Tài liệu miễn phí Sinh học

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Gene editing of the multi-copy H2A.B gene and its importance for fertility

Altering the biochemical makeup of chromatin by the incorporation of histone variants during development represents a key mechanism in regulating gene expression. The histone variant H2A.B, H2A.B.3 in mice, appeared late in evolution and is most highly expressed in the testis.

4/6/2023 10:22:18 PM +00:00

Skmer: Assembly-free and alignment-free sample identification using genome skims

The ability to inexpensively describe taxonomic diversity is critical in this era of rapid climate and biodiversity changes. The recent genome-skimming approach extends current barcoding practices beyond short markers by applying low-pass sequencing and recovering whole organelle genomes computationally.

4/6/2023 10:22:10 PM +00:00

Genomic introgression through interspecific hybridization counteracts genetic bottleneck during soybean domestication

Evidence of introgression, the transfer of genetic material, between crops and their wild relatives through spontaneous hybridization and subsequent backcrossing has been documented; however, the evolutionary patterns and consequences of introgression and its influence on the processes of crop domestication and varietal diversification are poorly understood.

4/6/2023 10:22:02 PM +00:00

Prediction of functional microRNA targets by integrative modeling of microRNA binding and target expression data

We perform a large-scale RNA sequencing study to experimentally identify genes that are downregulated by 25 miRNAs. This RNA-seq dataset is combined with public miRNA target binding data to systematically identify miRNA targeting features that are characteristic of both miRNA binding and target downregulation.

4/6/2023 10:21:56 PM +00:00

Paleogenomics: Reconstruction of plant evolutionary trajectories from modern and ancient DNA

How contemporary plant genomes originated and evolved is a fascinating question. One approach uses reference genomes from extant species to reconstruct the sequence and structure of their common ancestors over deep timescales. A second approach focuses on the direct identification of genomic changes at a shorter timescale by sequencing ancient DNA preserved in subfossil remains.

4/6/2023 10:21:45 PM +00:00

Degradation of endogenous proteins and generation of a null-like phenotype in zebrafish using Trim-Away technology

Trim-Away is a recent technique to rapidly deplete a protein from any cell type. Guided by antibodies, TRIM21 selects proteins for destruction. However, the applicability of this method in model organisms has not been investigated. Here, we show that Trim-Away can degrade proteins in zebrafish embryos.

4/6/2023 10:21:38 PM +00:00

Multiple-gene targeting and mismatch tolerance can confound analysis of genome-wide pooled CRISPR screens

Genome-wide loss-of-function screens using the CRISPR/Cas9 system allow the efficient discovery of cancer cell vulnerabilities. While several studies have focused on correcting for DNA cleavage toxicity biases associated with copy number alterations, the effects of sgRNAs co-targeting multiple genomic loci in CRISPR screens have not been discussed.

4/6/2023 10:21:30 PM +00:00

Enhanced mammalian genome editing by new Cas12a orthologs with optimized crRNA scaffolds

CRISPR-Cas12a/Cpf1, a single RNA-guided endonuclease system, provides a promising tool for genome engineering. However, only three Cas12a orthologs have been employed for mammalian genome editing, and the editing efficiency as well as targeting coverage still requires improvements.

4/6/2023 10:21:22 PM +00:00

Systematic evaluation of C. elegans lincRNAs with CRISPR knockout mutants

Long intergenic RNAs (lincRNAs) play critical roles in eukaryotic cells, but systematic analyses of the lincRNAs of an animal for phenotypes are lacking. We generate CRISPR knockout strains for Caenorhabditis elegans lincRNAs and evaluate their phenotypes.

4/6/2023 10:21:15 PM +00:00

An amplicon-based sequencing framework for accurately measuring intrahost virus diversity using PrimalSeq and iVar

How viruses evolve within hosts can dictate infection outcomes; however, reconstructing this process is challenging. We evaluate our multiplexed amplicon approach, PrimalSeq, to demonstrate how virus concentration, sequencing coverage, primer mismatches, and replicates influence the accuracy of measuring intrahost virus diversity.

4/6/2023 10:21:03 PM +00:00

Population structure of human gut bacteria in a diverse cohort from rural Tanzania and Botswana

Gut microbiota from individuals in rural, non-industrialized societies differ from those in individuals from industrialized societies. Here, we use 16S rRNA sequencing to survey the gut bacteria of seven non-industrialized populations from Tanzania and Botswana.

4/6/2023 10:20:56 PM +00:00

Accurate prediction of cell type-specific transcription factor binding

Prediction of cell type-specific, in vivo transcription factor binding sites is one of the central challenges in regulatory genomics. Here, we present our approach that earned a shared first rank in the “ENCODE-DREAM in vivo Transcription Factor Binding Site Prediction Challenge” in 2017. In post-challenge analyses, we benchmark the influence of different feature sets and find that chromatin accessibility and binding motifs are sufficient to yield state-of-the-art performance.

4/6/2023 10:20:45 PM +00:00

GC-biased gene conversion conceals the prediction of the nearly neutral theory in avian genomes

The nearly neutral theory of molecular evolution predicts that the efficacy of natural selection increases with the effective population size. This prediction has been verified by independent observations in diverse taxa, which show that life-history traits are strongly correlated with measures of the efficacy of selection, such as the dN/dS ratio.

4/6/2023 10:20:39 PM +00:00

The Network of Cancer Genes (NCG): A comprehensive catalogue of known and candidate cancer genes from cancer sequencing screens

The Network of Cancer Genes (NCG) is a manually curated repository of 2372 genes whose somatic modifications have known or predicted cancer driver roles. These genes were collected from 275 publications, including two sources of known cancer genes and 273 cancer sequencing screens of more than 100 cancer types from 34,905 cancer donors and multiple primary sites.

4/6/2023 10:20:32 PM +00:00

Lifestyle modifications: Coordinating the tRNA epitranscriptome with codon bias to adapt translation during stress responses

Cells adapt to stress by altering gene expression at multiple levels. Here, we propose a new mechanism regulating stress-dependent gene expression at the level of translation, with coordinated interplay between the tRNA epitranscriptome and biased codon usage in families of stress-response genes.

4/6/2023 10:20:22 PM +00:00

Illuminating the genome-wide activity of genome editors for safe and effective therapeutics

Genome editing holds remarkable promise to transform human medicine as new therapies that can directly address the genetic causes of disease. However, concerns remain about possible undesired biological consequences of genome editors, particularly the introduction of unintended ‘off-target’ mutations.

4/6/2023 10:20:14 PM +00:00

Circadian oscillations of cytosine modification in humans contribute to epigenetic variability, aging, and complex disease

Maintenance of physiological circadian rhythm plays a crucial role in human health. Numerous studies have shown that disruption of circadian rhythm may increase risk for malignant, psychiatric, metabolic, and other diseases.

4/6/2023 10:20:07 PM +00:00

SCOPE-Seq: A scalable technology for linking live cell imaging and single-cell RNA sequencing

Optically decodable beads link the identity of a sample to a measurement through an optical barcode, enabling libraries of biomolecules to be captured on beads in solution and decoded by fluorescence. This approach has been foundational to microarray, sequencing, and flow-based expression profiling technologies.

4/6/2023 10:20:00 PM +00:00

Recombination of ecologically and evolutionarily significant loci maintains genetic cohesion in the Pseudomonas syringae species complex

Pseudomonas syringae is a highly diverse bacterial species complex capable of causing a wide range of serious diseases on numerous agronomically important crops. We examine the evolutionary relationships of 391 agricultural and environmental strains using whole-genome sequencing and evolutionary genomic analyses.

4/6/2023 10:19:53 PM +00:00

A comparative evaluation of hybrid error correction methods for error-prone long reads

Third-generation sequencing technologies have advanced the progress of the biological research by generating reads that are substantially longer than second-generation sequencing technologies. However, their notorious high error rate impedes straightforward data analysis and limits their application. A handful of error correction methods for these error-prone long reads have been developed to date.

4/6/2023 10:19:46 PM +00:00

Exosomal miR-196a derived from cancerassociated fibroblasts confers cisplatin resistance in head and neck cancer through targeting CDKN1B and ING5

Cisplatin resistance is a major challenge for advanced head and neck cancer (HNC). Understanding the underlying mechanisms and developing effective strategies against cisplatin resistance are highly desired in the clinic. However, how tumor stroma modulates HNC growth and chemoresistance is unclear.

4/6/2023 10:19:33 PM +00:00

Cell Hashing with barcoded antibodies enables multiplexing and doublet detection for single cell genomics

Despite rapid developments in single cell sequencing, sample-specific batch effects, detection of cell multiplets, and experimental costs remain outstanding challenges. Here, we introduce Cell Hashing, where oligo-tagged antibodies against ubiquitously expressed surface proteins uniquely label cells from distinct samples, which can be subsequently pooled.

4/6/2023 10:19:26 PM +00:00

Exploring the genetic basis of human population differences in DNA methylation and their causal impact on immune gene regulation

DNA methylation is influenced by both environmental and genetic factors and is increasingly thought to affect variation in complex traits and diseases. Yet, the extent of ancestry-related differences in DNA methylation, their genetic determinants, and their respective causal impact on immune gene regulation remain elusive.

4/6/2023 10:19:19 PM +00:00

Predicting age from the transcriptome of human dermal fibroblasts

Biomarkers of aging can be used to assess the health of individuals and to study aging and age-related diseases. We generate a large dataset of genome-wide RNA-seq profiles of human dermal fibroblasts from 133 people aged 1 to 94 years old to test whether signatures of aging are encoded within the transcriptome.

4/6/2023 10:19:12 PM +00:00

Analysis of 3D genomic interactions identifies candidate host genes that transposable elements potentially regulate

The organization of chromatin in the nucleus plays an essential role in gene regulation. About half of the mammalian genome comprises transposable elements. Given their repetitive nature, reads associated with these elements are generally discarded or randomly distributed among elements of the same type in genome-wide analyses.

4/6/2023 10:19:05 PM +00:00

Comparison of computational methods for the identification of topologically associating domains

Chromatin folding gives rise to structural elements among which are clusters of densely interacting DNA regions termed topologically associating domains (TADs). TADs have been characterized across multiple species, tissue types, and differentiation stages, sometimes in association with regulation of biological functions.

4/6/2023 10:18:58 PM +00:00

FORGe: Prioritizing variants for graph genomes

There is growing interest in using genetic variants to augment the reference genome into a graph genome, with alternative sequences, to improve read alignment accuracy and reduce allelic bias. While adding a variant has the positive effect of removing an undesirable alignment score penalty, it also increases both the ambiguity of the reference genome and the cost of storing and querying the genome index.

4/6/2023 10:18:51 PM +00:00

A novel FLI1 exonic circular RNA promotes metastasis in breast cancer by coordinately regulating TET1 and DNMT1

Friend leukemia virus integration 1 (FLI1), an ETS transcription factor family member, acts as an oncogenic driver in hematological malignancies and promotes tumor growth in solid tumors. However, little is known about the mechanisms underlying the activation of this proto-oncogene in tumors.

4/6/2023 10:18:43 PM +00:00

Understanding tumor ecosystems by single-cell sequencing: promises and limitations

Cellular heterogeneity within and across tumors has been a major obstacle in understanding and treating cancer, and the complex heterogeneity is masked if bulk tumor tissues are used for analysis.

4/6/2023 10:18:36 PM +00:00

NmeCas9 is an intrinsically high-fidelity genome-editing platform

The development of CRISPR genome editing has transformed biomedical research. Most applications reported thus far rely upon the Cas9 protein from Streptococcus pyogenes SF370 (SpyCas9). With many RNA guides, wildtype SpyCas9 can induce significant levels of unintended mutations at near-cognate sites, necessitating substantial efforts toward the development of strategies to minimize off-target activity.

4/6/2023 10:18:28 PM +00:00