Tài liệu miễn phí Sinh học

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Computational biologists: Moving to the driver's seat

The recent shift of computational biologists from bioinformatics service providers to leaders of cutting-edge programs highlights the accompanying cultural and conceptual changes that should be implemented by funding bodies and academic institutions.

4/6/2023 6:40:21 AM +00:00

OMSV enables accurate and comprehensive identification of large structural variations from nanochannel-based single-molecule optical maps

We present a new method, OMSV, for accurately and comprehensively identifying structural variations (SVs) from optical maps. OMSV detects both homozygous and heterozygous SVs, SVs of various types and sizes, and SVs with or without creating or destroying restriction sites. We show that OMSV has high sensitivity and specificity, with clear performance gains over the latest method.

4/6/2023 6:40:14 AM +00:00

Rescue of high-specificity Cas9 variants using sgRNAs with matched 5’ nucleotides

We report that engineered Cas9 variants with improved specificity—eCas9-1.1 and Cas9-HF1—are often poorly active in human cells, when complexed with single guide RNAs (sgRNAs) with a mismatch at the 5’ terminus, relative to target DNA sequences. Because the nucleotide at the 5’ end of sgRNAs, expressed under the control of the commonly-used U6 promoter, is fixed to a guanine, these attenuated Cas9 variants are not useful at many target sites.

4/6/2023 6:40:07 AM +00:00

CRISPR/Cas9-mediated targeted chromosome elimination

The CRISPR/Cas9 system has become an efficient gene editing method for generating cells carrying precise gene mutations, including the rearrangement and deletion of chromosomal segments. However, whether an entire chromosome could be eliminated by this technology is still unknown.

4/6/2023 6:39:52 AM +00:00

Evaluation of in silico algorithms for use with ACMG/AMP clinical variant interpretation guidelines

The American College of Medical Genetics and American College of Pathologists (ACMG/AMP) variant classification guidelines for clinical reporting are widely used in diagnostic laboratories for variant interpretation. The ACMG/AMP guidelines recommend complete concordance of predictions among all in silico algorithms used without specifying the number or types of algorithms.

4/6/2023 6:39:45 AM +00:00

Early career researchers want Open Science

Open Science is encouraged by the European Union and many other political and scientific institutions. However, scientific practice is proving slow to change. We propose, as early career researchers, that it is our task to change scientific research into open scientific research and commit to Open Science principles.

4/6/2023 6:39:38 AM +00:00

Forebrain-specific, conditional silencing of Staufen2 alters synaptic plasticity, learning, and memory in rats

Dendritic messenger RNA (mRNA) localization and subsequent local translation in dendrites critically contributes to synaptic plasticity and learning and memory. Little is known, however, about the contribution of RNA-binding proteins (RBPs) to these processes in vivo.

4/6/2023 6:39:32 AM +00:00

XCell: Digitally portraying the tissue cellular heterogeneity landscape

Tissues are complex milieus consisting of numerous cell types. Several recent methods have attempted to enumerate cell subsets from transcriptomes. However, the available methods have used limited sources for training and give only a partial portrayal of the full cellular landscape. Here we present xCell, a novel gene signature-based method, and use it to infer 64 immune and stromal cell types.

4/6/2023 6:39:24 AM +00:00

The multidimensional mechanisms of long noncoding RNA function

A major shift in our understanding of genome regulation has emerged recently. It is now apparent that the majority of cellular transcripts do not code for proteins, and many of them are long noncoding RNAs (lncRNAs). Increasingly, studies suggest that lncRNAs regulate gene expression through diverse mechanisms. We review emerging mechanistic views of lncRNAs in gene regulation in the cell nucleus.

4/6/2023 6:39:15 AM +00:00

Rewriting the transcriptome: Adenosine-toinosine RNA editing by ADARs

One of the most prevalent forms of post-transcritpional RNA modification is the conversion of adenosine nucleosides to inosine (A-to-I), mediated by the ADAR family of enzymes. The functional requirement and regulatory landscape for the majority of A-to-I editing events are, at present, uncertain.

4/6/2023 6:39:08 AM +00:00

The interplay of demography and selection during maize domestication and expansion

The history of maize has been characterized by major demographic events, including population size changes associated with domestication and range expansion, and gene flow with wild relatives. The interplay between demographic history and selection has shaped diversity across maize populations and genomes.

4/6/2023 6:39:01 AM +00:00

Functional assessment of human enhancer activities using whole-genome STARRsequencing

Genome-wide quantification of enhancer activity in the human genome has proven to be a challenging problem. Recent efforts have led to the development of powerful tools for enhancer quantification. However, because of genome size and complexity, these tools have yet to be applied to the whole human genome.

4/6/2023 6:38:46 AM +00:00

The fitness cost of mis-splicing is the main determinant of alternative splicing patterns

Most eukaryotic genes are subject to alternative splicing (AS), which may contribute to the production of protein variants or to the regulation of gene expression via nonsense-mediated messenger RNA (mRNA) decay (NMD).

4/6/2023 6:38:39 AM +00:00

Promoting RNA editing by ADAR attraction

Concentration is important and not only while driving; A new study indicates how an adjacent genomic element helps to increase the efficiency of a specific adenosine to inosine RNA editing reaction, by providing a means to increase the local concentration of the RNA editing enzyme ADAR.

4/6/2023 6:38:29 AM +00:00

Long-term balancing selection contributes to adaptation in Arabidopsis and its relatives

In contrast to positive selection, which reduces genetic variation by fixing beneficial alleles, balancing selection maintains genetic variation within a population or species and plays crucial roles in adaptation in diverse organisms. However, which genes, genome-wide, are under balancing selection and the extent to which these genes are involved in adaptation are largely unknown.

4/6/2023 6:38:19 AM +00:00

New reference genome sequences of hot pepper reveal the massive evolution of plant disease-resistance genes by retroduplication

Transposable elements are major evolutionary forces which can cause new genome structure and species diversification. The role of transposable elements in the expansion of nucleotide-binding and leucine-rich-repeat proteins (NLRs), the major disease-resistance gene families, has been unexplored in plants.

4/6/2023 6:38:09 AM +00:00

ScDual-Seq: Mapping the gene regulatory program of Salmonella infection by host and pathogen single-cell RNA-sequencing

The interaction between a pathogen and a host is a highly dynamic process in which both agents activate complex programs. Here, we introduce a single-cell RNA-sequencing method, scDual-Seq, that simultaneously captures both host and pathogen transcriptomes.

4/6/2023 6:38:02 AM +00:00

Intron retention enhances gene regulatory complexity in vertebrates

While intron retention (IR) is now widely accepted as an important mechanism of mammalian gene expression control, it remains the least studied form of alternative splicing. To delineate conserved features of IR, we performed an exhaustive phylogenetic analysis in a highly purified and functionally defined cell type comprising neutrophilic granulocytes from five vertebrate species spanning 430 million years of evolution.

4/6/2023 6:37:52 AM +00:00

Dynamic changes in eIF4F-mRNA interactions revealed by global analyses of environmental stress responses

Translation factors eIF4E and eIF4G form eIF4F, which interacts with the messenger RNA (mRNA) 5′ cap to promote ribosome recruitment and translation initiation. Variations in the association of eIF4F with individual mRNAs likely contribute to differences in translation initiation frequencies between mRNAs.

4/6/2023 6:37:40 AM +00:00

Depletion of somatic mutations in splicingassociated sequences in cancer genomes

An important goal of cancer genomics is to identify systematically cancer-causing mutations. A common approach is to identify sites with high ratios of non-synonymous to synonymous mutations; however, if synonymous mutations are under purifying selection, this methodology leads to identification of false-positive mutations.

4/6/2023 6:37:32 AM +00:00

Epitranscriptomic influences on development and disease

A contains over 150 types of chemical modifications. Although many of these chemical modifications were discovered several decades ago, their functions were not immediately apparent. Discoveries of RNA demethylases, along with advances in mass spectrometry and high-throughput sequencing techniques, have caused research into RNA modifications to progress at an accelerated rate.

4/6/2023 6:37:25 AM +00:00

Regulatory remodeling in the allo-tetraploid frog Xenopus laevis

Genome duplication has played a pivotal role in the evolution of many eukaryotic lineages, including the vertebrates. A relatively recent vertebrate genome duplication is that in Xenopus laevis, which resulted from the hybridization of two closely related species about 17 million years ago.

4/6/2023 6:37:15 AM +00:00

F-scLVM: Scalable and versatile factor analysis for single-cell RNA-seq

Single-cell RNA-sequencing (scRNA-seq) allows studying heterogeneity in gene expression in large cell populations. Such heterogeneity can arise due to technical or biological factors, making decomposing sources of variation difficult. We here describe f-scLVM (factorial single-cell latent variable model), a method based on factor analysis that uses pathway annotations to guide the inference of interpretable factors underpinning the heterogeneity.

4/6/2023 6:37:05 AM +00:00

Comparative epigenomics in the Brassicaceae reveals two evolutionarily conserved modes of PRC2-mediated gene regulation

Polycomb Repressive Complexes 2 (PRC2) are multi-protein chromatin modifiers that are evolutionarily conserved among eukaryotes and play key roles in the regulation of gene expression, notably through the trimethylation of lysine 27 of histone H3 (H3K27me3). Although PRC2-mediated gene regulation has been studied in many organisms, few studies have explored in depth the evolutionary conservation of PRC2 targets.

4/6/2023 6:36:55 AM +00:00

Adaptation of iCLIP to plants determines the binding landscape of the clockregulated RNA-binding protein AtGRP7

Functions for RNA-binding proteins in orchestrating plant development and environmental responses are well established. However, the lack of a genome-wide view of their in vivo binding targets and binding landscapes represents a gap in understanding the mode of action of plant RNA-binding proteins.

4/6/2023 6:36:46 AM +00:00

The human lncRNA LINC-PINT inhibits tumor cell invasion through a highly conserved sequence element

It is now obvious that the majority of cellular transcripts do not code for proteins, and a significant subset of them are long non-coding RNAs (lncRNAs). Many lncRNAs show aberrant expression in cancer, and some of them have been linked to cell transformation. However, the underlying mechanisms remain poorly understood and it is unknown how the sequences of lncRNA dictate their function

4/6/2023 6:36:39 AM +00:00

The influence of microRNAs and poly(A) tail length on endogenous mRNA–protein complexes

All mRNAs are bound in vivo by proteins to form mRNA–protein complexes (mRNPs), but changes in the composition of mRNPs during posttranscriptional regulation remain largely unexplored. Here, we have analyzed, on a transcriptome-wide scale, how microRNA-mediated repression modulates the associations of the core mRNP components eIF4E, eIF4G, and PABP and of the decay factor DDX6 in human cells.

4/6/2023 6:36:32 AM +00:00

Widespread activation of antisense transcription of the host genome during herpes simplex virus 1 infection

Herpesviruses can infect a wide range of animal species. Herpes simplex virus 1 (HSV-1) is one of the eight herpesviruses that can infect humans and is prevalent worldwide. Herpesviruses have evolved multiple ways to adapt the infected cells to their needs, but knowledge about these transcriptional and post-transcriptional modifications is sparse.

4/6/2023 6:36:23 AM +00:00

Meiotic crossovers are associated with open chromatin and enriched with Stowaway transposons in potato

Meiotic recombination is the foundation for genetic variation in natural and artificial populations of eukaryotes. Although genetic maps have been developed for numerous plant species since the late 1980s, few of these maps have provided the necessary resolution needed to investigate the genomic and epigenomic features underlying meiotic crossovers.

4/6/2023 6:36:16 AM +00:00

Perfectly matched 20-nucleotide guide RNA sequences enable robust genome editing using high-fidelity SpCas9 nucleases

High-fidelity SpCas9 variants (eSpCas9 and SpCas9-HF1) have been engineered to reduce off-target effects. We found that changes in guide RNA length induced significant reductions in the editing activities of SpCas9 variants in plant cells.

4/6/2023 6:36:09 AM +00:00