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Data structures based on k-mers for querying large collections of sequencing data sets [REVIEW]

High-throughput sequencing data sets are usually deposited in public repositories (e.g., the European Nucleotide Archive) to ensure reproducibility. As the amount of data has reached petabyte scale, repositories do not allow one to perform online sequence searches, yet, such a feature would be highly useful to investigators. Toward this goal, in the...

Generation of mouse conditional knockout alleles in one step using the i-GONAD method [METHOD]

The Cre/loxP system is a powerful tool for gene function study in vivo. Regulated expression of Cre recombinase mediates precise deletion of genetic elements in a spatially– and temporally–controlled manner. Despite the robustness of this system, it requires a great amount of effort to create a conditional knockout model for each individual gene of...

Panoramic transcriptome analysis and functional screening of long noncoding RNAs in mouse spermatogenesis [RESEARCH]

Long noncoding RNAs (lncRNAs) have emerged as diverse functional regulators involved in mammalian development; however, large-scale functional investigation of lncRNAs in mammalian spermatogenesis in vivo is lacking. Here, we delineated the global lncRNA expression landscape in mouse spermatogenesis and identified 968 germ cell signature lncRNAs. By...

Predictive modeling of single-cell DNA methylome data enhances integration with transcriptome data [METHOD]

Single-cell DNA methylation data has become increasingly abundant and has uncovered many genes with a positive correlation between expression and promoter methylation, challenging the common dogma based on bulk data. However, computational tools for analyzing single-cell methylome data are lagging far behind. A number of tasks, including cell type calling...

Profiling neural editomes reveals a molecular mechanism to regulate RNA editing during development [RESEARCH]

Adenosine (A) to inosine (I) RNA editing contributes to transcript diversity and modulates gene expression in a dynamic, cell type–specific manner. During mammalian brain development, editing of specific adenosines increases, whereas the expression of A-to-I editing enzymes remains unchanged, suggesting molecular mechanisms that mediate spatiotemporal...

Gene expression imputation and cell-type deconvolution in human brain with spatiotemporal precision and its implications for brain-related disorders [RESOURCES]

As the most complex organ of the human body, the brain is composed of diverse regions, each consisting of distinct cell types and their respective cellular interactions. Human brain development involves a finely tuned cascade of interactive events. These include spatiotemporal gene expression changes and dynamic alterations in cell-type composition....

Thermal stress accelerates Arabidopsis thaliana mutation rate [RESEARCH]

Mutations are the source of both genetic diversity and mutational load. However, the effects of increasing environmental temperature on plant mutation rates and relative impact on specific mutational classes (e.g., insertion/deletion [indel] vs. single nucleotide variant [SNV]) are unknown. This topic is important because of the poorly defined effects...

Transcript assembly improves expression quantification of transposable elements in single-cell RNA-seq data [METHOD]

Transposable elements (TEs) are an integral part of the host transcriptome. TE-containing noncoding RNAs (ncRNAs) show considerable tissue specificity and play important roles during development, including stem cell maintenance and cell differentiation. Recent advances in single-cell RNA-seq (scRNA-seq) revolutionized cell type–specific gene expression...

The origin and evolution of a distinct mechanism of transcription initiation in yeasts [RESEARCH]

The molecular process of transcription by RNA Polymerase II is highly conserved among eukaryotes ("classic model"). A distinct way of locating transcription start sites (TSSs) has been identified in a budding yeast Saccharomyces cerevisiae ("scanning model"). Herein, we applied genomic approaches to elucidate the origin of the scanning model and its...

Greater strength of selection and higher proportion of beneficial amino acid changing mutations in humans compared with mice and Drosophila melanogaster [METHOD]

Quantifying and comparing the amount of adaptive evolution among different species is key to understanding how evolution works. Previous studies have shown differences in adaptive evolution across species; however, their specific causes remain elusive. Here, we use improved modeling of weakly deleterious mutations and the demographic history of the...

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