Tài liệu miễn phí Sinh học
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Linked optical and gene expression profiling of single cells at high-throughput
Single-cell RNA sequencing has emerged as a powerful tool for characterizing cells, but not all phenotypes of interest can be observed through changes in gene expression. Linking sequencing with optical analysis has provided insight into the molecular basis of cellular function, but current approaches have limited throughput. Here, we present a high-throughput platform for linked optical and gene expression profiling of single cells.
4/6/2023 6:03:38 AM +00:00
Histone H3K27 acetylation is dispensable for enhancer activity in mouse embryonic stem cells
H3K27ac is well recognized as a marker for active enhancers and a great indicator of enhancer activity. However, its functional impact on transcription has not been characterized. By substituting lysine 27 in histone variant H3.3 with arginine in mouse embryonic stem cells, we diminish the vast majority of H3K27ac at enhancers.
4/6/2023 6:03:28 AM +00:00
Allosteric inhibition of CRISPR-Cas9 by bacteriophage-derived peptides
CRISPR-Cas9 has been developed as a therapeutic agent for various infectious and genetic diseases. In many clinically relevant applications, constitutively active CRISPR-Cas9 is delivered into human cells without a temporal control system. Excessive and prolonged expression of CRISPR-Cas9 can lead to elevated off-target cleavage.
4/6/2023 6:03:19 AM +00:00
NCHMR detector: A computational framework to systematically reveal nonclassical functions of histone modification regulators
Recently, several non-classical functions of histone modification regulators (HMRs), independent of their known histone modification substrates and products, have been reported to be essential for specific cellular processes. However, there is no framework designed for identifying such functions systematically.
4/6/2023 6:03:09 AM +00:00
A willow sex chromosome reveals convergent evolution of complex palindromic repeats
Sex chromosomes have arisen independently in a wide variety of species, yet they share common characteristics, including the presence of suppressed recombination surrounding sex determination loci. Mammalian sex chromosomes contain multiple palindromic repeats across the non-recombining region that show sequence conservation through gene conversion and contain genes that are crucial for sexual reproduction.
4/6/2023 6:03:00 AM +00:00
Decontamination of ambient RNA in single-cell RNA-seq with DecontX
Droplet-based microfluidic devices have become widely used to perform single-cell RNA sequencing (scRNA-seq). However, ambient RNA present in the cell suspension can be aberrantly counted along with a cell’s native mRNA and result in cross-contamination of transcripts between different cell populations.
4/6/2023 6:02:46 AM +00:00
Robustness and applicability of transcription factor and pathway analysis tools on single-cell RNA-seq data
Many functional analysis tools have been developed to extract functional and mechanistic insight from bulk transcriptome data. With the advent of single-cell RNA sequencing (scRNA-seq), it is in principle possible to do such an analysis for single cells. However, scRNA-seq data has characteristics such as drop-out events and low library sizes.
4/6/2023 6:02:39 AM +00:00
Regenerating zebrafish fin epigenome is characterized by stable lineage-specific DNA methylation and dynamic chromatin accessibility
Zebrafish can faithfully regenerate injured fins through the formation of a blastema, a mass of proliferative cells that can grow and develop into the lost body part. After amputation, various cell types contribute to blastema formation, where each cell type retains fate restriction and exclusively contributes to regeneration of its own lineage.
4/6/2023 6:02:28 AM +00:00
Admixture-enabled selection for rapid adaptive evolution in the Americas
Admixture occurs when previously isolated populations come together and exchange genetic material. We hypothesize that admixture can enable rapid adaptive evolution in human populations by introducing novel genetic variants (haplotypes) at intermediate frequencies, and we test this hypothesis through the analysis of whole genome sequences sampled from admixed Latin American populations in Colombia, Mexico, Peru, and Puerto Rico.
4/6/2023 6:02:20 AM +00:00
Protein velocity and acceleration from single-cell multiomics experiments
The simultaneous quantification of protein and RNA makes possible the inference of past, present, and future cell states from single experimental snapshots. To enable such temporal analysis from multimodal single-cell experiments, we introduce an extension of the RNA velocity method that leverages estimates of unprocessed transcript and protein abundances to extrapolate cell states.
4/6/2023 6:02:07 AM +00:00
A rare codon-based translational program of cell proliferation
The speed of translation elongation is primarily determined by the abundance of tRNAs. Thus, the codon usage influences the rate with which individual mRNAs are translated. As the nature of tRNA pools and modifications can vary across biological conditions, codon elongation rates may also vary, leading to fluctuations in the protein production from individual mRNAs.
4/6/2023 6:01:59 AM +00:00
A framework for transcriptome-wide association studies in breast cancer in diverse study populations
The relationship between germline genetic variation and breast cancer survival is largely unknown, especially in understudied minority populations who often have poorer survival. Genome-wide association studies (GWAS) have interrogated breast cancer survival but often are underpowered due to subtype heterogeneity and clinical covariates and detect loci in non-coding regions that are difficult to interpret.
4/6/2023 6:01:47 AM +00:00
Systematic functional identification of cancer multi-drug resistance genes
Drug resistance is a major obstacle in cancer therapy. To elucidate the genetic factors that regulate sensitivity to anti-cancer drugs, we performed CRISPR-Cas9 knockout screens for resistance to a spectrum of drugs.
4/6/2023 6:01:39 AM +00:00
Gscreend: Modelling asymmetric count ratios in CRISPR screens to decrease experiment size and improve phenotype detection
Pooled CRISPR screens are a powerful tool to probe genotype-phenotype relationships at genome-wide scale. However, criteria for optimal design are missing, and it remains unclear how experimental parameters affect results. Here, we report that random decreases in gRNA abundance are more likely than increases due to bottle-neck effects during the cell proliferation phase. Failure to consider this asymmetry leads to loss of detection power.
4/6/2023 6:01:30 AM +00:00
Nanopore sequencing-based genome assembly and evolutionary genomics of circum-basmati rice
The circum-basmati group of cultivated Asian rice (Oryza sativa) contains many iconic varieties and is widespread in the Indian subcontinent. Despite its economic and cultural importance, a high-quality reference genome is currently lacking, and the group’s evolutionary history is not fully resolved.
4/6/2023 6:01:19 AM +00:00
A post-transcriptional program of chemoresistance by AU-rich elements and TTP in quiescent leukemic cells
Quiescence (G0) is a transient, cell cycle-arrested state. By entering G0, cancer cells survive unfavorable conditions such as chemotherapy and cause relapse. While G0 cells have been studied at the transcriptome level, how post-transcriptional regulation contributes to their chemoresistance remains unknown.
4/6/2023 6:01:10 AM +00:00
Opportunities and challenges in long-read sequencing data analysis
Long-read sequencing technologies are overcoming early limitations in accuracy and throughput, broadening their application domains in genomics. Dedicated analysis tools that take into account the characteristics of long-read data are thus required, but the fast pace of development of such tools can be overwhelming.
4/6/2023 6:01:03 AM +00:00
Lisa: Inferring transcriptional regulators through integrative modeling of public chromatin accessibility and ChIP-seq data
Based on the input gene sets, Lisa first uses histone mark ChIP-seq and chromatin accessibility profiles to construct a chromatin model related to the regulation of these genes. Using TR ChIP-seq peaks or imputed TR binding sites, Lisa probes the chromatin models using in silico deletion to find the most relevant TRs.
4/6/2023 6:00:56 AM +00:00
Carnelian uncovers hidden functional patterns across diverse study populations from whole metagenome sequencing reads
Microbial populations exhibit functional changes in response to different ambient environments. Although whole metagenome sequencing promises enough raw data to study those changes, existing tools are limited in their ability to directly compare microbial metabolic function across samples and studies.
4/6/2023 6:00:49 AM +00:00
SCAI: An unsupervised approach for the integrative analysis of parallel single-cell transcriptomic and epigenomic profiles
Simultaneous measurements of transcriptomic and epigenomic profiles in the same individual cells provide an unprecedented opportunity to understand cell fates. However, effective approaches for the integrative analysis of such data are lacking.
4/6/2023 6:00:35 AM +00:00
CUBIC: An atlas of genetic architecture promises directed maize improvement
Identifying genotype-phenotype links and causative genes from quantitative trait loci (QTL) is challenging for complex agronomically important traits. To accelerate maize gene discovery and breeding, we present the Complete-diallel design plus Unbalanced Breeding-like Inter-Cross (CUBIC) population, consisting of 1404 individuals created by extensively inter-crossing 24 widely used Chinese maize founders.
4/6/2023 6:00:28 AM +00:00
Genome-wide MNase hypersensitivity assay unveils distinct classes of open chromatin associated with H3K27me3 and DNA methylation in Arabidopsis thaliana
Regulation of transcription depends on interactions between cis-regulatory elements (CREs) and regulatory proteins. Active CREs are imbedded in open chromatin that are accessible to nucleases. Several techniques, including DNase-seq, which is based on nuclease DNase I, and ATAC-seq, which is based on transposase Tn5, have been widely used to identify genomic regions associated with open chromatin
4/6/2023 6:00:16 AM +00:00
Eleven grand challenges in single-cell data science
The recent boom in microfluidics and combinatorial indexing strategies, combined with low sequencing costs, has empowered single-cell sequencing technology. Thousands—or even millions—of cells analyzed in a single experiment amount to a data revolution in single-cell biology and pose unique data science problems.
4/6/2023 6:00:07 AM +00:00
Gene content evolution in the arthropods
Arthropods comprise the largest and most diverse phylum on Earth and play vital roles in nearly every ecosystem. Their diversity stems in part from variations on a conserved body plan, resulting from and recorded in adaptive changes in the genome. Dissection of the genomic record of sequence change enables broad questions regarding genome evolution to be addressed, even across hyper-diverse taxa within arthropods.
4/6/2023 5:59:57 AM +00:00
A curated benchmark of enhancer-gene interactions for evaluating enhancer-target gene prediction methods
Many genome-wide collections of candidate cis-regulatory elements (cCREs) have been defined using genomic and epigenomic data, but it remains a major challenge to connect these elements to their target genes.
4/6/2023 5:59:48 AM +00:00
DENDRO: Genetic heterogeneity profiling and subclone detection by single-cell RNA sequencing
Although scRNA-seq is now ubiquitously adopted in studies of intratumor heterogeneity, detection of somatic mutations and inference of clonal membership from scRNA-seq is currently unreliable. We propose DENDRO, an analysis method for scRNA-seq data that clusters single cells into genetically distinct subclones and reconstructs the phylogenetic tree relating the subclones.
4/6/2023 5:59:38 AM +00:00
Enteric infection induces Lark-mediated intron retention at the 5′ end of Drosophila genes
RNA splicing is a key post-transcriptional mechanism that generates protein diversity and contributes to the fine-tuning of gene expression, which may facilitate adaptation to environmental challenges. Here, we employ a systems approach to study alternative splicing changes upon enteric infection in females from classical Drosophila melanogaster strains as well as 38 inbred lines.
4/6/2023 5:59:30 AM +00:00
HIFI: Estimating DNA-DNA interaction frequency from Hi-C data at restriction-fragment resolution
Hi-C is a popular technique to map three-dimensional chromosome conformation. In principle, Hi-C’s resolution is only limited by the size of restriction fragments. However, insufficient sequencing depth forces researchers to artificially reduce the resolution of Hi-C matrices at a loss of biological interpretability.
4/6/2023 5:59:21 AM +00:00
Host-associated microbiomes are predicted by immune system complexity and climate
Host-associated microbiomes, the microorganisms occurring inside and on host surfaces, influence evolutionary, immunological, and ecological processes. Interactions between host and microbiome affect metabolism and contribute to host adaptation to changing environments.
4/6/2023 5:59:09 AM +00:00
CHROMATIX: Computing the functional landscape of many-body chromatin interactions in transcriptionally active loci from deconvolved single cells
Chromatin interactions are important for gene regulation and cellular specialization. Emerging evidence suggests many-body spatial interactions play important roles in condensing super-enhancer regions into a cohesive transcriptional apparatus. Chromosome conformation studies using Hi-C are limited to pairwise, population-averaged interactions; therefore unsuitable for direct assessment of many-body interactions.
4/6/2023 5:59:00 AM +00:00