Colon or semicolon: gut sampling microdevices for omics insights.

Ingestible microdevices represent a breakthrough in non-invasive sampling of the human gastrointestinal (GI) tract. By capturing the native spatiotemporal microbiome and intricate biochemical gradients, these devices allow a non-invasive multi-omic access to the unperturbed host-microbiota crosstalk, immune/nutritional landscapes and gut-organ connections. We present the current progress of GI sampling microdevices towards personalized metabolism and fostering collaboration among clinicians, engineers, and data scientists.

Loss of synovial tissue macrophage homeostasis precedes rheumatoid arthritis clinical onset.

This study performed an in-depth investigation into the myeloid cellular landscape in the synovium of patients with rheumatoid arthritis (RA), "individuals at risk" of RA, and healthy controls (HC). Flow cytometric analysis demonstrated the presence of a CD40-expressing CD206CD163 macrophage population dominating the inflamed RA synovium, associated with disease activity and treatment response. In-depth RNA sequencing and metabolic analysis demonstrated that this macrophage population is transcriptionally distinct, displaying unique inflammatory and tissue-resident gene signatures, has a stable bioenergetic profile, and regulates stromal cell responses.

EnsembleSeq: a workflow towards real-time, rapid, and simultaneous multi-kingdom-amplicon sequencing for holistic and resource-effective microbiome research at scale.

Unlabelled: Bacterial communities are often concomitantly present with numerous microorganisms in the human body and other natural environments. Amplicon-based microbiome studies have generally paid skewed attention, that too at a rather shallow genus level resolution, to the highly abundant bacteriome, with interest now forking toward the other microorganisms, particularly fungi. Given the generally sparse abundance of other microbes in the total microbiome, simultaneous sequencing of amplicons targeting multiple microbial kingdoms could be possible even with full multiplexing.

Environmental insults and compensative responses: when microbiome meets cancer.

Tumor microenvironment has recently been ascribed a new hallmark-the polymorphic microbiome. Accumulating evidence regarding the tissue specific territories of tumor-microbiome have opened new and interesting avenues. A pertinent question is regarding the functional consequence of the interface between host-microbiome and cancer.

Transcriptomic profiling of programmed cell death 1 (PD-1) expressing T cells in early rheumatoid arthritis identifies a decreased CD4 + PD-1 + signature post-treatment.

Programmed cell death protein 1 (PD-1)-expressing T cells are expanded in individuals with established rheumatoid arthritis (RA). However, little is known about their functional role in the pathogenesis of early RA. To address this, we investigated the transcriptomic profiles of circulating CD4 and CD8 PD-1 lymphocytes from patients with early RA (n = 5) using fluorescence activated cell sorting in conjunction with total RNA sequencing.

Rheumatoid arthritis macrophages are primed for inflammation and display bioenergetic and functional alterations.

Objectives: Myeloid cells with a monocyte/macrophage phenotype are present in large numbers in the RA joint, significantly contributing to disease; however, distinct macrophage functions have yet to be elucidated. This study investigates the metabolic activity of infiltrating polarized macrophages and their impact on pro-inflammatory responses in RA.

Methods: CD14+ monocytes from RA and healthy control (HC) bloods were isolated and examined ex vivo or following differentiation into 'M1/M2' macrophages.

Differential expansion of T peripheral helper cells in early rheumatoid arthritis and osteoarthritis synovium.

Objectives: Programmed cell death protein 1 (PD-1)-expressing T cells are implicated in the pathogenesis of autoimmune inflammatory diseases such as rheumatoid arthritis. A subset of CXCR5 T cells, termed T peripheral helper (Tph) cells, which drive B cell differentiation, have been identified in ectopic lymphoid structures in established rheumatoid arthritis synovial tissue. Here, we aimed to characterise these in treatment-naïve, early rheumatoid arthritis to determine whether these cells accumulate prior to fully established disease.

Tracking mutational semantics of SARS-CoV-2 genomes.

Natural language processing (NLP) algorithms process linguistic data in order to discover the associated word semantics and develop models that can describe or even predict the latent meanings of the data. The applications of NLP become multi-fold while dealing with dynamic or temporally evolving datasets (e.g.

Distinct stromal and immune cell interactions shape the pathogenesis of rheumatoid and psoriatic arthritis.

Objectives: Immune and stromal cell communication is central in the pathogenesis of rheumatoid arthritis (RA) and psoriatic arthritis (PsA), however, the nature of these interactions in the synovial pathology of the two pathotypes can differ. Identifying immune-stromal cell crosstalk at the site of inflammation in RA and PsA is challenging. This study creates the first global transcriptomic analysis of the RA and PsA inflamed joint and investigates immune-stromal cell interactions in the pathogenesis of synovial inflammation.

Can machines learn the mutation signatures of SARS-CoV-2 and enable viral-genotype guided predictive prognosis?

Motivation: Continuous emergence of new variants through appearance/accumulation/disappearance of mutations is a hallmark of many viral diseases. SARS-CoV-2 variants have particularly exerted tremendous pressure on global healthcare system owing to their life threatening and debilitating implications. The sheer plurality of variants and huge scale of genomic data have added to the challenges of tracing the mutations/variants and their relationship to infection severity (if any).

Serologic Biomarkers of Progression Toward Diagnosis of Rheumatoid Arthritis in Active Component Military Personnel.

Objective: To identify a panel of serum biomarkers that could specifically identify imminent cases of rheumatoid arthritis (RA) before diagnosis.

Methods: Serum samples were collected at 4 time points from active component US military personnel, including 157 anti-citrullinated protein antibody (ACPA)-seropositive and 50 ACPA-seronegative RA subjects, 100 reactive arthritis (ReA) subjects, and 76 healthy controls. The cohorts were split into 2 phases, with samples tested on independent proteomic platforms for each phase.

MarkerML - Marker Feature Identification in Metagenomic Datasets Using Interpretable Machine Learning.

Identification of environment specific marker-features is one of the key objectives of many metagenomic studies. It aims to identify such features in microbiome datasets that may serve as markers of the contrasting or comparable states. Hypothesis testing and black-box machine learnt models which are conventionally used for identification of these features are generally not exhaustive, especially because they generally do-not provide any quantifiable relevance (context) of/between the identified features.

Attenuation of the BTLA/HVEM Regulatory Network in the Circulation in Primary Sjögren's Syndrome.

Primary Sjögren's syndrome (SjS) is an inflammatory autoimmune disorder which targets the lacrimal and salivary glands, resulting in glandular dysfunction. Currently, the immune drivers of SjS remain poorly understood and peripheral biomarkers of disease are lacking. The present study therefore sought to investigate the immune cell constituents of the SjS peripheral blood, and to assess the role of the BTLA/HVEM/CD160 co-stimulatory network by characterizing expression within the periphery.

Functionally Mature CD1c Dendritic Cells Preferentially Accumulate in the Inflammatory Arthritis Synovium.

Objective: To examine the role of synovial CD1cDCs in patients with Inflammatory Arthritis (IA) with a specific focus on the transcriptional and maturation signatures that govern their function.

Methods: RNA sequencing was performed on healthy control (HC) peripheral blood (PB), IA PB, and IA synovial fluid (SF) CD1cDCs. Multiparametric flow-cytometry and SPICE analysis were used to examine site [SF and Synovial Tissue (ST) CD1c+DCs] and disease specific characteristics of CD1cDCs, while functional assays such as antigen processing, activation, and MMP production were also performed.

ACPA Status Correlates with Differential Immune Profile in Patients with Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a progressive erosive autoimmune disease that affects 1% of the world population. Anti-citrullinated protein autoantibodies (ACPA) are routinely used for the diagnosis of RA, however 20-30% of patients are ACPA negative. ACPA status is a delineator of RA disease endotypes with similar clinical manifestation but potentially different pathophysiology.

Structural aspects of lesional and non-lesional skin microbiota reveal key community changes in leprosy patients from India.

Although skin is the primary affected organ in Leprosy, the role of the skin microbiome in its pathogenesis is not well understood. Recent reports have shown that skin of leprosy patients (LP) harbours perturbed microbiota which grants inflammation and disease progression. Herein, we present the results of nested Polymerase Chain Reaction-Denaturing Gradient Gel Electrophoresis (PCR-DGGE) which was initially performed for investigating the diversity of bacterial communities from lesional skin (LS) and non-lesional skin (NLS) sites of LP (n = 11).

Rheumatoid arthritis CD14 monocytes display metabolic and inflammatory dysfunction, a phenotype that precedes clinical manifestation of disease.

Introduction: This study investigates the metabolic activity of circulating monocytes and their impact on pro-inflammatory responses in RA and explores whether this phenotype is already primed for inflammation before clinical manifestations of disease.

Methods: Blood was collected and CD14 monocytes isolated from healthy control donors (HC), individuals at-risk (IAR) and RA patients. Monocyte frequency in blood and synovial tissue was assessed by flow cytometry.

Integration of the Transcriptome and Genome-Wide Landscape of BRD2 and BRD4 Binding Motifs Identifies Key Superenhancer Genes and Reveals the Mechanism of Bet Inhibitor Action in Rheumatoid Arthritis Synovial Fibroblasts.

Fibroblast-like synoviocytes (FLS), one of the main cell types of the rheumatoid arthritis (RA) synovium, possess phenotypic and molecular characteristics of transformed cells. JQ1, an inhibitor of the bromodomain and extra terminal domain family that includes BRD2, BRD3, BRD4, and BRDt, has shown efficacy in models of arthritis. We demonstrate that the active isomer of JQ1 but not its inactive isomer inhibits IL-1β-induced RA-FLS activation and proliferation.

Pathogenic, glycolytic PD-1+ B cells accumulate in the hypoxic RA joint.

While autoantibodies are used in the diagnosis of rheumatoid arthritis (RA), the function of B cells in the inflamed joint remains elusive. Extensive flow cytometric characterization and SPICE algorithm analyses of single-cell synovial tissue from patients with RA revealed the accumulation of switched and double-negative memory programmed death-1 receptor-expressing (PD-1-expressing) B cells at the site of inflammation. Accumulation of memory B cells was mediated by CXCR3, evident by the observed increase in CXCR3-expressing synovial B cells compared with the periphery, differential regulation by key synovial cytokines, and restricted B cell invasion demonstrated in response to CXCR3 blockade.

Correction to: NetConfer: a web application for comparative analysis of multiple biological networks.

An amendment to this paper has been published and can be accessed via the original article.

NetSets.js: a JavaScript framework for compositional assessment and comparison of biological networks through Venn-integrated network diagrams.

Motivation: Venn diagrams are frequently used to compare composition of datasets (e.g. datasets containing list of proteins and genes).

NetConfer: a web application for comparative analysis of multiple biological networks.

Background: Most biological experiments are inherently designed to compare changes or transitions of state between conditions of interest. The advancements in data intensive research have in particular elevated the need for resources and tools enabling comparative analysis of biological data. The complexity of biological systems and the interactions of their various components, such as genes, proteins, taxa, and metabolites, have been inferred, represented, and visualized via graph theory-based networks.

MetagenoNets: comprehensive inference and meta-insights for microbial correlation networks.

Microbial association networks are frequently used for understanding and comparing community dynamics from microbiome datasets. Inferring microbial correlations for such networks and obtaining meaningful biological insights, however, requires a lengthy data management workflow, choice of appropriate methods, statistical computations, followed by a different pipeline for suitably visualizing, reporting and comparing the associations. The complexity is further increased with the added dimension of multi-group 'meta-data' and 'inter-omic' functional profiles that are often associated with microbiome studies.

Discovery of -(Indazol-3-yl)piperidine-4-carboxylic Acids as RORγt Allosteric Inhibitors for Autoimmune Diseases.

The clinical success of anti-IL-17 monoclonal antibodies (i.e., Cosentyx and Taltz) has validated Th17 pathway modulation for the treatment of autoimmune diseases.

Cohort profile of a US military population for evaluating pre-disease and disease serological biomarkers in rheumatoid and reactive arthritis: Rationale, organization, design, and baseline characteristics.

Purpose: The etiology of several autoimmune disorders, including rheumatoid arthritis, remains unknown. While there are clear phases of disease progression, the mechanisms of transition between these phases are poorly understood. Additionally, treatment focuses on an alteration of the biological processes to prevent joint damage and functional decline.