Tài liệu miễn phí Sinh học
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Characterisation of genetic regulatory effects for osteoporosis risk variants in human osteoclasts
Osteoporosis is a complex disease with a strong genetic contribution. A recently published genomewide association study (GWAS) for estimated bone mineral density (eBMD) identified 1103 independent genomewide significant association signals. Most of these variants are non-coding, suggesting that regulatory effects may drive many of the associations.
4/6/2023 6:07:52 AM +00:00
Insights gained from a comprehensive allagainst-all transcription factor binding motif benchmarking study
Positional weight matrix (PWM) is a de facto standard model to describe transcription factor (TF) DNA binding specificities. PWMs inferred from in vivo or in vitro data are stored in many databases and used in a plethora of biological applications. This calls for comprehensive benchmarking of public PWM models with large experimental reference sets.
4/6/2023 6:07:44 AM +00:00
Varlociraptor: Enhancing sensitivity and controlling false discovery rate in somatic indel discovery
Accurate discovery of somatic variants is of central importance in cancer research. However, count statistics on discovered somatic insertions and deletions (indels) indicate that large amounts of discoveries are missed because of the quantification of uncertainties related to gap and alignment ambiguities, twilight zone indels, cancer heterogeneity, sample purity, sampling, and strand bias.
4/6/2023 6:07:36 AM +00:00
TADsplimer reveals splits and mergers of topologically associating domains for epigenetic regulation of transcription
We present TADsplimer, the first computational tool to systematically detect topologically associating domain (TAD) splits and mergers across the genome between Hi-C samples. TADsplimer recaptures splits and mergers of TADs with high accuracy in simulation analyses and defines hundreds of TAD splits and mergers between pairs of different cell types, such as endothelial cells and fibroblasts.
4/6/2023 6:07:29 AM +00:00
Successful generation of epigenetic disease model mice by targeted demethylation of the epigenome
Epigenetic modifications, including DNA methylation, play an important role in gene silencing and genome stability. Consequently, epigenetic dysregulation can cause several diseases, such as cancer, obesity, diabetes, autism, and imprinting disorders.
4/6/2023 6:07:19 AM +00:00
A multidimensional systems biology analysis of cellular senescence in aging and disease
Cellular senescence, a permanent state of replicative arrest in otherwise proliferating cells, is a hallmark of aging and has been linked to aging-related diseases. Many genes play a role in cellular senescence, yet a comprehensive understanding of its pathways is still lacking.
4/6/2023 6:07:11 AM +00:00
A Cas12a ortholog with stringent PAM recognition followed by low off-target editing rates for genome editing
AsCas12a and LbCas12a nucleases are reported to be promising tools for genome engineering with protospacer adjacent motif (PAM) TTTV as the optimal. However, the C-containing PAM (CTTV, TCTV, TTCV, etc.) recognition by Cas12a might induce extra off-target edits at these non-canonical PAM sites.
4/6/2023 6:07:01 AM +00:00
Benchmarking of computational errorcorrection methods for next-generation sequencing data
Recent advancements in next-generation sequencing have rapidly improved our ability to study genomic material at an unprecedented scale. Despite substantial improvements in sequencing technologies, errors present in the data still risk confounding downstream analysis and limiting the applicability of sequencing technologies in clinical tools.
4/6/2023 6:06:54 AM +00:00
DeepMILO: A deep learning approach to predict the impact of non-coding sequence variants on 3D chromatin structure
Non-coding variants have been shown to be related to disease by alteration of 3D genome structures. We propose a deep learning method, DeepMILO, to predict the effects of variants on CTCF/cohesin-mediated insulator loops. Application of DeepMILO on variants from whole-genome sequences of 1834 patients of twelve cancer types revealed 672 insulator loops disrupted in at least 10% of patients.
4/6/2023 6:06:48 AM +00:00
HiNT: A computational method for detecting copy number variations and translocations from Hi-C data
The three-dimensional conformation of a genome can be profiled using Hi-C, a technique that combines chromatin conformation capture with high-throughput sequencing. However, structural variations often yield features that can be mistaken for chromosomal interactions.
4/6/2023 6:06:40 AM +00:00
High-resolution Repli-Seq defines the temporal choreography of initiation, elongation and termination of replication in mammalian cells
DNA replication in mammalian cells occurs in a defined temporal order during S phase, known as the replication timing (RT) programme. Replication timing is developmentally regulated and correlated with chromatin conformation and local transcriptional potential.
4/6/2023 6:06:33 AM +00:00
Principles of RNA processing from analysis of enhanced CLIP maps for 150 RNA binding proteins
A critical step in uncovering rules of RNA processing is to study the in vivo regulatory networks of RNA binding proteins (RBPs). Crosslinking and immunoprecipitation (CLIP) methods enable mapping RBP targets transcriptome-wide, but methodological differences present challenges to large-scale analysis across datasets.
4/6/2023 6:06:20 AM +00:00
Obstacles to detecting isoforms using full-length scRNA-seq data
Early single-cell RNA-seq (scRNA-seq) studies suggested that it was unusual to see more than one isoform being produced from a gene in a single cell, even when multiple isoforms were detected in matched bulk RNA-seq samples. However, these studies generally did not consider the impact of dropouts or isoform quantification errors, potentially confounding the results of these analyses.
4/6/2023 6:06:11 AM +00:00
Diverse genetic mechanisms underlie worldwide convergent rice feralization
Worldwide feralization of crop species into agricultural weeds threatens global food security. Weedy rice is a feral form of rice that infests paddies worldwide and aggressively outcompetes cultivated varieties. Despite increasing attention in recent years, a comprehensive understanding of the origins of weedy crop relatives and how a universal feralization process acts at the genomic and molecular level to allow the rapid adaptation to weediness are still yet to be explored.
4/6/2023 6:06:02 AM +00:00
RADAR: Annotation and prioritization of variants in the post-transcriptional regulome of RNA-binding proteins
RNA-binding proteins (RBPs) play key roles in post-transcriptional regulation and disease. Their binding sites cover more of the genome than coding exons; nevertheless, most noncoding variant prioritization methods only focus on transcriptional regulation. Here, we integrate the portfolio of ENCODE-RBP experiments to develop RADAR, a variant-scoring framework.
4/6/2023 6:05:55 AM +00:00
Smarcad1 mediates microbiota-induced inflammation in mouse and coordinates gene expression in the intestinal epithelium
How intestinal epithelial cells interact with the microbiota and how this is regulated at the gene expression level are critical questions. Smarcad1 is a conserved chromatin remodeling factor with a poorly understood tissue function. As this factor is highly expressed in the stem and proliferative zones of the intestinal epithelium, we explore its role in this tissue.
4/6/2023 6:05:45 AM +00:00
VALOR2: Characterization of large-scale structural variants using linked-reads
Most existing methods for structural variant detection focus on discovery and genotyping of deletions, insertions, and mobile elements. Detection of balanced structural variants with no gain or loss of genomic segments, for example, inversions and translocations, is a particularly challenging task. Furthermore, there are very few algorithms to predict the insertion locus of large interspersed segmental duplications and characterize translocations.
4/6/2023 6:05:38 AM +00:00
Ultraplexing: increasing the efficiency of long-read sequencing for hybrid assembly with k-mer-based multiplexing
Hybrid genome assembly has emerged as an important technique in bacterial genomics, but cost and labor requirements limit large-scale application. We present Ultraplexing, a method to improve per-sample sequencing cost and hands-on time of Nanopore sequencing for hybrid assembly by at least 50% compared to molecular barcoding while maintaining high assembly quality.
4/6/2023 6:05:31 AM +00:00
Multiplexed capture of spatial configuration and temporal dynamics of locus-specific 3D chromatin by biotinylated dCas9
The spatiotemporal control of 3D genome is fundamental for gene regulation, yet it remains challenging to profile high-resolution chromatin structure at cis-regulatory elements (CREs). Using C-terminally biotinylated dCas9, endogenous biotin ligases, and pooled sgRNAs, we describe the dCas9-based CAPTURE method for multiplexed analysis of locus-specific chromatin interactions.
4/6/2023 6:05:22 AM +00:00
A benchmark of algorithms for the analysis of pooled CRISPR screens
Genome-wide pooled CRISPR-Cas-mediated knockout, activation, and repression screens are powerful tools for functional genomic investigations. Despite their increasing importance, there is currently little guidance on how to design and analyze CRISPR-pooled screens.
4/6/2023 6:05:11 AM +00:00
High-resolution modeling of the selection on local mRNA folding strength in coding sequences across the tree of life
mRNA can form local secondary structure within the protein-coding sequence, and the strength of this structure is thought to influence gene expression regulation. Previous studies suggest that secondary structure strength may be maintained under selection, but the details of this phenomenon are not well understood.
4/6/2023 6:05:02 AM +00:00
Accurate targeted long-read DNA methylation and hydroxymethylation sequencing with TAPS
We present long-read Tet-assisted pyridine borane sequencing (lrTAPS) for targeted base-resolution sequencing of DNA methylation and hydroxymethylation in regions up to 10 kb from nanogram-level input. Compatible with both Oxford Nanopore and PacBio Single-Molecule Real-Time (SMRT) sequencing, lrTAPS detects methylation with accuracy comparable to short-read Illumina sequencing but with long-range epigenetic phasing.
4/6/2023 6:04:55 AM +00:00
NanoVar: Accurate characterization of patients’ genomic structural variants using low-depth nanopore sequencing
The recent advent of third-generation sequencing technologies brings promise for better characterization of genomic structural variants by virtue of having longer reads. However, long-read applications are still constrained by their high sequencing error rates and low sequencing throughput.
4/6/2023 6:04:45 AM +00:00
BANDITS: Bayesian differential splicing accounting for sample-to-sample variability and mapping uncertainty
Alternative splicing is a biological process during gene expression that allows a single gene to code for multiple proteins. However, splicing patterns can be altered in some conditions or diseases. Here, we present BANDITS, a R/Bioconductor package to perform differential splicing, at both gene and transcript level, based on RNA-seq data.
4/6/2023 6:04:35 AM +00:00
Decode-seq: A practical approach to improve differential gene expression analysis
Many differential gene expression analyses are conducted with an inadequate number of biological replicates. We describe an easy and effective RNA-seq approach using molecular barcoding to enable profiling of a large number of replicates simultaneously.
4/6/2023 6:04:25 AM +00:00
WhatsGNU: A tool for identifying proteomic novelty
To understand diversity in enormous collections of genome sequences, we need computationally scalable tools that can quickly contextualize individual genomes based on their similarities and identify features of each genome that make them unique.
4/6/2023 6:04:18 AM +00:00
Longitudinal survey of microbiome associated with particulate matter in a megacity
While the physical and chemical properties of airborne particulate matter (PM) have been extensively studied, their associated microbiome remains largely unexplored. Here, we performed a longitudinal metagenomic survey of 106 samples of airborne PM2.5 and PM10 in Beijing over a period of 6 months in 2012 and 2013, including those from several historically severe smog events.
4/6/2023 6:04:11 AM +00:00
CHOP: Haplotype-aware path indexing in population graphs
The practical use of graph-based reference genomes depends on the ability to align reads to them. Performing substring queries to paths through these graphs lies at the core of this task. The combination of increasing pattern length and encoded variations inevitably leads to a combinatorial explosion of the search space.
4/6/2023 6:04:04 AM +00:00
Hemispheric asymmetry in the human brain and in Parkinson’s disease is linked to divergent epigenetic patterns in neurons
Hemispheric asymmetry in neuronal processes is a fundamental feature of the human brain and drives symptom lateralization in Parkinson’s disease (PD), but its molecular determinants are unknown. Here, we identify divergent epigenetic patterns involved in hemispheric asymmetry by profiling DNA methylation in isolated prefrontal cortex neurons from control and PD brain hemispheres.
4/6/2023 6:03:56 AM +00:00
The genome evolution and domestication of tropical fruit mango
Mango is one of the world’s most important tropical fruits. It belongs to the family Anacardiaceae, which includes several other economically important species, notably cashew, sumac and pistachio from other genera. Many species in this family produce family-specific urushiols and related phenols, which can induce contact dermatitis.
4/6/2023 6:03:48 AM +00:00