Current Issue : October-December Volume : 2022 Issue Number : 4 Articles : 5 Articles
Background: To reduce drug side effects and enhance their therapeutic effect compared with single drugs, drug combination research, combining two or more drugs, is highly important. Conducting in-vivo and in-vitro experiments on a vast number of drug combinations incurs astronomical time and cost. To reduce the number of combinations, researchers classify whether drug combinations are synergistic through in-silico methods. Since unstructured data, such as biomedical documents, include experimental types, methods, and results, it can be beneficial extracting features from documents to predict anti-cancer drug combination synergy. However, few studies predict anti-cancer drug combination synergy using document-extracted features. Results: We present a novel approach for anti-cancer drug combination synergy prediction using document-based feature extraction. Our approach is divided into two steps. First, we extracted documents containing validated anti-cancer drug combinations and cell lines. Drug and cell line synonyms in the extracted documents were converted into representative words, and the documents were preprocessed by tokenization, lemmatization, and stopword removal. Second, the drug and cell line features were extracted from the preprocessed documents, and training data were constructed by feature concatenation. A prediction model based on deep and machine learning was created using the training data. The use of our features yielded higher results compared to the majority of published studies. Conclusions: Using our prediction model, researchers can save time and cost on new anti-cancer drug combination discoveries. Additionally, since our feature extraction method does not require structuring of unstructured data, new data can be immediately applied without any data scalability issues....
Background: Although single-cell RNA sequencing of xenograft samples has been widely used, no comprehensive bioinformatics pipeline is available for human and mouse mixed single-cell analyses. Considering the numerous homologous genes across the human and mouse genomes, misalignment errors should be evaluated, and a new algorithm is required. We assessed the extents and effects of misalignment errors and exonic multi-mapping events when using human and mouse combined reference data and developed a new bioinformatics pipeline with expression-based species deconvolution to minimize errors. We also evaluated false-positive signals presumed to originate from ambient RNA of the other species and address the importance to computationally remove them. Result: Error when using combined reference account for an average of 0.78% of total reads, but such reads were concentrated to few genes that were greatly affected. Human and mouse mixed single-cell data, analyzed using our pipeline, clustered well with unmixed data and showed higher k-nearest-neighbor batch effect test and Local Inverse Simpson’s Index scores than those derived from Cell Ranger (10 × Genomics). We also applied our pipeline to multispecies multisample single-cell library containing breast cancer xenograft tissue and successfully identified all samples using genomic array and expression. Moreover, diverse cell types in the tumor microenvironment were well captured. Conclusion: We present our bioinformatics pipeline for mixed human and mouse single-cell data, which can also be applied to pooled libraries to obtain cost-effective single-cell data. We also address misalignment, multi-mapping error, and ambient RNA as a major consideration points when analyzing multispecies single-cell data....
Background: Quantification of gene expression from RNA-seq data is a prerequisite for transcriptome analysis such as differential gene expression analysis and gene coexpression network construction. Individual RNA-seq experiments are larger and combining multiple experiments from sequence repositories can result in datasets with thousands of samples. Processing hundreds to thousands of RNA-seq data can result in challenges related to data management, access to sufficient computational resources, navigation of high-performance computing (HPC) systems, installation of required software dependencies, and reproducibility. Processing of larger and deeper RNA-seq experiments will become more common as sequencing technology matures. Results: GEMmaker, is a nf-core compliant, Nextflow workflow, that quantifies gene expression from small to massive RNA-seq datasets. GEMmaker ensures results are highly reproducible through the use of versioned containerized software that can be executed on a single workstation, institutional compute cluster, Kubernetes platform or the cloud. GEMmaker supports popular alignment and quantification tools providing results in raw and normalized formats. GEMmaker is unique in that it can scale to process thousands of local or remote stored samples without exceeding available data storage. Conclusions: Workflows that quantify gene expression are not new, and many already address issues of portability, reusability, and scale in terms of access to CPUs. GEMmaker provides these benefits and adds the ability to scale despite low data storage infrastructure. This allows users to process hundreds to thousands of RNA-seq samples even when data storage resources are limited. GEMmaker is freely available and fully documented with step-by-step setup and execution instructions....
Background: Circular RNAs (circRNAs) play essential roles in cancer development and therapy resistance. Many studies have shown that circRNA is closely related to human health. The expression of circRNAs also affects the sensitivity of cells to drugs, thereby significantly affecting the efficacy of drugs. However, traditional biological experiments are time-consuming and expensive to validate drug-related circRNAs. Therefore, it is an important and urgent task to develop an effective computational method for predicting unknown circRNA-drug associations. Results: In this work, we propose a computational framework (GATECDA) based on graph attention auto-encoder to predict circRNA-drug sensitivity associations. In GATECDA, we leverage multiple databases, containing the sequences of host genes of circRNAs, the structure of drugs, and circRNA-drug sensitivity associations. Based on the data, GATECDA employs Graph attention auto-encoder (GATE) to extract the lowdimensional representation of circRNA/drug, effectively retaining critical information in sparse high-dimensional features and realizing the effective fusion of nodes’ neighborhood information. Experimental results indicate that GATECDA achieves an average AUC of 89.18% under 10-fold cross-validation. Case studies further show the excellent performance of GATECDA. Conclusions: Many experimental results and case studies show that our proposed GATECDA method can effectively predict the circRNA-drug sensitivity associations....
Background: Recent deep sequencing technologies have proven to be valuable resources to gain insights into the expression profiles of diverse tRNAs. However, despite these technologies, the association of tRNAs with diverse diseases has not been explored in depth because analytical tools are lacking. Results: We developed a user-friendly tool, tRNA Expression Analysis Software Utilizing R for Easy use (tReasure), to analyze differentially expressed tRNAs (DEtRNAs) from deep sequencing data of small RNAs using R packages. tReasure can quantify individual mature tRNAs, isodecoders, and isoacceptors. By adopting stringent mapping strategies, tReasure supports the precise measurement of mature tRNA read counts. The whole analysis workflow for determining DEtRNAs (uploading FASTQ files, removing adapter sequences and poor-quality reads, mapping and quantifying tRNAs, filtering out low count tRNAs, determining DEtRNAs, and visualizing statistical analysis) can be performed with the tReasure package. Conclusions: tReasure is an open-source software available for download at https:// treas ure. pmrc. re. kr and will be indispensable for users who have little experience with command-line software to explore the biological implication of tRNA expression....
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