DNA

A correlation between karyotype diversity and species richness was first observed in mammals in 1980 and subsequently confirmed after controlling for phylogenetic signal. The correlation was attributed to sub-microscopic factors, presumably operating at the level of the nucleus. The identities of these factors, however, remain unknown. Moreover, evidence demonstrating that they play any role in determining a relationship between karyotype diversity and species richness either in mammals or more generally in vertebrates is lacking. Species richness is commonly believed to be the result of diversifying selection occurring during adaptive radiation. Karyotypes, however, appear to evolve neutrally with selection acting primarily but not exclusively on genetic diversity. In 1991, Motoo Kimura proposed a molecular theory of non-adaptive radiation (NAR). Accordingly, genetic drift plays a significant role in speciation, albeit in parallel to and in conjunction with natural selection, suggesting that the nearly neutral evolution of karyotypes might participate in evolutionary dynamics during non-adaptive phases of adaptive radiations. The following will examine the contribution of DNA repair factors to the relationship between species richness and karyotype diversity and, by extension, to the large variation in species richness across the mammalian Tree of Life. Significance: As an integral part of the eukaryote DNA replication timing program (RT), DNA damage detection and repair systems (DDRs), including cell-cycle checkpoint systems and DNA double-strand break (DSB) repair pathways, organize the DNA synthetic phase (S phase) of the cell cycle and serve to coordinate genome duplication with mitosis and cell division. This review examines the role the DDR plays in sustaining and constraining mutation/substitution balance and the corresponding levels of genetic and genomic diversity on which natural selection operates. The efficiency and strength of the DDR, therefore, have important implications not only for genome stability but also for the evolution of genome architecture, karyotype diversity and, potentially, species richness. Many studies have been devoted to the role the DDR plays in cancer prevention and the evolution of body size and lifespan (K vs. r-strategists), but few studies have directly examined the role the DDR plays in speciation and adaptive radiations. Full article

Background/Objectives: The Mediterranean Sea is highly susceptible to marine bioinvasions, with non-indigenous ascidians frequently introduced and dispersed via maritime traffic. Here, we report the first records of the non-indigenous ascidian Polyclinum constellatum Savigny, 1816 in Maltese waters, identified within Marsaxlokk Harbour, which hosts a major international transshipment hub in the Central Mediterranean. Situated at a crossroads of global shipping lanes, Malta serves as a critical geographic sentinel for monitoring the occurrence and spread of non-indigenous species within the basin. Methods: Two colonies of P. constellatum were collected in 2022 and 2023 respectively. Given the condition of the sampled colonies, the high morphological plasticity and cryptic diversity within the genus Polyclinum Savigny, 1816, species identification was established using molecular taxonomy through DNA barcoding against reference sequences. Results: The obtained sequences from the two colonies were identical and confirmed the species’ identity through a 100% match in GenBank and BOLD. Comparative analysis revealed that the 678 bp sequences obtained here differed by 1 bp from previously documented Mediterranean records while matching others from more distant locations. The structure of the haplotype network based on the homologous sequences, together with the occurrence of multiple mitochondrial haplotypes across the Mediterranean Sea that are shared with geographically distant regions rather than neighbouring Mediterranean localities, supports a scenario involving multiple introductions of P. constellatum into the region, likely associated with maritime transport. Conclusions: These findings highlight the importance of integrating genetic markers into biosecurity monitoring frameworks to resolve taxonomic identities of cryptic taxa, improve understanding of invasion pathways and assess genetic diversity associated with the establishment and spread of non-indigenous species in novel environments. Full article

Antibiotic exposure promotes the emergence of antimicrobial resistance by activating SOS-dependent mutagenesis and facilitating horizontal gene transfer (HGT), both of which accelerate bacterial adaptation under selective pressure. Consequently, pharmacological inhibition of the SOS response has emerged as a promising strategy to suppress resistance evolution and enhance the efficacy of existing antibiotics. In particular, proteins involved in homologous recombination and DNA repair, such as RecA and LexA, represent attractive therapeutic targets for preventing SOS activation and limiting mutagenesis. This review highlights the pivotal role of the bacterial SOS response in antimicrobial resistance and discusses emerging strategies to therapeutically target the SOS pathway for combating resistant pathogens. Full article

Background: Oral leukoplakia is a clinically important oral potentially malignant disorder with variable risk of progression to oral squamous cell carcinoma. Histopathological grading of oral epithelial dysplasia remains the primary method for risk assessment; however, its predictive accuracy is limited by sampling variability, lesion heterogeneity, and interobserver variation. DNA aneuploidy and abnormal DNA ploidy status have therefore been investigated as objective biomarkers of genomic instability and potential predictors of malignant transformation. Aim: This narrative review evaluates whether DNA aneuploidy or abnormal DNA ploidy status predicts malignant transformation of oral leukoplakia to oral squamous cell carcinoma compared with diploid DNA status, and whether DNA ploidy should be interpreted as a stand-alone prognostic marker or as part of combined risk-assessment models. Materials and Methods: A structured PubMed/MEDLINE search (last performed on 12 July 2026) identified 162 records using terms related to oral leukoplakia, oral potentially malignant disorders, DNA ploidy, DNA aneuploidy, cytometry, malignant transformation, and oral squamous cell carcinoma. After screening and full-text eligibility assessment, 45 studies were included and organised according to their evidential role as core prognostic studies, PVL-specific subgroup evidence, and supporting/background evidence addressing diagnostic relevance, dysplasia correlation, treatment monitoring, genomic instability, and methodological development. Results: Most core prognostic studies showed that DNA aneuploidy, abnormal DNA content, or chromosomal instability was associated with increased malignant transformation risk compared with diploid or non-aneuploid status. Several studies reported higher transformation rates, hazard ratios, or improved prediction when DNA ploidy was combined with dysplasia grading, lesion site, clinical heterogeneity, or other biomarkers. However, predictive performance varied across studies, and DNA ploidy alone often showed modest sensitivity, specificity, or positive predictive value. Diploid or non-aneuploid status appeared more useful for identifying lower-risk lesions, although it did not completely exclude malignant transformation. PVL evidence suggested frequent aneuploidy and aggressive genomic behaviour, but DNA ploidy appeared less reliable for discriminating risk within PVL. Conclusions: DNA aneuploidy and abnormal DNA ploidy status are meaningful markers of genomic instability and are associated with increased malignant transformation risk in oral leukoplakia. However, when used alone, DNA ploidy often shows only modest predictive performance, and prediction improves consistently when it is combined with dysplasia grading and other clinicopathological factors. Their strongest clinical value is therefore as adjunctive biomarkers within combined clinicopathological and molecular risk models, rather than as stand-alone replacements for histopathological assessment; routine clinical implementation is not yet supported by the current evidence. Full article

Background/Objectives: Non-geniculate coralline red algae of the order Sporolithales are ecologically important calcium carbonate producers in tropical and subtropical seas globally; however, molecular surveys of this group in the Bay of Bengal (BoB) are entirely lacking, and no species of Sporolithon Heydrich has been documented from this embayment. Here we report the first occurrence of Sporolithon from Saint Martin Island, the sole coral island of Bangladesh, at the northernmost margin of the BoB. Methods: Seven specimens encompassing free-living rhodoliths to encrusting growth forms were collected from intertidal and shallow subtidal habitats in March 2024. Species identification was assessed by combining scanning electron microscopy (SEM) images with a six-locus molecular dataset comprising three plastid-encoded markers (rbcL, psbA, and UPA), the mitochondrial cytochrome c oxidase subunit I 5′ region (COI-5P), and two nuclear-encoded ribosomal markers (LSU and SSU). Results: Both maximum likelihood and Bayesian phylogenetic analyses resolved all BoB specimens within a well-supported clade of Sporolithon indopacificum Maneveldt, Gabrielson & Kangwe, with 0.00–0.20% concatenated rbcL + psbA sequence divergence from type specimens from Tanzania and previously published sequences from Fiji, China, and Guam (USA). SEM confirmed morpho-anatomical features concordant with the original species description, including a free-living rhodolith habit, monomerous construction, and tetrasporangial compartments with apical pore plugs. Conclusions: This record extends the confirmed range of S. indopacificum into the northeastern Indian Ocean, represents the first documented Sporolithon occurrence in Bangladeshi waters, and highlights the value of combining SEM with multi-locus barcoding for coralline algal surveys in undersampled tropical regions. Full article

Background/Objectives: Stingless bees (tribe Meliponini) are the most species-rich group of eusocial bees and critical pollinators across tropical ecosystems. Over the past seven decades, a growing number of studies have addressed their genetics and genomics, but coverage of the tribe remains taxonomically and geographically uneven. Here, we present a systematic evidence map and bibliometric science-mapping synthesis of this literature. Methods: We searched Scopus and Web of Science, retained 410 peer-reviewed articles published between 1950 and 2026, and applied structural topic modeling (STM) to characterize the thematic, temporal, taxonomic, and biogeographic structure of the corpus. Results: STM with K = 10 topics identified ten research themes, ranging from classical marker-based genetics and cytogenetics to phylogenomics, mitochondrial genomics, microbiome, and functional genomics. The estimated prevalence of phylogenomics/taxonomy and mitogenomics increased most steeply in recent years, a publication pattern consistent with—although not proof of—a shift toward genome-scale comparative approaches. Topic prevalence differed across biogeographic regions and subtribes: Neotropical and Meliponina-dominated studies were concentrated in population genetics, cytogenetics, and gene expression, whereas Indo-Australasian and Hypotrigonina-associated studies showed higher relative representation of DNA barcoding, mitogenomics, and microbiome research. Taxonomic representation was strongly skewed toward a few genera, with Melipona alone accounting for 43% of the corpus and most lineages across the Meliponini phylogeny remaining poorly studied. Conclusions: The principal contribution is a reproducible quantitative map of publication patterns; proposed research and conservation priorities are evidence-informed interpretations rather than direct outputs of STM. Full article

Pharmacogenomics can convert stable DNA variation into prescribing information, but its value in primary care depends on whether a result changes a decision at the right moment. This narrative review critically examines selected actionable gene–drug pairs, implementation models, conflicting evidence, and unresolved questions for family physicians managing multimorbidity and polypharmacy. A targeted search of PubMed/MEDLINE and current pharmacogenomic guideline resources was updated through 14 August 2026, prioritizing clinical guidelines, randomized and pragmatic trials, implementation studies, and primary-care evidence. Guideline actionability describes how an available result can guide treatment; it does not by itself establish that testing should be ordered. Selected examples include clopidogrel, statins, metoprolol, antidepressants, codeine and tramadol, proton-pump inhibitors, nonsteroidal anti-inflammatory drugs, and warfarin, together with shared-care medicines such as thiopurines and carbamazepine. In PREPARE, a defined 12-gene panel linked to prescribing recommendations reduced clinically relevant adverse drug reactions within a specific European workflow. Other trials showed that benefit is drug-, population-, comparator-, and workflow-dependent. Pharmacogenomics does not replace assessment of organ function, interactions, adherence, frailty, or patient preference. This review proposes selective, clinically triggered panel testing as a pragmatic model for primary care, with structured, reusable results and concise decision support. Future work should define who benefits, improve ancestry representation, account for phenoconversion, and demonstrate health-system-specific cost-effectiveness. Pharmacogenomics is best understood as an additional medication-safety input rather than a stand-alone precision-medicine solution. Full article

Sphingolipid metabolism has emerged as a regulatory interface between lipid homeostasis, organelle stress, and genome maintenance. Although sphingolipids are essential structural components of cellular membranes, specific metabolites also function as bioactive mediators that shape cellular responses to genotoxic stress. In this review, we examine how canonical and atypical sphingolipid pathways influence the DNA damage response through three mechanistic axes. First, ceramide-centered stress signaling links radiation, chemotherapy, and inflammatory injury to kinase and phosphatase pathways, mitochondrial apoptosis, and checkpoint-associated cell-fate decisions. Second, nuclear sphingolipid metabolism, particularly sphingosine kinase 2-dependent production of sphingosine-1-phosphate, regulates chromatin-associated transcriptional programs through modulation of histone deacetylase activity. Third, persistent sphingolipid imbalance promotes metabolic stress by disrupting lysosomal turnover, mitochondrial function, endoplasmic reticulum homeostasis, and redox balance, thereby increasing endogenous oxidative DNA damage. We also discuss atypical sphingolipids, including 1-deoxysphingolipids generated through altered serine palmitoyltransferase substrate utilization, as emerging mediators of mitochondrial dysfunction and genome instability. Finally, we consider the relevance of these mechanisms to cancer, lysosomal storage disorders, and neurodegenerative diseases, where sphingolipid dysregulation may influence therapeutic responses and disease progression. Together, these position sphingolipid metabolism as an integrated regulatory network connecting cellular stress signaling, chromatin regulation, organelle dysfunction, and genome stability. Full article

Background: Telomerase is a ribonucleic multimeric reverse transcriptase complex protecting the chromosomal ends from erosion and thereby from cellular senescence. The prognostic value of the components of this complex and their interrelationships with the immune system are not well understood. Objectives: We aimed to examine 15 telomerase-related genes across 7489 tumor samples from the TCGA database. Methods: The mRNA expression of these genes was analyzed using Kaplan–Meier statistics and hierarchical clustering analyses, alone or in combination with tumor infiltration counts for 11 immune cell types. As an additional analysis, univariable and multivariable Cox regression analyses have been performed. Results: Thirteen of 21 tumor types showed significant associations between gene expression in tumors and survival times of patients. Most gene correlations were found in hepatocellular carcinoma and renal clear cell carcinoma. In hepatocellular carcinoma, a high expression of DKC1, NHP2, GAR1, WRAP53, and ACD was associated with shorter survival. In renal clear cell carcinoma, TERT, DKC1, and PARN correlated with shorter survival, and NAF1, TERF2, POT1, and TINF2 with longer survival. DKC1 was the only gene significantly associated with poor prognosis in both tumor types. The telomerase-related genes correlated with patterns of immune cell infiltration, which influenced the survival of patients. The associations of mutation burden and neoantigen load with survival varied depending on the gene and patient groups. In renal clear cell carcinoma, TERT, DKC1, and PARN showed strong interactions with immune cell infiltration and neoantigen load. Conclusions: The combination of telomerase-related gene expression and immune-cell infiltration was associated with overall survival in hepatocellular carcinoma and renal clear cell carcinoma and warrants further evaluation as prognostic markers. Full article

Background/Objectives: Oxford Nanopore sequencing produces long reads quickly, but most functional profiling tools were developed for short reads or rely on assembly pipelines that are computationally costly and sensitive to long-read error rates. We present NanoPrism, a taxonomy-guided pipeline for rapid functional profiling of long-read metagenomes. Methods: NanoPrism (i) identifies sample composition with Kraken2, (ii) constructs compact species-specific coding sequence (CDS)–KEGG ortholog databases, and (iii) estimates ortholog abundances by direct minimap2 alignment of nanopore reads with single-copy marker normalization. We evaluated NanoPrism on simulated Pseudomonas aeruginosa PAO1 and PA14 reads and on ZymoBIOMICS mock-community datasets sequenced on GridION and PromethION platforms. Results: On the Zymo long-read datasets, NanoPrism achieved Pearson correlations of 0.917–0.922 against independent expected ortholog profiles under unit-sum normalization. On matched one-million-read subsets, NanoPrism achieved higher correlations and lower Jensen–Shannon distances and mean absolute errors than the evaluated DIAMOND-based MEGAN-LR workflow. Experiments that omitted one species at a time from the reference database showed that omission of low-abundance community members had limited effects on the aggregate KO profile, whereas omission of the dominant Listeria monocytogenes reference from the Log community reduced Pearson correlation from approximately 0.92 to 0.29. Conclusions: NanoPrism offers a computationally efficient option for taxonomy-guided functional profiling of bacterial isolates and defined microbial communities. Validation on complex clinical and environmental metagenomes, broader forms of taxonomic-classification error, and dedicated fungal benchmarks remain necessary. Full article

Background/Objectives: The PIM kinase family, comprising three serine/threonine kinase isoforms (PIM1, PIM2, and PIM3), plays a fundamental role in various cancer types, where they are frequently described as regulators of proliferation, survival, and metabolic pathways. Acute leukemia is a group of hematological malignancies characterized by the uncontrolled clonal proliferation of hematopoietic stem cells, encompassing myeloid (AML) and lymphoblastic (ALL) lineages, which together present limited therapeutic options and poor clinical outcomes. This study investigated the correlation between PIM kinase signaling pathways and the clinicopathological features, molecular pathway interactions, and cytogenetic risk stratification of patients with acute leukemia. Methods: Microarray data and clinical information from AML and ALL patients were retrieved from the Gene Expression Omnibus database. The expression levels of PIM1, PIM2, and PIM3 were assessed across leukemia subtypes and cytogenetic risk groups using ANOVA or Kruskal–Wallis tests, with Bonferroni post hoc correction, performed in R (v4.5.1). A transcriptome-wide co-expression analysis was conducted using Spearman’s rank correlation to identify genes correlated with each PIM isoform. Subsequently, Gene Set Enrichment Analysis (GSEA) was performed on pre-ranked gene lists using the clusterProfiler (v4.16.0) package and Hallmarks of Cancer gene signatures, with pathway significance determined by Benjamini–Hochberg-adjusted FDR < 0.05. Results: Transcriptomic analysis revealed distinct expression patterns of the PIM kinase family between AML and ALL subtypes, identifying PIM3 as the predominantly dysregulated isoform, marked by significant overexpression across both lineages. Risk-stratified analysis further demonstrated that PIM expression is highly context-dependent, exhibiting dynamic variation across cytogenetic risk groups. Functional enrichment analysis highlighted a potential functional redundancy and compensatory mechanisms among PIM isoforms, with enriched pathways predominantly associated with stress tolerance, hypoxia adaptation, and inflammatory signaling, rather than classical proliferative signatures. Conclusions: Collectively, these findings position the PIM kinase family as a dynamically regulated axis in acute leukemia, deeply integrated with cytogenetic risk profiles and stress-adaptation mechanisms. The consistent upregulation of PIM3 and its correlation with inflammatory and hypoxic signatures suggest a potential role in facilitating tumor survival within adverse microenvironments. Full article

Background/Objectives: The base excision repair (BER) pathway repairs oxidative DNA damage, a common and detrimental form of damage to the genome. Although biochemical steps in BER have been well defined, little is understood about how the pathway is regulated. Such regulation is critical, as cells must respond rapidly to DNA damage while avoiding aberrant activation of repair proteins that can produce DNA damage as intermediates in the repair pathway. Indeed, overexpression of the human BER protein NTHL1, a DNA N-glycosylase, can cause genomic instability and early cellular hallmarks of cancer. Methods: We developed a Saccharomyces cerevisiae model to explore how overexpression of NTHL1 may impair cellular function. Results: Overexpression of Ntg1, the budding yeast orthologue of NTHL1, impairs cell growth. To dissect mechanisms underlying this growth defect, we overexpressed either wild-type Ntg1 or a catalytically inactive variant of Ntg1 (ntg1_catdead). Consistent with results obtained for NTHL1, both variants of Ntg1 impair cell growth, but only the wild-type protein causes accumulation of double-strand breaks and chromosome loss. We screened a panel of DNA repair mutants for resistance/sensitivity to overexpression of wild-type Ntg1 or ntg1_catdead. This analysis identified several cellular pathways that protect cells from Ntg1-induced damage, providing insight into the interplay between DNA repair pathways. Finally, we identified a link to SUMOylation and probed into how this post-translational modification could contribute to regulation of Ntg1 function. Conclusions: This study describes a budding yeast system to understand how cells regulate and respond to dysregulation of the BER pathway. Full article

The migratory shad, Hilsa (Tenualosa ilisha) is an iconic species of profound economic and cultural value across the Indian sub-continent due to its delicious taste and significant contributions to gross domestic product (GDP). Lack of fundamental genomic data regarding sex determination, impedes development of optimized breeding techniques and target conservation goals. In this study, a next-generation sequencing (NGS)-based genotyping technique was applied to identify sex-linked markers, modes of sex determination, putative sex-determining genes and the population genomic structure of Hilsa. Genotyping of 94 Hilsa individuals (46 males and 48 females) collected from four distinct locations of Bangladesh (three different river systems and Bay of Bengal as a marine site) revealed 31,696 single-nucleotide polymorphisms (SNPs) and 12,754 presence/absence (PA) loci. Among these SNPs and PA, we identified 20 SNPs that were heterozygous in females but homozygous in males and 4 PA loci which were only present in females. Therefore, this study conclusively identifies a female heterogametic (ZZ/ZW) sex determination system in Hilsa. Comparative BLAST analysis using sex-linked loci against Hilsa genomes resulted in the identification of five candidate genes potentially involved in sex-determination pathways. Moreover, population genetic analysis revealed low spatial genetic differentiation among the four sampling sites but notable divergence between males and females (minimum 1.8–2.8% variation in principal coordinate analysis). For most of the sampling sites, higher observed heterozygosity (Ho) compared to expected heterozygosity (He) is the indicative of a robust population status with minimal evidence of inbreeding. Our study provides a baseline for further improving the management and conservation of the wild populations of the species. Full article

Background: The computation of DNA is a field of growing interest, primarily focused on studying its individual constituents, but a few authors have gone further by analyzing standard microhelices with DFT methods. Objective: Because these studies did not consider that, at the atomic level, other possible DNA and RNA helices with the WC-type arrangement are also stable, this is the main objective here. Methods: Therefore, forty microhelices were optimized in a simple model with three WC base pairs composed of nucleosides using the M06-2X DFT method. Results: Based on the spatial arrangement of the intramolecular H-bond with the 2′-OH group, five types of RNA:RNA double microhelices were obtained; by this arrangement, they were related to the corresponding DNA:DNA ones. In addition to A-type and B-type microhelices, two new types were found, conveniently named B1-type and C-type. The structural geometric parameters of all these optimized microhelices in an isolated state were compared and analyzed in detail. The total counterpoise-corrected interaction energies were determined in these microhelices. RNA microhelices with different types of intramolecular H-bond arrangements involving the 2′-OH group in each single strand were also optimized, as well as their corresponding DNA helices having the same spatial arrangement. Different DNA:RNA hybrid microhelices were also considered, and their structural geometric parameters were compared to those of other microhelices. Conclusions: the identification and detailed characterization, for the first time, of ten main stable spatial geometric shapes with different exocyclic and endocyclic torsional angles. Several relationships among the structural geometric parameters of these microhelices were also established. Although the new DNA/RNA helix types containing theoretically obtained WC pairs have not been found in biological helices, they could be synthesized and they may open the possibility of being used for other purposes. Full article

Background: Pulmonary aspergillosis remains underdiagnosed in patients with structural lung disease, as conventional methods might miss a part of cases. There are few real-world data on quantitative PCR performance outside immunocompromised populations. We evaluated the Aspergillus ELITe MGB Kit across two years of routine clinical practice at a tertiary pulmonology center. Methods: We retrospectively analyzed 492 consecutive ELITe MGB PCR tests (October 2023–September 2025) at the Marius Nasta Institute of Pneumology, Bucharest, Romania, performed on bronchoalveolar aspirate (n = 219), lavage (BAL; n = 202), and plasma (n = 65). Results were correlated with microscopy, fungal culture, imaging, and host risk factors where available. Results: Of 451 evaluable tests, 140 (31.0%) were significant, 7 (1.6%) low-level detected, and 304 (67.4%) non-significant or negative. Combined positivity was 32.6%. Aspirate outperformed BAL in positivity rate (42.8% vs. 30.8%; p ≈ 0.013); aspirate and BAL had similar median DNA loads (120 copies/mL each) but aspirate showed a longer tail toward very high loads (p < 0.001); raw median DNA loads (67 vs. 120 copies/mL) were not directly comparable between matrices due to differing matrix-specific lower limits of quantification (50 vs. 120 copies/mL, reflecting BAL dilution). Plasma positivity was 1.8%. Positivity peaked in May–June (42.5–45.5%), contrasting with the classical autumn pattern. Chronic obstructive pulmonary disease (COPD) was the dominant risk factor (OR = 3.45). PCR exclusively detected Aspergillus in the majority of cases where microscopy and culture were negative. Conclusions: The ELITe MGB kit demonstrates clinically meaningful diagnostic yield in a real-world pulmonology cohort. Aspirate consistently outperforms BAL, and the low-level detected category identifies a borderline population warranting prospective validation. The unexpected spring–summer positivity peak suggests a greater role for post-viral aspergillosis than previously recognized in this setting. Full article

Chronic respiratory diseases, including chronic obstructive pulmonary disease (COPD), asthma, and interstitial lung diseases (ILDs), represent a major global health burden. Their significant clinical and biological heterogeneity complicates diagnosis and limits the efficacy of traditional, one-size-fits-all management approaches. The advent of high-throughput genomic and multi-omic technologies has initiated a paradigm shift from syndromic classification to molecular-based endotyping. A narrative review of the literature was performed, synthesising foundational and recent research in the genomics, epigenomics, and multi-omics of chronic respiratory diseases. Key studies were selected based on their relevance to genetic architecture, biomarker development, and translational applications in precision medicine. We discuss the complex genetic architecture of pulmonary conditions, highlighting the contribution of both rare, high-penetrance variants, such as SERPINA1, CFTR, and BMPR2, and polygenic risk from many common variants, such as HHIP, FAM13A, and IL33. We provide detailed analyses of polygenic risk scores (PRSs) for COPD and asthma, including their construction, validation across ancestries, and predictive performance. We detail how integrative multi-omic approaches, including transcriptomics, proteomics, and metabolomics, are successfully defining molecular endotypes, such as Type 2-high asthma, which, in turn, inform the use of targeted biologic therapies. Finally, we review the development of molecular diagnostics, including metagenomic sequencing of infections and liquid biopsies for lung cancer and the development of prognostic biomarkers. The genomic revolution is transforming pulmonary medicine through the discovery of novel disease pathways, precise molecular classification, and the recognition of new therapeutic targets. Despite major challenges in functional interpretation, data integration, and clinical–translational equity, these technologies hold the key to a new era of personalised respiratory health and precision medicine. Full article

Background/Objectives: In recent years, efforts to understand obesity’s pathophysiology have focused on satiety signals in the hypothalamus and hormonal signalling in orexigenic and anorexigenic neurons. These signals, linked to hunger, satiety, and energy expenditure, are influenced by peptides that activate or suppress specific pathways. However, different phenotypes related to body composition result from mutations (allelic variants) in genes that encode these proteins, particularly peptide receptors. Specifically, the hormone receptor ghrelin (GHSR), located on the surface of orexigenic neurons, has been linked to the regulation of hunger. Additionally, the production and secretion of ghrelin, a peptide hormone produced by the stomach, may exhibit varying sensitivity in its receptor based on an individual’s nutritional status. Moreover, allelic variants of the GHSR gene may potentially lead to significant alterations in signalling provided by the GHSR receptor, resulting in modified hormone-binding phenotypes. In this context, the search for allelic variants that can account for diverse phenotypes, whether thinness or overweight/obesity, can aid in comprehending the pathway and defining new strategies for early laboratory diagnosis or target peptides for treatment. Methods: Initial mining produced 373 non-random SNPs located in missense regions. A total of 373 missense variants were initially identified in the GHSR gene. After applying a global minor allele frequency (MAF) filter of <1%, 20 rare missense variants remained. Results: These variants were subsequently analyzed using nine in silico pathogenicity prediction tools, resulting in the prioritization of eight variants predicted as deleterious by at least four algorithms. These variants were further analysed using the HOPE project web server and the SwissModel database. Conclusions: Through these analyses and future investigations into these mutations, we may gain a more comprehensive understanding of the implications of these mutations and their potential correlation with the pathophysiology of obesity. Full article

Eosinophilic esophagitis (EoE) and inflammatory bowel disease (IBD) are immune-mediated disorders of the gastrointestinal (GI) tract that, despite involving different tissues, are increasingly recognized to coexist. Epidemiologic studies demonstrate a bidirectional association, with patients affected by one condition showing a higher-than-expected prevalence of the other, suggesting shared susceptibility rather than incidental overlap. Genetic and epigenetic data support partial convergence in immune regulatory pathways, while epithelial barrier dysfunction and antigen-driven immune activation emerge as common upstream features. Overlapping cytokine networks, including IL-4, IL-13, and IL-23 signaling, contribute to chronic inflammation in both diseases, although differences in tissue environment and immune dominance give rise to distinct inflammatory phenotypes and clinical behavior. Clinical outcomes in patients with dual diagnoses appear heterogeneous, with available data suggesting neither uniformly worsened nor clearly protective disease courses, underscoring the complexity of shared immune mechanisms operating within different anatomic contexts. Beyond inflammatory activity, coexistence of EoE and IBD poses important nutritional and quality-of-life challenges, as overlapping dietary restrictions and chronic symptoms increase the risk of malnutrition, micronutrient deficiencies, and psychosocial burden. Current therapies remain disease-specific, with strong evidence supporting proton pump inhibitors, swallowed topical steroids, dietary therapy, and dupilumab in EoE, and biologics and small molecules targeting TNF-α, IL-12/23, IL-23, integrins, and JAK–STAT signaling in IBD, while evidence guiding treatment in patients with dual diagnosis remains limited. Together, current evidence supports a framework of shared immune machinery with tissue-specific expression that explains coexistence while preserving the distinct identities of EoE and IBD. By integrating emerging genetic, immunologic, and clinical evidence, this review aims to provide a framework for understanding and managing patients with coexisting EoE and IBD. Full article