An aberrant immune-epithelial progenitor niche drives viral lung sequelae.

The long-term physiological consequences of respiratory viral infections, particularly in the aftermath of the COVID-19 pandemic-termed post-acute sequelae of SARS-CoV-2 (PASC)-are rapidly evolving into a major public health concern. While the cellular and molecular aetiologies of these sequelae are poorly defined, increasing evidence implicates abnormal immune responses and/or impaired organ recovery after infection. However, the precise mechanisms that link these processes in the context of PASC remain unclear.

Proximal immune-epithelial progenitor interactions drive chronic tissue sequelae post COVID-19.

The long-term physiological consequences of SARS-CoV-2, termed Post-Acute Sequelae of COVID-19 (PASC), are rapidly evolving into a major public health concern. The underlying cellular and molecular etiology remain poorly defined but growing evidence links PASC to abnormal immune responses and/or poor organ recovery post-infection. Yet, the precise mechanisms driving non-resolving inflammation and impaired tissue repair in the context of PASC remain unclear.

Single cell RNA sequencing unravels mechanisms underlying senescence-like phenotypes of alveolar macrophages.

Alveolar macrophages (AMs) are resident innate immune cells that play vital roles in maintaining lung physiological functions. However, the effects of aging on their dynamics, heterogeneity, and transcriptional profiles remain to be fully elucidated. Through single cell RNA sequencing (scRNA-seq), we identified CBFβ as an indispensable transcription factor that ensures AM self-renewal.

Extracellular cytochrome nanowires appear to be ubiquitous in prokaryotes.

Electrically conductive appendages from the anaerobic bacterium Geobacter sulfurreducens, recently identified as extracellular cytochrome nanowires (ECNs), have received wide attention due to numerous potential applications. However, whether other organisms employ similar ECNs for electron transfer remains unknown. Here, using cryoelectron microscopy, we describe the atomic structures of two ECNs from two major orders of hyperthermophilic archaea present in deep-sea hydrothermal vents and terrestrial hot springs.

Intrinsic bias estimation for improved analysis of bulk and single-cell chromatin accessibility profiles using SELMA.

Genome-wide profiling of chromatin accessibility by DNase-seq or ATAC-seq has been widely used to identify regulatory DNA elements and transcription factor binding sites. However, enzymatic DNA cleavage exhibits intrinsic sequence biases that confound chromatin accessibility profiling data analysis. Existing computational tools are limited in their ability to account for such intrinsic biases and not designed for analyzing single-cell data.

Single-cell chromatin profiling of the primitive gut tube reveals regulatory dynamics underlying lineage fate decisions.

Development of the gastrointestinal system occurs after gut tube closure, guided by spatial and temporal control of gene expression. However, it remains unclear what forces regulate these spatiotemporal gene expression patterns. Here we perform single-cell chromatin profiling of the primitive gut tube to reveal organ-specific chromatin patterns that reflect the anatomical patterns of distinct organs.

Single-nucleus chromatin accessibility profiling highlights regulatory mechanisms of coronary artery disease risk.

Coronary artery disease (CAD) is a complex inflammatory disease involving genetic influences across cell types. Genome-wide association studies have identified over 200 loci associated with CAD, where the majority of risk variants reside in noncoding DNA sequences impacting cis-regulatory elements. Here, we applied single-nucleus assay for transposase-accessible chromatin with sequencing to profile 28,316 nuclei across coronary artery segments from 41 patients with varying stages of CAD, which revealed 14 distinct cellular clusters.

Stuck-moving needle acupuncture myofascial trigger point to treat idiopathic frozen shoulder: study protocol for a randomized controlled trial.

Background: There are evidence for the efficacy of acupuncture treatment for chronic shoulder pain, however, it remains unclear the best acupuncture modes for effective treatment. We compared the effect of the myofascial trigger point (MTrp) stuck-moving needle acupuncture with that of common acupuncture treatments. Further, we evaluated the efficacy and safety of stuck-moving needle acupuncture for the MTrp in improving pain and range of motions in patients with idiopathic frozen shoulder.

Ectopic Tcf1 expression instills a stem-like program in exhausted CD8 T cells to enhance viral and tumor immunity.

Exhausted CD8 T (Tex) cells are dysfunctional due to persistent antigen exposure in chronic viral infection and tumor contexts. A stem cell-like Tex (Tex-stem) subset can self-renew and differentiate into terminally exhausted (Tex-term) cells. Here, we show that ectopic Tcf1 expression potently promoted the generation of Tex-stem cells in both a chronic viral infection and preclinical tumor models.

ncHMR detector: a computational framework to systematically reveal non-classical 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. Here, we develop ncHMR detector, the first computational framework to predict non-classical functions and cofactors of a given HMR, based on ChIP-seq data mining.

Inherited DNA methylation primes the establishment of accessible chromatin during genome activation.

For animals, epigenetic modifications can be globally or partially inherited from gametes after fertilization, and such information is required for proper transcriptional regulation, especially during the process of zygotic genome activation (ZGA). However, the mechanism underlying how the inherited epigenetic signatures affect transcriptional regulation during ZGA remains poorly understood. Here, we performed genome-wide profiling of chromatin accessibility during zebrafish ZGA, which is closely related to zygotic transcriptional regulation.

CAM: A quality control pipeline for MNase-seq data.

Nucleosome organization affects the accessibility of cis-elements to trans-acting factors. Micrococcal nuclease digestion followed by high-throughput sequencing (MNase-seq) is the most popular technology used to profile nucleosome organization on a genome-wide scale. Evaluating the data quality of MNase-seq data remains challenging, especially in mammalian.

Dr.seq2: A quality control and analysis pipeline for parallel single cell transcriptome and epigenome data.

An increasing number of single cell transcriptome and epigenome technologies, including single cell ATAC-seq (scATAC-seq), have been recently developed as powerful tools to analyze the features of many individual cells simultaneously. However, the methods and software were designed for one certain data type and only for single cell transcriptome data. A systematic approach for epigenome data and multiple types of transcriptome data is needed to control data quality and to perform cell-to-cell heterogeneity analysis on these ultra-high-dimensional transcriptome and epigenome datasets.

CRISPR-DO for genome-wide CRISPR design and optimization.

Motivation: Despite the growing popularity in using CRISPR/Cas9 technology for genome editing and gene knockout, its performance still relies on well-designed single guide RNAs (sgRNA). In this study, we propose a web application for the Design and Optimization (CRISPR-DO) of guide sequences that target both coding and non-coding regions in spCas9 CRISPR system across human, mouse, zebrafish, fly and worm genomes. CRISPR-DO uses a computational sequence model to predict sgRNA efficiency, and employs a specificity scoring function to evaluate the potential of off-target effect.

Dr.seq: a quality control and analysis pipeline for droplet sequencing.

Motivation: Drop-seq has recently emerged as a powerful technology to analyze gene expression from thousands of individual cells simultaneously. Currently, Drop-seq technology requires refinement and quality control (QC) steps are critical for such data analysis. There is a strong need for a convenient and comprehensive approach to obtain dedicated QC and to determine the relationships between cells for ultra-high-dimensional datasets.

High-dimensional genomic data bias correction and data integration using MANCIE.

High-dimensional genomic data analysis is challenging due to noises and biases in high-throughput experiments. We present a computational method matrix analysis and normalization by concordant information enhancement (MANCIE) for bias correction and data integration of distinct genomic profiles on the same samples. MANCIE uses a Bayesian-supported principal component analysis-based approach to adjust the data so as to achieve better consistency between sample-wise distances in the different profiles.

Integrative Analysis Reveals the Transcriptional Collaboration between EZH2 and E2F1 in the Regulation of Cancer-Related Gene Expression.

Unlabelled: Overexpression of EZH2 is frequently linked to the advanced and metastatic stage of cancers. The mechanisms of its oncogenic function can be context specific, and may vary depending on the protein complexes that EZH2 interacts with. To identify novel transcriptional collaborators of EZH2 in cancers, a computational approach was developed that integrates protein-DNA binding data, cell perturbation gene expression data, and compendiums of tumor expression profiles.

Comparative analysis of metazoan chromatin organization.

Genome function is dynamically regulated in part by chromatin, which consists of the histones, non-histone proteins and RNA molecules that package DNA. Studies in Caenorhabditis elegans and Drosophila melanogaster have contributed substantially to our understanding of molecular mechanisms of genome function in humans, and have revealed conservation of chromatin components and mechanisms. Nevertheless, the three organisms have markedly different genome sizes, chromosome architecture and gene organization.