Leveraging large-scale multi-omics evidences to identify therapeutic targets from genome-wide association studies.

Background: Therapeutic targets supported by genetic evidence from genome-wide association studies (GWAS) show higher probability of success in clinical trials. GWAS is a powerful approach to identify links between genetic variants and phenotypic variation; however, identifying the genes driving associations identified in GWAS remains challenging. Integration of molecular quantitative trait loci (molQTL) such as expression QTL (eQTL) using mendelian randomization (MR) and colocalization analyses can help with the identification of causal genes.

The IL-4-IL-4Rα axis modulates olfactory neuroimmune signaling to induce loss of smell.

IL-4 and IL-13 have non-redundant effects in olfaction, with loss of smell in mice evoked only by intranasal administration of IL-4, but not IL-13. IL-4-evoked pathophysiological effects on olfaction is independent of compromised structural integrity of the olfactory neuroepithelium. IL-4-IL-4Rα signaling modulates neuronal crosstalk with immune cells, suggesting a functional link between olfactory impairment and neuroinflammation.

Discectomy versus sequestrectomy in the treatment of lumbar disc herniation: a systematic review and meta-analysis.

Background Context: Lumbar disc herniation (LDH) is a leading cause of low back pain (LBP) and leg pain and may require surgical treatment in case of persistent pain and/or neurological deficits. Conventional discectomy involves removing the herniated fragment and additional material from the disc space, potentially accelerating disc degeneration and contributing to chronic LBP. Conversely, by resecting the herniated fragment only, sequestrectomy may reduce postoperative LBP while increasing the risk of LDH recurrence.

Immune disease dialogue of chemokine-based cell communications as revealed by single-cell RNA sequencing meta-analysis.

Immune-mediated diseases are characterized by aberrant immune responses, posing significant challenges to global health. In both inflammatory and autoimmune diseases, dysregulated immune reactions mediated by tissue-residing immune and non-immune cells precipitate chronic inflammation and tissue damage that is amplified by peripheral immune cell extravasation into the tissue. Chemokine receptors are pivotal in orchestrating immune cell migration, yet deciphering the signaling code across cell types, diseases and tissues remains an open challenge.

Getting to the Core: Exploring the Embryonic Development from Notochord to Nucleus Pulposus.

The intervertebral disc (IVD) is the largest avascular organ of the human body and plays a fundamental role in providing the spine with its unique structural and biomechanical functions. The inner part of the IVD contains the nucleus pulposus (NP), a gel-like tissue characterized by a high content of type II collagen and proteoglycans, which is crucial for the disc's load-bearing and shock-absorbing properties. With aging and IVD degeneration (IDD), the NP gradually loses its physiological characteristics, leading to low back pain and additional sequelae.

Molecular subtypes explain lupus epigenomic heterogeneity unveiling new regulatory genetic risk variants.

The heterogeneity of systemic lupus erythematosus (SLE) can be explained by epigenetic alterations that disrupt transcriptional programs mediating environmental and genetic risk. This study evaluated the epigenetic contribution to SLE heterogeneity considering molecular and serological subtypes, genetics and transcriptional status, followed by drug target discovery. We performed a stratified epigenome-wide association studies of whole blood DNA methylation from 213 SLE patients and 221 controls.

GENIX enables comparative network analysis of single-cell RNA sequencing to reveal signatures of therapeutic interventions.

Single-cell RNA sequencing (scRNA-seq) has transformed our understanding of cellular responses to perturbations such as therapeutic interventions and vaccines. Gene relevance to such perturbations is often assessed through differential expression analysis (DEA), which offers a one-dimensional view of the transcriptomic landscape. This method potentially overlooks genes with modest expression changes but profound downstream effects and is susceptible to false positives.

Genetic analyses of inflammatory polyneuropathy and chronic inflammatory demyelinating polyradiculoneuropathy identified candidate genes.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare, immune-mediated disorder in which an aberrant immune response causes demyelination and axonal damage of the peripheral nerves. Genetic contribution to CIDP is unclear and no genome-wide association study (GWAS) has been reported so far. In this study, we aimed to identify CIDP-related risk loci, genes, and pathways.

Novel biomarkers of preterm brain injury from blood transcriptome in sheep model of intrauterine asphyxia.

Background: Infants born preterm have a higher incidence of neurological deficits. A key step in finding effective treatments is to identify biomarkers that reliably predict outcome.

Methods: Following umbilical cord occlusion (UCO) in pregnant sheep, whole fetal blood RNA was sequenced pre- and post-UCO, brain injury outcome was determined by battery of neuropathology scoring and the transcriptome signature correlated to the degree of brain injury.

Scaling up single-cell RNA-seq data analysis with CellBridge workflow.

Summary: Single-cell RNA sequencing (scRNA-seq) has revolutionized the study of gene expression at the individual cell level, unraveling unprecedented insights into cellular heterogeneity. However, the analysis of scRNA-seq data remains a challenging and time-consuming task, often demanding advanced computational expertise, rendering it impractical for high-volume environments and applications. We present CellBridge, an automated workflow designed to simplify the standard procedures entailed in scRNA-seq data analysis, eliminating the need for specialized computational expertise.

Genome-wide association study analysis of disease severity in Acne reveals novel biological insights.

Acne vulgaris is a common skin disease that affects >85% of teenage young adults among which >8% develop severe lesions that leaves permanent scars. Genetic heritability studies of acne in twin cohorts have estimated that the heritability for acne is 80%. Previous genome-wide association studies (GWAS) have identified 50 genetic associated with increased risk of developing acne when compared to healthy individuals.

IL-33 Expression Is Lower in Current Smokers at both Transcriptomic and Protein Levels.

IL-33 is a proinflammatory cytokine thought to play a role in the pathogenesis of asthma and chronic obstructive pulmonary disease (COPD). A recent clinical trial using an anti-IL-33 antibody showed a reduction in exacerbation and improved lung function in ex-smokers but not current smokers with COPD. This study aimed to understand the effects of smoking status on IL-33.

A marker gene-based method for identifying the cell-type of origin from single-cell RNA sequencing data.

Single-cell RNA sequencing (scRNA-seq) experiments provide opportunities to peer into complex tissues at single-cell resolution. However, insightful biological interpretation of scRNA-seq data relies upon precise identification of cell types. The ability to identify the origin of a cell quickly and accurately will greatly improve downstream analyses.

DiSiR: fast and robust method to identify ligand-receptor interactions at subunit level from single-cell RNA-sequencing data.

Most cell-cell interactions and crosstalks are mediated by ligand-receptor interactions. The advent of single-cell RNA-sequencing (scRNA-seq) techniques has enabled characterizing tissue heterogeneity at single-cell level. In the past few years, several methods have been developed to study ligand-receptor interactions at cell type level using scRNA-seq data.

The integration of large-scale public data and network analysis uncovers molecular characteristics of psoriasis.

In recent years, a growing interest in the characterization of the molecular basis of psoriasis has been observed. However, despite the availability of a large amount of molecular data, many pathogenic mechanisms of psoriasis are still poorly understood. In this study, we performed an integrated analysis of 23 public transcriptomic datasets encompassing both lesional and uninvolved skin samples from psoriasis patients.

Vitiligo Skin T Cells Are Prone to Produce Type 1 and Type 2 Cytokines to Induce Melanocyte Dysfunction and Epidermal Inflammatory Response Through Jak Signaling.

Vitiligo is a T cell-mediated inflammatory skin disorder characterized by the loss of epidermal melanocytes. However, the contribution of melanocytes to the physiopathology of the disease in response to the T-cell microenvironment remains unclear. Here, using NanoString technology and multiplex ELISA, we show that active vitiligo perilesional skin is characterized by prominent type 1 and 2 associated immune responses.

The Th1 cell regulatory circuitry is largely conserved between human and mouse.

Gene expression programs controlled by lineage-determining transcription factors are often conserved between species. However, infectious diseases have exerted profound evolutionary pressure, and therefore the genes regulated by immune-specific transcription factors might be expected to exhibit greater divergence. T-bet (Tbx21) is the immune-specific, lineage-specifying transcription factor for T helper type I (Th1) immunity, which is fundamental for the immune response to intracellular pathogens but also underlies inflammatory diseases.

Publisher Correction: An optimized workflow for single-cell transcriptomics and repertoire profiling of purified lymphocytes from clinical samples.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

An optimized workflow for single-cell transcriptomics and repertoire profiling of purified lymphocytes from clinical samples.

Establishing clinically relevant single-cell (SC) transcriptomic workflows from cryopreserved tissue is essential to move this emerging immune monitoring technology from the bench to the bedside. Improper sample preparation leads to detrimental cascades, resulting in loss of precious time, money and finally compromised data. There is an urgent need to establish protocols specifically designed to overcome the inevitable variations in sample quality resulting from uncontrollable factors in a clinical setting.

Phase I/II open-label trial of intravenous allogeneic mesenchymal stromal cell therapy in adults with recessive dystrophic epidermolysis bullosa.

Background: Recessive dystrophic epidermolysis bullosa (RDEB) is a hereditary blistering disorder due to a lack of type VII collagen. At present, treatment is mainly supportive.

Objectives: To determine whether intravenous allogeneic bone marrow-derived mesenchymal stromal/stem cells (BM-MSCs) are safe in RDEB adults and if the cells improve wound healing and quality of life.

Interplay between the human gut microbiome and host metabolism.

The human gut is inhabited by a complex and metabolically active microbial ecosystem. While many studies focused on the effect of individual microbial taxa on human health, their overall metabolic potential has been under-explored. Using whole-metagenome shotgun sequencing data in 1,004 twins, we first observed that unrelated subjects share, on average, almost double the number of metabolic pathways (82%) than species (43%).