fully automatic chromosome karyotyping.

As the most pervasive epigenetic marker present on mRNAs and long non-coding RNAs (lncRNAs), N6-methyladenosine (m6A) RNA methylation has been shown to participate in essential biological processes. Recent studies have revealed the distinct patterns of m6A methylome across human tissues, and a major challenge remains in elucidating the tissue-specific presence and circuitry of m6A methylation. We present here a comprehensive online platform, m6A-TSHub, for unveiling the context-specific m6A methylation and genetic mutations that potentially regulate m6A epigenetic mark. m6A-TSHub consists of four core components, including (1) m6A-TSDB, a comprehensive database of 184,554 functionally annotated m6A sites derived from 23 human tissues and 499,369 m6A sites from 25 tumor conditions, respectively; (2) m6A-TSFinder, a web server for high-accuracy prediction of m6A methylation sites within a specific tissue from RNA sequences, which was constructed using multi-instance deep neural networks with gated attention; (3) m6A-TSVar, a web server for assessing the impact of genetic variants on tissue-specific m6A RNA modifications; and (4) m6A-CAVar, a database of 587,983 The Cancer Genome Atlas (TCGA) cancer mutations (derived from 27 cancer types) that were predicted to affect m6A modifications in the primary tissue of cancers. The database should make a useful resource for studying the m6A methylome and the genetic factors of epitranscriptome disturbance in a specific tissue (or cancer type). m6A-TSHub is accessible at www.xjtlu.edu.cn/biologicalsciences/m6ats.

Colocalization analysis of genomic region sets has been widely adopted to unveil potential functional interactions between corresponding biological attributes, which often serves as the basis for further investigation. A number of methods have been developed for colocalization analysis of genomic elements. However, none of them explicitly considered the transcriptome heterogeneity and isoform ambiguity, making them less appropriate for analyzing transcriptome elements. Here, we developed RgnTX, an R/Bioconductor tool for the colocalization analysis of transcriptome elements with permutation tests. Different from existing approaches, RgnTX directly takes advantage of transcriptome annotation, and offers high flexibility in the null model to simulate realistic transcriptome-wide background, such as the complex alternative splicing patterns. Importantly, it supports the testing of transcriptome elements without clear isoform association, which is often the real scenario due to technical limitations. Proposed package offers a wide selection of pre-defined functions, easy to be utilized by users for visualizing permutation results, calculating shifted z-scores and conducting multiple hypothesis testing under Benjamini-Hochberg correction. Moreover, with synthetic and real datasets, we show that RgnTX novel testing modes return distinct and more significant results compared to existing genome-based methods. We believe RgnTX should make a useful tool to characterize the randomness of the transcriptome, and for conducting statistical association analysis for genomic region sets within the heterogeneous transcriptome. The package now has been accepted by Bioconductor and is freely available at: https://bioconductor.org/packages/RgnTX.

RNA modifications appear to play a role in determining RNA structure and function. Here, the authors develop a deep learning model that predicts the location of 12 RNA modifications using primary sequence, and show that several modifications are associated, which suggests dependencies between them.

The social interaction is one of the necessary skills for social robots to better integrate into human society. However, current social robots interact mainly through audio and visual means with little reliance on haptic interaction. There still exist many obstacles for social robots to interact through touch: 1) the complex manufacturing process of the tactile sensor array is the main obstacle to lowering the cost of production; 2) the haptic interaction mode is complex and diverse. There are no social robot interaction standards and data sets for tactile interactive behavior in the public domain. In view of this, our research looks into the following aspects of tactile perception system: 1) Development of low-cost tactile sensor array, including sensor principle, simulation, manufacture, front-end electronics, examination, then applied to the social robot’s whole body; 2) Establishment of the tactile interactive model and an event-triggered perception model in a social interactive application for the social robot, then design preprocessing and classification algorithm. In this research, we use k-nearest neighbors, tree, support vector machine and other classification algorithms to classify touch behaviors into six different classes. In particular, the cosine k-nearest neighbors and quadratic support vector machine achieve an overall mean accuracy rate of more than 68%, with an individual accuracy rate of more than 80%. In short, our research provides new directions in achieving low-cost intelligent touch interaction for social robots in a real environment. The low-cost tactile sensor array solution and interactive models are expected to be applied to social robots on a large scale.

Post-transcriptional RNA modification occurs on all types of RNA and plays a vital role in regulating every aspect of RNA function. Thanks to the development of high-throughput sequencing technologies, transcriptome-wide profiling of RNA modifications has been made possible. With the accumulation of a large number of high-throughput datasets, bioinformatics approaches have become increasing critical for unraveling the epitranscriptome. We review here the recent progress in bioinformatics approaches for deciphering the epitranscriptomes, including epitranscriptome data analysis techniques, RNA modification databases, disease-association inference, general functional annotation, and studies on RNA modification site prediction. We also discuss the limitations of existing approaches and offer some future perspectives.

Human chromosome classification is essential to the clinical diagnosis of cytogenetical diseases such as genetic disorders and cancer. This process, however, is time-consuming and requires specialist knowledge. Considerable efforts have been made to automat the process. Recently, methods based on Convolutional Neural Networks achieved state-of-the-art results on the chromosome classification task. Many studies used karyotype images in performance evaluation, few studies have reported the results of human chromosome classification on microscopical images. This paper proposes a novel method to classify single chromosome images into one of 24 types. In the proposed method an extended ResNet was first devised to extract features of single chromosome images. A label feature vector was then extracted for each of 24 chromosome types based on a validation dataset. Hausdorff distance between feature vector of an input image and each of 24 label feature vectors were calculated, and the label feature vector that has minimum hausdorff distance to the feature vector of the input image was selected as the potential label of the input image. To finally allocate the single chromosomes from a same microscopical image into one of 24 types, a Label Redistribution strategy was used to shrink the label space and to increase the efficiency of chromosome classification. Experiments were implemented with 90,624 single chromosome images, 644 of which were randomly picked to form a testing set in advance. The classification accuracy on microscopical images using our proposed method achieved an accuracy of 94.72%.

Abstract Background Over one hundred different types of post-transcriptional RNA modifications have been identified in human. Researchers discovered that RNA modifications can regulate various biological processes, and RNA methylation, especially N6-methyladenosine, has become one of the most researched topics in epigenetics. Results To date, the study of epitranscriptome layer gene regulation is mostly focused on the function of mediator proteins of RNA methylation, i.e., the readers, writers and erasers. There is limited investigation of the functional relevance of individual m6A RNA methylation site. To address this, we annotated human m6A sites in large-scale based on the guilt-by-association principle from an RNA co-methylation network. It is constructed based on public human MeRIP-Seq datasets profiling the m6A epitranscriptome under 32 independent experimental conditions. By systematically examining the network characteristics obtained from the RNA methylation profiles, a total of 339,158 putative gene ontology functions associated with 1446 human m6A sites were identified. These are biological functions that may be regulated at epitranscriptome layer via reversible m6A RNA methylation. The results were further validated on a soft benchmark by comparing to a random predictor. Conclusions An online web server m6Acomet was constructed to support direct query for the predicted biological functions of m6A sites as well as the sites exhibiting co-methylated patterns at the epitranscriptome layer. The m6Acomet web server is freely available at: www.xjtlu.edu.cn/biologicalsciences/m6acomet.

With the rapid development of robotic and AI technology in recent years, human–robot interaction has made great advancement, making practical social impact. Verbal commands are one of the most direct and frequently used means for human–robot interaction. Currently, such technology can enable robots to execute pre-defined tasks based on simple and direct and explicit language instructions, e.g., certain keywords must be used and detected. However, that is not the natural way for human to communicate. In this paper, we propose a novel task-based framework to enable the robot to comprehend human intentions using visual semantics information, such that the robot is able to satisfy human intentions based on natural language instructions (total three types, namely clear, vague, and feeling, are defined and tested). The proposed framework includes a language semantics module to extract the keywords despite the explicitly of the command instruction, a visual object recognition module to identify the objects in front of the robot, and a similarity computation algorithm to infer the intention based on the given task. The task is then translated into the commands for the robot accordingly. Experiments are performed and validated on a humanoid robot with a defined task: to pick the desired item out of multiple objects on the table, and hand over to one desired user out of multiple human participants. The results show that our algorithm can interact with different types of instructions, even with unseen sentence structures.

The discovery of cancer of unknown primary (CUP) is of great significance in designing more effective treatments and improving the diagnostic efficiency in cancer patients. In the study, we develop an appropriate machine learning model for tracing the tissue of origin of CUP with high accuracy after feature engineering and model evaluation. Based on a copy number variation data consisting of 4,566 training cases and 1,262 independent validation cases, an XGBoost classifier is applied to 10 types of cancer. Extremely randomized tree (Extra tree) is used for dimension reduction so that fewer variables replace the original high-dimensional variables. Features with top 300 weights are selected and principal component analysis is applied to eliminate noise. We find that XGBoost classifier achieves the highest overall accuracy of 0.8913 in the 10-fold cross-validation for training samples and 0.7421 on independent validation datasets for predicting tumor tissue of origin. Furthermore, by contrasting various performance indices, such as precision and recall rate, the experimental results show that XGBoost classifier significantly improves the classification performance of various tumors with less prediction error, as compared to other classifiers, such as K-nearest neighbors (KNN), Bayes, support vector machine (SVM), and Adaboost. Our method can infer tissue of origin for the 10 cancer types with acceptable accuracy in both cross-validation and independent validation data. It may be used as an auxiliary diagnostic method to determine the actual clinicopathological status of specific cancer.

RNA N 6 -methyladenosine (m 6 A) has emerged as an important epigenetic modification for its role in regulating the stability, structure, processing, and translation of RNA. Instability of m 6 A homeostasis may result in flaws in stem cell regulation, decrease in fertility, and risk of cancer. To this day, experimental detection and quantification of RNA m 6 A modification are still time-consuming and labor-intensive. There is only a limited number of epitranscriptome samples in existing databases, and a matched RNA methylation profile is not often available for a biological problem of interests. As gene expression data are usually readily available for most biological problems, it could be appealing if we can estimate the RNA methylation status from gene expression data using in silico methods. In this study, we explored the possibility of computational prediction of RNA methylation status from gene expression data using classification and regression methods based on mouse RNA methylation data collected from 73 experimental conditions. Elastic Net-regularized Logistic Regression (ENLR), Support Vector Machine (SVM), and Random Forests (RF) were constructed for classification. Both SVM and RF achieved the best performance with the mean area under the curve (AUC) = 0.84 across samples; SVM had a narrower AUC spread. Gene Site Enrichment Analysis was conducted on those sites selected by ENLR as predictors to access the biological significance of the model. Three functional annotation terms were found statistically significant: phosphoprotein, SRC Homology 3 (SH3) domain, and endoplasmic reticulum. All 3 terms were found to be closely related to m 6 A pathway. For regression analysis, Elastic Net was implemented, which yielded a mean Pearson correlation coefficient = 0.68 and a mean Spearman correlation coefficient = 0.64. Our exploratory study suggested that gene expression data could be used to construct predictors for m 6 A methylation status with adequate accuracy. Our work showed for the first time that RNA methylation status may be predicted from the matched gene expression data. This finding may facilitate RNA modification research in various biological contexts when a matched RNA methylation profile is not available, especially in the very early stage of the study.

Known as the “fifth RNA nucleotide”, pseudouridine (Ψ or psi) is the first-discovered and most abundant RNA modification occurring at the Uridine site, and it plays a prominent role in a number of biological processes. Thousands of Ψ sites have been identified within different biological contexts thanks to the advancement in high-throughput sequencing technology; nevertheless, the transcriptome-wide distribution, biomolecular functions, regulatory mechanisms, and disease relevance of pseudouridylation are largely elusive. We report here a web server—PIANO—for pseudouridine site (Ψ) identification and functional annotation. PIANO was built upon a high-accuracy predictor that takes advantage of both conventional sequence features and 42 additional genomic features. When tested on six independent datasets generated from four independent Ψ-profiling technologies (Ψ-seq, RBS-seq, Pseudo-seq, and CeU-seq) as benchmarks, PIANO achieved an average AUC of 0.955 and 0.838 under the full transcript and mature mRNA models, respectively, marking a substantial improvement in accuracy compared to the existing in silico Ψ-site prediction methods, i.e., PPUS (0.713 and 0.707), iRNA-PseU (0.713 and 0.712), and PseUI (0.634 and 0.652). Besides, PIANO web server systematically annotates the predicted Ψ sites with post-transcriptional regulatory mechanisms (miRNA-targets, RBP-binding regions, and splicing sites) in its prediction report to help the users explore potential machinery of Ψ. Moreover, a concise query interface was also built for 4,303 known Ψ sites, which is currently the largest collection of experimentally validated human Ψ sites. The PIANO website is freely accessible at: http://piano.rnamd.com.

Gaze-following is an effective way for intention understanding in human–robot interaction, which aims to follow the gaze of humans to estimate what object is being observed. Most of the existing methods require people and objects to appear in the same image. Due to the limitation in the view of the camera, these methods are not applicable in practice. To address this problem, we propose a method of gaze following that utilizes a geometric map for better estimation. With the help of the map, this method is competitive for cross-frame estimation. On the basis of this method, we propose a novel gaze-based image caption system, which has been studied for the first time. Our experiments demonstrate that the system follows the gaze and describes objects accurately. We believe that this system is competent for autistic children’s rehabilitation training, pension service robots, and other applications.

Currently, although many successful bioinformatics efforts have been reported in the epitranscriptomics field for N 6 -methyladenosine (m 6 A) site identification, none is focused on the substrate specificity of different m 6 A-related enzymes, ie, the methyltransferases (writers) and demethylases (erasers). In this work, to untangle the target specificity and the regulatory functions of different RNA m 6 A writers (METTL3-METT14 and METTL16) and erasers (ALKBH5 and FTO), we extracted 49 genomic features along with the conventional sequence features and used the machine learning approach of random forest to predict their epitranscriptome substrates. Our method achieved reasonable performance on both the writer target prediction (as high as 0.918) and the eraser target prediction (as high as 0.888) in a 5-fold cross-validation, and results of the gene ontology analysis of their preferential targets further revealed the functional relevance of different RNA methylation writers and erasers.