Neoepitopes are significant therapeutic cancer vaccine candidates, given that tumor neoepitopes induce an immune response to eliminate cancer cells. This immune activation depends on the binding affinity between the antigen peptide and the major histocompatibility complex (MHC). The epitope-MHC binding assay is a technologically difficult, time-consuming, and expensive technique. Therefore, prediction methods for these binding affinities have been developed using computational prediction approaches. However, these predictive models are trained on datasets biased toward viral peptides and some MHC alleles and are limited in their prediction of neoepitopes. In particular, because of the wide variety of MHC class II binding formats, the performance of MHC class II prediction must be improved. Here, we propose a novel deep learning model that consists of multi-task bidirectional long short-term memory (Bi-LSTM) models. Our multi-task model can predict neoepitope-MHC class II bindings from limited training data by sharing MHC class I and II training parameters. We confirm that multi-task learning significantly enhances the prediction performances of cancer antigens. Our model achieves an area under the receiver operating characteristic curve (AUC-ROC) of 82.2%, outperforming existing state-of-the-art single allele neoantigen prediction models while maintaining its strong generalization performance.

BACKGROUND: Complex biological systems are described as a multitude of cell-cell interactions (CCIs). Recent single-cell RNA-sequencing studies focus on CCIs based on ligand-receptor (L-R) gene co-expression but the analytical methods are not appropriate to detect many-to-many CCIs. RESULTS: In this work, we propose scTensor, a novel method for extracting representative triadic relationships (or hypergraphs), which include ligand-expression, receptor-expression, and related L-R pairs. CONCLUSIONS: Through extensive studies with simulated and empirical datasets, we have shown that scTensor can detect some hypergraphs that cannot be detected using conventional CCI detection methods, especially when they include many-to-many relationships. scTensor is implemented as a freely available R/Bioconductor package.

BACKGROUND: In the field of neuroscience, neural modules and circuits that control biological functions have been found throughout entire neural networks. Correlations in neural activity can be used to identify such neural modules. Recent technological advances enable us to measure whole-brain neural activity with single-cell resolution in several species including [Formula: see text]. Because current neural activity data in C. elegans contain many missing data points, it is necessary to merge results from as many animals as possible to obtain more reliable functional modules. RESULTS: In this work, we developed a new time-series clustering method, WormTensor, to identify functional modules using whole-brain activity data from C. elegans. WormTensor uses a distance measure, modified shape-based distance to account for the lags and the mutual inhibition of cell-cell interactions and applies the tensor decomposition algorithm multi-view clustering based on matrix integration using the higher orthogonal iteration of tensors (HOOI) algorithm (MC-MI-HOOI), which can estimate both the weight to account for the reliability of data from each animal and the clusters that are common across animals. CONCLUSION: We applied the method to 24 individual C. elegans and successfully found some known functional modules. Compared with a widely used consensus clustering method to aggregate multiple clustering results, WormTensor showed higher silhouette coefficients. Our simulation also showed that WormTensor is robust to contamination from noisy data. WormTensor is freely available as an R/CRAN package https://cran.r-project.org/web/packages/WormTensor .

MOTIVATION: The analysis of RNA-Seq data from individual differentiating cells enables us to reconstruct the differentiation process and the degree of differentiation (in pseudo-time) of each cell. Such analyses can reveal detailed expression dynamics and functional relationships for differentiation. To further elucidate differentiation processes, more insight into gene regulatory networks is required. The pseudo-time can be regarded as time information and, therefore, single-cell RNA-Seq data are time-course data with high time resolution. Although time-course data are useful for inferring networks, conventional inference algorithms for such data suffer from high time complexity when the number of samples and genes is large. Therefore, a novel algorithm is necessary to infer networks from single-cell RNA-Seq during differentiation. RESULTS: In this study, we developed the novel and efficient algorithm SCODE to infer regulatory networks, based on ordinary differential equations. We applied SCODE to three single-cell RNA-Seq datasets and confirmed that SCODE can reconstruct observed expression dynamics. We evaluated SCODE by comparing its inferred networks with use of a DNaseI-footprint based network. The performance of SCODE was best for two of the datasets and nearly best for the remaining dataset. We also compared the runtimes and showed that the runtimes for SCODE are significantly shorter than for alternatives. Thus, our algorithm provides a promising approach for further single-cell differentiation analyses. AVAILABILITY AND IMPLEMENTATION: The R source code of SCODE is available at https://github.com/hmatsu1226/SCODE. CONTACT: [email protected]. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

BACKGROUND: In genome-wide studies, over-representation analysis (ORA) against a set of genes is an essential step for biological interpretation. Many gene annotation resources and software platforms for ORA have been proposed. Recently, Medical Subject Headings (MeSH) terms, which are annotations of PubMed documents, have been used for ORA. MeSH enables the extraction of broader meaning from the gene lists and is expected to become an exhaustive annotation resource for ORA. However, the existing MeSH ORA software platforms are still not sufficient for several reasons. RESULTS: In this work, we developed an original MeSH ORA framework composed of six types of R packages, including MeSH.db, MeSH.AOR.db, MeSH.PCR.db, the org.MeSH.XXX.db-type packages, MeSHDbi, and meshr. CONCLUSIONS: Using our framework, users can easily conduct MeSH ORA. By utilizing the enriched MeSH terms, related PubMed documents can be retrieved and saved on local machines within this framework.