Briefings in Functional Genomics最新文献

Spiralians represent the least studied superclade of bilaterian animals, despite exhibiting the widest diversity of organisms. Although spiralians include iconic organisms, such as octopus, earthworms and clams, a lot remains to be discovered regarding their phylogeny and biology. Here, we review recent attempts to apply single-cell transcriptomics, a new pioneering technology enabling the classification of cell types and the characterisation of their gene expression profiles, to several spiralian taxa. We discuss the methodological challenges and requirements for applying this approach to marine organisms and explore the insights that can be brought by such studies, both from a biomedical and evolutionary perspective. For instance, we show that single-cell sequencing might help solve the riddle of the homology of larval forms across spiralians, but also to better characterise and compare the processes of regeneration across taxa. We highlight the capacity of single-cell to investigate the origin of evolutionary novelties, as the mollusc shell or the cephalopod visual system, but also to interrogate the conservation of the molecular fingerprint of cell types at long evolutionary distances. We hope that single-cell sequencing will open a new window in understanding the biology of spiralians, and help renew the interest for these overlooked but captivating organisms.

The chromatin loops in the three-dimensional (3D) structure of chromosomes are essential for the regulation of gene expression. Despite the fact that high-throughput chromatin capture techniques can identify the 3D structure of chromosomes, chromatin loop detection utilizing biological experiments is arduous and time-consuming. Therefore, a computational method is required to detect chromatin loops. Deep neural networks can form complex representations of Hi-C data and provide the possibility of processing biological datasets. Therefore, we propose a bagging ensemble one-dimensional convolutional neural network (Be-1DCNN) to detect chromatin loops from genome-wide Hi-C maps. First, to obtain accurate and reliable chromatin loops in genome-wide contact maps, the bagging ensemble learning method is utilized to synthesize the prediction results of multiple 1DCNN models. Second, each 1DCNN model consists of three 1D convolutional layers for extracting high-dimensional features from input samples and one dense layer for producing the prediction results. Finally, the prediction results of Be-1DCNN are compared to those of the existing models. The experimental results indicate that Be-1DCNN predicts high-quality chromatin loops and outperforms the state-of-the-art methods using the same evaluation metrics. The source code of Be-1DCNN is available for free at https://github.com/HaoWuLab-Bioinformatics/Be1DCNN.

Breast cancer is a heterogeneous disease and can be divided into several subtypes with unique prognostic and molecular characteristics. The classification of breast cancer subtypes plays an important role in the precision treatment and prognosis of breast cancer. Benefitting from the relation-aware ability of a graph convolution network (GCN), we present a multi-omics integrative method, the attention-based GCN (AGCN), for breast cancer molecular subtype classification using messenger RNA expression, copy number variation and deoxyribonucleic acid methylation multi-omics data. In the extensive comparative studies, our AGCN models outperform state-of-the-art methods under different experimental conditions and both attention mechanisms and the graph convolution subnetwork play an important role in accurate cancer subtype classification. The layer-wise relevance propagation (LRP) algorithm is used for the interpretation of model decision, which can identify patient-specific important biomarkers that are reported to be related to the occurrence and development of breast cancer. Our results highlighted the effectiveness of the GCN and attention mechanisms in multi-omics integrative analysis and the implement of the LRP algorithm can provide biologically reasonable insights into model decision.

Background: A large number of experiments show that the abnormal expression of miRNA is closely related to the occurrence, diagnosis and treatment of diseases. Identifying associations between miRNAs and diseases is important for clinical applications of complex human diseases. However, traditional biological experimental methods and calculation-based methods have many limitations, which lead to the development of more efficient and accurate deep learning methods for predicting miRNA-disease associations.

Results: In this paper, we propose a novel model on the basis of adaptive deep propagation graph neural network to predict miRNA-disease associations (ADPMDA). We first construct the miRNA-disease heterogeneous graph based on known miRNA-disease pairs, miRNA integrated similarity information, miRNA sequence information and disease similarity information. Then, we project the features of miRNAs and diseases into a low-dimensional space. After that, attention mechanism is utilized to aggregate the local features of central nodes. In particular, an adaptive deep propagation graph neural network is employed to learn the embedding of nodes, which can adaptively adjust the local and global information of nodes. Finally, the multi-layer perceptron is leveraged to score miRNA-disease pairs.

Conclusion: Experiments on human microRNA disease database v3.0 dataset show that ADPMDA achieves the mean AUC value of 94.75% under 5-fold cross-validation. We further conduct case studies on the esophageal neoplasm, lung neoplasms and lymphoma to confirm the effectiveness of our proposed model, and 49, 49, 47 of the top 50 predicted miRNAs associated with these diseases are confirmed, respectively. These results demonstrate the effectiveness and superiority of our model in predicting miRNA-disease associations.

RNA-binding proteins (RBPs) are essential for post-transcriptional gene regulation in eukaryotes, including splicing control, mRNA transport and decay. Thus, accurate identification of RBPs is important to understand gene expression and regulation of cell state. In order to detect RBPs, a number of computational models have been developed. These methods made use of datasets from several eukaryotic species, specifically from mice and humans. Although some models have been tested on Arabidopsis, these techniques fall short of correctly identifying RBPs for other plant species. Therefore, the development of a powerful computational model for identifying plant-specific RBPs is needed. In this study, we presented a novel computational model for locating RBPs in plants. Five deep learning models and ten shallow learning algorithms were utilized for prediction with 20 sequence-derived and 20 evolutionary feature sets. The highest repeated five-fold cross-validation accuracy, 91.24% AU-ROC and 91.91% AU-PRC, was achieved by light gradient boosting machine. While evaluated using an independent dataset, the developed approach achieved 94.00% AU-ROC and 94.50% AU-PRC. The proposed model achieved significantly higher accuracy for predicting plant-specific RBPs as compared to the currently available state-of-art RBP prediction models. Despite the fact that certain models have already been trained and assessed on the model organism Arabidopsis, this is the first comprehensive computer model for the discovery of plant-specific RBPs. The web server RBPLight was also developed, which is publicly accessible at https://iasri-sg.icar.gov.in/rbplight/, for the convenience of researchers to identify RBPs in plants.

Cyclin proteins are a group of proteins that activate the cell cycle by forming complexes with cyclin-dependent kinases. Identifying cyclins correctly can provide key clues to understanding the function of cyclins. However, due to the low similarity between cyclin protein sequences, the advancement of a machine learning-based approach to identify cycles is urgently needed. In this study, cyclin protein sequence features were extracted using the profile-based auto-cross covariance method. Then the features were ranked and selected with maximum relevance-maximum distance (MRMD) 1.0 and MRMD2.0. Finally, the prediction model was assessed through 10-fold cross-validation. The computational experiments showed that the best protein sequence features generated by MRMD1.0 could correctly predict 98.2% of cyclins using the random forest (RF) classifier, whereas seven-dimensional key protein sequence features identified with MRMD2.0 could correctly predict 96.1% of cyclins, which was superior to previous studies on the same dataset both in terms of dimensionality and performance comparisons. Therefore, our work provided a valuable tool for identifying cyclins. The model data can be downloaded from https://github.com/YUshunL/cyclin.

Subcellular localizations of ncRNAs are associated with specific functions. Currently, an increasing number of biological researchers are focusing on computational approaches to identify subcellular localizations of ncRNAs. However, the performance of the existing computational methods is low and needs to be further studied. First, most prediction models are trained with outdated databases. Second, only a few predictors can identify multiple subcellular localizations simultaneously. In this work, we establish three human ncRNA subcellular datasets based on the latest RNALocate, including lncRNA, miRNA and snoRNA, and then we propose a novel multi-label classification model based on ensemble learning called ncRNALocate-EL to identify multi-label subcellular localizations of three ncRNAs. The results show that the ncRNALocate-EL outperforms previous methods. Our method achieved an average precision of 0.709,0.977 and 0.730 on three human ncRNA datasets. The web server of ncRNALocate-EL has been established, which can be accessed at https://bliulab.net/ncRNALocate-EL.

Single-cell RNA-sequencing (scRNA-seq) technologies have enabled the study of human cancers in individual cells, which explores the cellular heterogeneity and the genotypic status of tumors. Gene signature identification plays an important role in the precise classification of cancer subtypes. However, most existing gene selection methods only select the same informative genes for each subtype. In this study, we propose a novel gene selection method, automatic association feature learning (AAFL), which automatically identifies different gene signatures for different cell subpopulations (cancer subtypes) at the same time. The proposed AAFL method combines the residual network with the low-rank network, which selects genes that are most associated with the corresponding cell subpopulations. Moreover, the differential expression genes are acquired before gene selection to filter the redundant genes. We apply the proposed feature learning method to the real cancer scRNA-seq data sets (melanoma) to identify cancer subtypes and detect gene signatures of identified cancer subtypes. The experimental results demonstrate that the proposed method can automatically identify different gene signatures for identified cancer subtypes. Gene ontology enrichment analysis shows that the identified gene signatures of different subtypes reveal the key biological processes and pathways. These gene signatures are expected to bring important implications for understanding cellular heterogeneity and the complex ecosystem of tumors.

Artificial intelligence is revolutionizing all fields that affect people's lives and health. One of the most critical applications is in the study of tumors. It is the case of glioblastoma (GBM) that has behaviors that need to be understood to develop effective therapies. Due to advances in single-cell RNA sequencing (scRNA-seq), it is possible to understand the cellular and molecular heterogeneity in the GBM. Given that there are different cell groups in these tumors, there is a need to apply Machine Learning (ML) algorithms. It will allow extracting information to understand how cancer changes and broaden the search for effective treatments. We proposed multiple comparisons of ML algorithms to classify cell groups based on the GBM scRNA-seq data. This broad comparison spectrum can show the scientific-medical community which models can achieve the best performance in this task. In this work are classified the following cell groups: Tumor Core (TC), Tumor Periphery (TP) and Normal Periphery (NP), in binary and multi-class scenarios. This work presents the biomarker candidates found for the models with the best results. The analyses presented here allow us to verify the biomarker candidates to understand the genetic characteristics of GBM, which may be affected by a suitable identification of GBM heterogeneity. This work obtained for the four scenarios covered cross-validation results of $93.03% pm 5.37%$, $97.42% pm 3.94%$, $98.27% pm 1.81%$ and $93.04% pm 6.88%$ for the classification of TP versus TC, TP versus NP, NP versus TP and TC (TPC) and NP versus TP versus TC, respectively.