Uncovering genetic diversity and admixture of British Africans with HLA alleles inferred from whole genome sequencing.

The human leukocyte antigen (HLA) region is highly diverse and plays a crucial role in immune regulation and antigen presentation. Accurate HLA typing is essential for understanding disease susceptibility, transplantation compatibility, and pharmacogenetics. However, its application in African descent populations is challenging due to complex linkage disequilibrium patterns and the lack of ancestry-matched populations in HLA reference panels.

Immune pathways and perinatal environmental exposures contribute to epigenetic gestational age prediction and acceleration.

DNA methylation (DNAm), capturing biological gestational age (GA) and epigenetic gestational age acceleration (EGAA), can be modified by environmental exposures. The Asthma&Allergy array is a new DNAm array developed with content focused on asthma and allergy loci. The association between content on the Asthma&Allergy array and chronological GA and EGAA has not been evaluated alone or in the context of perinatal exposures.

Structural basis of the inhibition of TRPV1 by analgesic sesquiterpenes.

The Transient Receptor Potential Vanilloid 1 (TRPV1) ion channel is expressed in primary nociceptive afferents, which participate in processes such as pain and inflammation. Considerable efforts have been directed toward finding inhibitors of TRPV1 and understanding the molecular details of their interactions with this channel. α-humulene (AH) is a sesquiterpene derived from plants such as hops and other members of Cannabaceae family, with a long history of popular use as an analgesic and anti-inflammatory.

Recently Evolved, Stage-Specific Genes Are Enriched at Life-Stage Transitions in Flies.

Understanding how genomic information is selectively utilized across different life stages is essential for deciphering the developmental and evolutionary strategies of metazoans. In holometabolous insects, the dynamic expression of genes enables distinct functional adaptations at embryonic, larval, pupal, and adult stages, likely contributing to their evolutionary success. While Drosophila melanogaster (D.

Diverse patterns of intra-host genetic diversity in chronically infected SARS-CoV-2 patients.

In rare individuals with a severely immunocompromised system, chronic infections of SARS-CoV-2 may develop, where the virus replicates in the body for months. Sequencing of some chronic infections has uncovered dramatic adaptive evolution and fixation of mutations reminiscent of lineage-defining mutations of variants of concern (VOCs). This has led to the prevailing hypothesis that VOCs emerged from chronic infections.

BugBuster: a novel automatic and reproducible workflow for metagenomic data analysis.

Summary: Metagenomic sequencing generates massive datasets that capture the complete genetic content of a sample, enabling detailed characterization of microbial communities. Yet the software and processes necessary to transform raw data into biologically meaningful results have become increasingly complex, limiting accessibility for researchers without specialist expertise. In this work, we present a novel modular a reproducible workflow developed to facilitate the analysis of metagenomic data.

Swiftly identifying strongly unique k-mers.

Motivation: Short DNA sequences of length k that appear in a single location (e.g., at a single genomic position, in a single species from a larger set of species, etc.

Cysteine pattern barcoding-based dataset filtration enhances the machine learning-assisted interpretation of Conus venom peptide therapeutics.

Crude cone snail venom is a rich source of bioactive compounds with significant therapeutic potential. In this study, we conducted a comprehensive analysis of 5,985 cone snail peptides across 82 Conus species to identify unique cysteine (Cys) patterns and associated frameworks. The classification of these Cys patterns, based on conserved framework combinations, enabled the generation of species-level pattern barcodes.

Single-Cell Analysis of Alternative Splicing and Gene Regulatory Network Reveals Remarkable Expression and Regulation Dynamics During Human Early Embryonic Development.

Single-cell RNA-seq (scRNA-seq) technologies greatly revolutionized our understanding of cell-to-cell variability of gene expression, but few scRNA-seq technologies were used to describe the expression dynamics at the isoform and exon levels. Although the current expression profile of early embryos was studied focusing on the expression changes at the gene level, systematic investigation of gene expression dynamics of human early embryonic development remains insufficient. Here we systematically explored the gene expression dynamics of human early embryonic development integrating gene expression level with alternative splicing, isoform switching, and expression regulatory network.

TriCLFF: a multi-modal feature fusion framework using contrastive learning for spatial domain identification.

Spatial transcriptomics (ST) encompasses rich multi-modal information related to cell state and organization. Precisely identifying spatial domains with consistent gene expression patterns and histological features is a critical task in ST analysis, which requires comprehensive integration of multi-modal information. Here, we propose TriCLFF, a contrastive learning-based multi-modal feature fusion framework, to effectively integrate spatial associations, gene expression levels, and histological features in a unified manner.

Identification of gut bacteria reductases that biotransform steroid hormones.

The metabolism of steroid hormones by the gut microbiome is increasingly recognized as a key factor in human health; however, the specific enzymes mediating these transformations remain largely unidentified. In this study, we identify Δ-3-ketosteroid 5β-reductase, 3β-hydroxysteroid dehydrogenase/Δ isomerase, and Δ-3-ketosteroid reductase enzyme families encoded by common human gut bacteria. Through phylogenetic reconstruction and mutagenesis, we show that 5β-reductase evolved to specialize in converting both natural and synthetic 3-ketosteroid hormones into their 5β-reduced derivatives, while Δ-3-ketosteroid reductase adapted to produce Δ-reduced derivatives.

Quantifying the intra- and inter-species community interactions in microbiomes by dynamic covariance mapping.

A microbiome's composition, stability, and response to perturbations are governed by its community interaction matrix, typically quantified through pairwise competition. However, in natural environments, microbes encounter multispecies interactions, complex conditions, and unculturable members. Moreover, evolutionary and ecological processes occur on overlapping timescales, making intra-species clonal diversity a critical but poorly understood factor influencing community interactions.

MicroRNAs regulate alveolar macrophage homeostasis and its function in lung fibrosis.

Introduction: Idiopathic pulmonary fibrosis is a progressive lung disease with a poor prognosis. Alveolar macrophages (AMs) are essential for maintaining lung homeostasis and play a significant role in the development of lung fibrosis. Tissue-Resident Alveolar Macrophages (TR-AMs), which originate from embryonic progenitors, can self-renew locally in a steady state, independent of hematopoiesis.

A patient-derived organoid model captures fetal-like plasticity in colorectal cancer.

Phenotypic plasticity is a hallmark feature driving cancer progression, metastasis, and therapy resistance. Fetal-like transcriptional programs have been increasingly implicated in promoting plastic cell states, yet their roles remain difficult to study due to limitations of existing culture models. Here, we establish a chemically defined patient-derived organoid system that enables long-term expansion of colorectal cancer (CRC) cells while preserving fetal-like features associated with phenotypic plasticity.

Genetic contributions to epigenetic-defined endotypes of allergic phenotypes in children.

Asthma is a common respiratory disease, with contributions from both genes and the environment and significant heterogeneity in underlying endotypes; yet, little is known about the relative contributions of each to these endotypes. To address this gap, we used nasal mucosal cell DNA methylation (DNAm) and gene expression and genotypes for 284 children in the Urban Environment and Childhood Asthma (URECA) birth cohort. Using an unbiased data-reduction approach and 37,256 CpGs on a custom-content Asthma&Allergy array, empirical Bayesian factorization was implemented to identify three DNAm signatures that were associated with phenotypes reflecting allergic diseases (allergic asthma and allergic rhinitis), allergic sensitization (atopy) (specific and total immunoglobulin E), and/or type 2 inflammation (eosinophil count and fractional exhaled nitric oxide [FeNO]).

Loss of stimulator of interferon genes (STING) promotes accumulation of cholesterol and triglycerides throughout life in mice.

Background: The Stimulator of Interferon Genes (STING) pathway is pivotal in innate immunity, facilitating the detection of cytosolic DNA and initiating type I interferon-dependent responses. In addition to its immunological roles, STING has been increasingly associated with metabolic regulation, since research indicates that its inhibition can diminish inflammation, lipid accumulation, and tissue damage in obesity and other metabolic disorders. The findings have prompted the suggestion of STING inhibition as a viable treatment approach for metabolic illness.

Evaluation of Small-Molecule Binding Site Prediction Methods on Membrane-Embedded Protein Interfaces.

Increasing structural and biophysical evidence suggests that many drug molecules bind to the protein-membrane interface region in membrane protein structures. An important starting point for drug discovery is the determination of a ligand's binding site; however, this information is missing for many membrane proteins, especially for their membrane-embedded parts. Therefore, we tested the performance of computational methods for ligand binding site prediction in the protein intramembrane region.

Yanomami skin microbiome complexity challenges prevailing concepts of healthy skin.

The adult skin microbiome typically exhibits low microbial complexity, particularly on sebaceous sites, where lipophilic Cutibacterium and Malassezia spp. predominate. Current understanding of healthy skin microbiome is largely based on western, industrialized populations, with limited representation of diverse cultures and lifestyles.

Gut microbial utilization of the alternative sweetener, D-allulose, via AlsE.

D-allulose, a rare sugar with emerging potential as a low-calorie sweetener, has garnered attention as an alternative to other commercially available alternative sweeteners, such as sugar alcohols, which often cause severe gastrointestinal discomfort. D-allulose-6-phosphate 3-epimerase (AlsE) is a prokaryotic enzyme that converts D-allulose-6-phosphate into D-fructose-6-phosphate, enabling its use as a carbon source. However, the taxonomic breadth of AlsE across gut bacteria remains poorly understood, hindering insights into the utilization of D-allulose by microbial communities.

Molecular insights into pangenome localization and constructs design for Hemophilus influenza vaccine.

Haemophilus influenza, a major contributor to respiratory infections such as pneumonia, meningitis, sinusitis, chronic bronchitis, and acute otitis, poses a significant public health challenge, driven by rising antibiotic resistance particularly among the non-typeable H. influenza (NTHi) strains given their ability to evade immune surveillance. To address this, we employed a comprehensive immunoinformatics pipeline integrated with extensive pan-genome analysis of 59 strains of H.

Histone serotonylation promotes pancreatic cancer development via lipid metabolism remodeling.

Neurotransmitter serotonin (5-hydroxytryptamine [5-HT]) has emerged to play parallel roles in both neurobiology and oncology. Apart from receptor-mediated signaling transduction pattern, serotonin can be covalently integrated into histone (the post-translational modification known as histone serotonylation) and serve as an epigenetic mark associated with permissive gene expression. However, how histone serotonylation influences tumorigenesis is yet to be understood.

The British-Israeli Project for Algorithm-Based Management of Age-Related Macular Degeneration: Deep Learning Integration for Real-World Data Management and Analysis.

Introduction: The aim of this study was to describe the development of an integrative dataset, combining clinical and optical coherence tomography (OCT) imaging data by applying a deep learning (DL) algorithm for automated, objective, and comprehensive quantification of OCT scans in two large real-world datasets of eyes with neovascular age-related macular degeneration (nAMD). We further report baseline characteristics of the study population, focusing on demographics, clinical parameters, and quantitative retinal morphological features.

Methods: This retrospective study analyzed data from 5,207 eyes of 4,265 nAMD patients treated at two centers in the UK and Israel.

Functional analysis of CYP4B1 enzymes from apes and humans uncovers evolutionary hot spots for adaptations of the catalytical function.

A hallmark of the highly conserved CYP4B1 enzyme in mammals is the capability to bioactivate both xenobiotic and endobiotic substrates. However, due to a single amino acid change (p.P427S) within the evolutionary conserved meander region no catalytic activity of the native human CYP4B1 has been identified so far.

Clonal Hematopoiesis of Indeterminate Potential Associated with Covert Cerebral Changes.

Objective: Clonal hematopoiesis of indeterminate potential (CHIP) is an emerging risk factor for cardio-cerebrovascular diseases. This study aimed to investigate CHIP's association with cerebrovascular or glymphatic changes in a community-based population.

Methods: This study examined Chinese community cohort participants.

DicePlot: A package for high dimensional categorical data visualization.

Summary: Visualization of multidimensional, categorical data is a common challenge across scientific domains and, in particular, the life sciences. The goal is to create a comprehensive overview of the underlying data which enables one to assess multiple variables. One application where such visualizations are particularly useful is gene or pathway analysis, which involves checking for dysregulation in known biological mechanisms and functions across multiple conditions.