Genomic Insights Research Articles

Black Hawaiian (BH) individuals, or Popolo, are a Native Hawaiian and Pacific Islander (NHPI) group characterized by significant African ancestry and a unique sociocultural history. Despite their distinct identity, BH individuals have been largely overlooked in genetic and biomedical research, with no prior studies in cardiovascular disease (CVD) that focus on treating BH as a unique population, rather than aggregating them with data from other NHPI subgroups (e.g., NHPI individuals of mixed European or Asian ancestry). Here, we present the first population genetic analysis of BH individuals, integrating ancestry deconvolution, demographic inference, and natural selection scans to elucidate their genetic profile and its potential cardiometabolic implications. We analyzed 287 BH whole-genome sequences from the NIH All of Us Research Program database and applied an ancestry deconvolution pipeline that included global ancestry inference (Neural ADMIXTURE) and local ancestry mapping (LAMP-LD). We reconstructed BH demographic history using the sequential Markovian coalescent model (smc++) and inferred a population-specific recombination map with recurrent learning for estimating recombination using neural networks (ReLERNN). To detect recent adaptation, we scanned BH genomes for signals of positive selection using integrated haplotype scores (iHS) and raised accuracy in sweep detection (RAiSD). Our results indicate that BH individuals form a genetically distinct cluster, separate from other admixed NHPI groups. However, they exhibit high internal genetic heterogeneity and lack clear population substructure, reflecting complex admixture sources and assimilation histories. We identified several candidate loci with notable allele frequency differentiation in BH genomes, featuring variants in genes associated with metabolic and cardiovascular traits such as lipid metabolism and inflammatory signaling pathways, some of which overlap with GWAS loci for CVD risk. This study provides the first genomic insights into BH groups and underscores the need for disaggregated genetic data in highly admixed populations such as those of Hawai'i to better understand and address CVD risk. Our findings establish a foundation for future genetic association studies involving BH individuals and have important implications for cardiometabolic disease mapping and precision medicine.

Background: Truncating variants in the TTN gene (TTNtv) are the most common genetic cause of non-ischemic (dilated) cardiomyopathy (CM) and are implicated in atrial fibrillation (AF). Frequently, AF is a sequela of CM; however, tachycardia-mediated cardiomyopathy (TMC) is an increasingly recognized clinical entity in which systolic dysfunction follows AF, with worse comorbidity and mortality than standalone AF. Restoration of normal sinus rhythm frequently restores systolic function. However, risk factors for the development of TMC have yet to be identified, and the contribution of TTNtv is unknown. Objective: Quantify the association of TTNtv with TMC in a large, healthcare-seeking general population. Methods: Individuals in the MyCode Community Health Initiative with exome sequencing were retrospectively assessed for the presence of AF (ICD-9/10 codes or EKG finding) and/or a TTNtv in highly expressed exons (>90% spliced in; hiPSI). TMC was defined as the presence of ICD-9/10 codes for new diagnosis of non-ischemic CM 1 day to 6 months after diagnosis of paroxysmal or persistent AF. Firth’s bias-reduced logistic regression with 1000 bootstrap iterations was performed to assess association of AF, CM, and TMC with TTNtv presence, with adjustment for age, sex, and the first four principal components of ancestry. Results: Of 171k individuals in MyCode, 21,570 (12.6%; median age 77 [IQR 69—84]; 43% female) had documented AF and 857 individuals (0.5%) had a qualifying TTNtv, including 198 (0.9%) in the AF group (OR 2.2 [1.8—2.6]; p<0.001). Of these AF+TTNtv individuals, 16 (8.1%) had TMC, whereas of 21,372 with AF and no TTNtv, 1,212 (5.7%) had TMC. AF+TTNtv individuals had significantly higher odds of having TMC compared to non-carriers (2.0 [1.2—2.9]; p=0.014; Figure). Phenotype analysis as currently defined demonstrated a PPV of 0.25, NPV of 0.90 w/ observed accuracy of 0.57, sensitivity of 0.73 and specificity of 0.54. Conclusion: In a healthcare-seeking population with exome sequencing, among those with AF, TTNtv presence was associated with 2-fold higher odds of developing ICD code-based TMC, suggesting that for individuals with TTNtv and AF, prompt treatment may be of particular importance. TMC is a complex phenotype that is difficult to define in electronic health records, thus future work will include refinement of the defined phenotype to improve specificity.

Background: Peripheral arterial disease (PAD) is a major cause of morbidity and mortality, particularly in type 2 diabetes mellitus (T2DM). Current treatments for diabetic PAD patients have limited efficacy, necessitating novel therapeutic approaches. The GIPR and GLP1R pathways have emerged as potential targets. This study leverages genetic data from the Million Veteran Program (MVP) to investigate the roles of GIP, GIPR, and GLP1R in PAD pathogenesis. Methods: We analyzed 51,330 European ancestry PAD cases and 256,807 controls. Locus zoom plots assessed genetic associations at GIP, GIPR, and GLP1R loci. Fine mapping (SuSiE) identified credible SNPs at GIP/GIPR, and Mendelian randomization (MR) evaluated causal effects of glycemic traits (HbA1c, T2DM) on PAD. Colocalization analysis assessed shared genetic signals. Results: GIP was significantly associated with PAD (rs35895680, P = 1e-10), with fine mapping identifying it as the most likely causal SNP (PIP = 0.993). While GIPR was not genome-wide significant, fine mapping identified an eQTL variant (rs8105523) linked to decreased GIPR expression. Colocalization confirmed shared genetic signals between PAD and HbA1c (PP = 0.99). MR analysis linked decreased GIPR expression with increased PAD risk for HbA1c (OR = 2.88, P = 0.020) and T2DM (OR = 1.95, P = 0.040). Conclusion: These findings highlight the therapeutic potential of dual GLP1R/GIPR agonists like Tirzepatide in PAD, supporting further clinical trials to validate incretin-based therapies in diabetic PAD patients.

BackgroundSoil salinization threatens global rice production, driving the urgent need for salt-tolerant rice cultivars. Sea rice HD961, renowned for its exceptional salt tolerance, serves as an ideal model for elucidating molecular adaptations to salinity.ResultsIn this study, we generated a high-quality, chromosome-level genome assembly of HD961 using Nanopore long-read sequencing, Illumina short-read polishing, and Hi-C-based scaffolding, providing a robust foundation for translatomic analysis. To explore translational responses to salt stress, we integrated ribosome profiling (Ribo-seq) with the QEZ-seq protocol and RNA sequencing (RNA-seq) under 150 mM NaCl conditions. Our results reveal that salt stress selectively enhances translational efficiency (TE) in genes critical for ion homeostasis, antioxidant defense, and cell wall remodeling, enabling HD961 to maintain cellular balance under stress. Especially, eukaryotic translation initiation factor 2B (eIF2B) emerged as a key regulator, with its upregulation and the formation of stress-induced eIF2B-containing bodies indicating a novel mechanism to optimize protein synthesis. Additionally, ribosome footprint profiling revealed codon-specific modulation of A-site dwell times, with the GCG codon showing a particularly pronounced shift under salt stress, suggesting fine-tuned translational control that prioritizes stress-responsive proteins.ConclusionTogether, these findings highlight eIF2B-mediated translational regulation as central to HD961’s salt tolerance, offering valuable genomic and translatomic resources for breeding salt-tolerant rice and other crops.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12915-025-02440-3.

Efforts to recover endangered species often rely on restoring populations to their historical range, yet reestablishing lost genetic variation is challenging when the ancestral genetic landscape is poorly understood. The Pacific pocket mouse (Perognathus longimembris pacificus), a federally endangered heteromyid rodent, has been extirpated from most of its range in coastal southern California. Recovery efforts call for establishing new populations in their historic range through translocation, but the extent to which historical patterns of genetic variation can be recapitulated is unknown. To inform conservation planning, we sequenced whole genomes of historical samples, including individuals from populations that went extinct in the mid-1900's. Phylogenetic analyses revealed that mice from the southernmost extirpated population form a clade with a different subspecies, while populations to the north form a sister clade. These findings support morphological evidence calling for a taxonomic revision, which would modify the definition of the historic range and complicate the interpretation of suitable reintroduction sites. Despite this divergence, D-statistics and demographic models indicate historical gene flow among coastal populations, suggesting that alleles reintroduced to the southern coast may echo ancestral connectivity. Thus, management efforts should consider potential receiver sites that contain suitable habitat within this range as viable for population creation. These results highlight the value of historical genomics in guiding conservation decisions, particularly when taxonomic uncertainty, extirpation, and limited genetic diversity constrain modern management. Although historical baselines often cannot be restored, conservation strategies can leverage genomic insights to enhance future adaptive potential and long-term resilience of threatened species.

Comprehensive whole-genome analysis of Streptococcus infantarius strains from Moroccan farmhouse dairy products: Genomic insights into dairy adaptation, safety, and biotechnological potential.

Speciation continuum in non-model organisms: Revisiting the species-pair concept in lichens.

Introduction: Coronavirus Disease-2019 (COVID-19) vaccines are a crucial tool in controlling and ultimately ending the pandemic, complementing other preventive measures. India launched its vaccination campaign on January 16, 2021, initially using two vaccines that received emergency authorisation: Covaxin (BBV152) and Covishield (ChAdOx1 nCoV-19). The vaccination effort began with elderly individuals (60+ years) and frontline workers, eventually expanding to include various age groups. During this period, India faced a severe second wave of COVID19, marked by a notable rise in postvaccination breakthrough infections throughout 2021, driven by more transmissible and potentially more immune-evasive variants. To date, no study is available that details the rate of these breakthrough infections and the variants responsible in our region. Aim: To determine the rate of breakthrough infections in our region and identify which Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants are responsible for these infections. Materials and Methods: This cross-sectional study was conducted in a tertiary care hospital in Northern India over one year, from January 2021 to December 2021. Nasopharyngeal swabs from suspected COVID-19 patients were collected and subjected to Ribonucleic acid (RNA) extraction, followed by Reverse Transcription-Polymerase Chain Reaction (RTPCR) testing. The breakthrough infection rate was defined as infections occurring in individuals who were fully vaccinated with two standard doses of the AZD1222/Covishield vaccine. Genome sequencing was performed to identify the SARSCoV-2 variants responsible for postvaccination breakthrough infections. Data analysis was conducted using Microsoft Excel Software 16. Results: Between January 2021 and December 2021, 513,197 nasopharyngeal swabs were analysed, with a total of 32,952 (6.42%) samples testing positive for SARS-CoV-2 by RT-PCR. Out of these, 2,043 (6.2%) samples were from cases in which individuals had been vaccinated with two doses of the vaccine. Genome sequencing of 11 such samples revealed that eight of the patients were infected with the Delta variant (Pango Lineage: B.1.617.2). One sample showed the Eta variant (Lineage B.1.575) with the E484K mutation. Unfortunately, two samples could not be processed due to inadequate quality. Conclusion: A breakthrough infection rate of 6.2% was recorded, with the Delta variant (Pango Lineage: B.1.617.2) of SARS-CoV-2 being commonly associated with these infections. This study underscores the need for continued and rigorous genomic surveillance of emerging SARS-CoV-2 variants to assess their potential to evade immune responses.

Genomic insights and process optimization for comprehensive biovalorization of lignocellulosic waste with microbial consortium

Advancing approaches to cultivate industrially and ecologically relevant microorganisms from termite guts.

ABSTRACTBrucella abortus S19 is a widely used live attenuated vaccine strain for bovine brucellosis control; however, its long‐term efficacy is challenged by genomic plasticity and adaptive mechanisms. This study presents a comprehensive comparative genomic and immunoinformatics analysis of a field strain (B. abortus S19, BAS19) isolated from an aborted cattle placenta 3 years post‐vaccination in Erzurum, Turkey. Whole‐genome sequencing was performed using Oxford Nanopore Technology, followed by genome assembly, functional annotation and comparative analyses against the reference strain (B. abortus S19, BAR19). Genomic variations, including 1153 single nucleotide polymorphisms (SNPs), 120 insertions and 2501 deletions, were identified. Annotation revealed 772 hypothetical proteins in BAS19 compared to 604 in BAR19, with distinct differences in virulence‐associated genes. Immunoinformatics analysis of 95 outer membrane proteins (OMPs) indicated significant antigenic variation, with 47 proteins exhibiting epitope loss and 11 displaying novel epitope gains. Beta‐barrel structure prediction demonstrated a reduction in structural stability, with nine OMPs losing beta‐barrel motifs, potentially influencing host‐pathogen interactions. These findings highlight key genomic adaptations in BAS19 that may influence its immunogenic properties and vaccine efficacy. The results contribute to a deeper understanding of B. abortus genomic diversity, providing insights for the rational design of improved vaccines and therapeutics tailored to regional epidemiological needs.

Novel Enterococcus phage BUCT630: Isolation and genomic insights targeting drug-resistant Enterococcus faecium in vitro and in vivo.

Olfactory recognition and transduction mechanism in Small-tailed Han Sheep.

Genomic insights into Erwinia amylovora prophages: Diversity, defense strategies, and phage-host coevolution.

Heavy metals and metalloids are increasingly dispersed throughout different parts of the planet due to various human activities, leading to toxicity in living organisms. Bacterial cells have tremendous potential to bioaccumulate or degrade enzymatically toxic heavy metals and adsorb metal ions. This study was done to evaluate the growth kinetics, bioaccumulation and biosorption potential, metabolic profile, and chromate reductase activity of an indigenous forest soil bacterium, Bacillus tropicus RWS2. The bacterium was able to bioaccumulate 47.6 mg g−1 of Pb, 56.9 mg g−1 of Cr, and 37.8 mg g−1 of As(V) with a removal efficiency of 97.5%, 74.2% and 44.94%, respectively. The Pb and Cr biosorption potential of the dried cellular biomass of the bacterium was relatively high. The bacterium also depicted potential in reducing the toxic hexavalent chromate to the trivalent form. Whole genome sequencing and codon usage analysis were also performed. The bacterial genome was found to comprise about 23 genes associated with heavy metal tolerance. Codon usage bias analysis depicted a moderately biased genome, while natural selection was predominant in shaping the codon usage bias of the genes associated with conferring heavy metal resistance to multiple heavy metals. This study demonstrates RWS2 as a multi-metal resistant bacterium and the combined physiological, biochemical, and genomic features of RWS2 underscore its promise as a genetically adaptable and efficient bioremediation agent.

Foodborne illnesses associated with Bacillus cereus represent a persistent public health concern. In this study, we described the isolation and characterization of a novel bacteriophage, ΦBc24, from mud samples, which showed lytic activity against foodborne pathogen B. cereus. Transmission electron microscopy revealed that ΦBc24 exhibited a myovirus morphotype. Biological assays demonstrated that its narrow host range was restricted to B. cereus strains and efficient lytic activity, characterized by a latent period of 10 min and a burst size of 40 PFU per infected cell. The phage exhibited high physicochemical stability, tolerating pH values of 2–12, temperatures of 4–50 °C, salinity up to 1 M NaCl, and ultraviolet exposure, while effectively suppressing host bacterial growth for up to six hours. Whole-genome sequencing showed that phage ΦBc24 possessed a double-stranded DNA genome of 160,311 bp, with 39.48% GC content, and 269 predicted open reading frames (ORFs). Remarkably, 11 tRNA genes were identified, whereas no genes associated with lysogeny, virulence, or antimicrobial resistance were detected. Phylogenetic analysis suggested that ΦBc24 belongs to the genus Caeruleovirus, subfamily Bastillervirinae, family Herelleviridae. Taken together, these results highlight the biological robustness and genomic safety of ΦBc24, supporting its potential as a biocontrol candidate against the foodborne pathogen B. cereus.

Controlling agricultural insect pests primarily depends on chemical insecticides, which pose environmental and health risks. This study comprehensively characterizes Bacillus thuringiensis (Bt) strain T419 and explores its potential as an eco-friendly biopesticide. Morphological analysis revealed diverse crystal structures including bipyramidal, spherical, and cuboidal shapes, indicative of broad insecticidal activity. SDS-PAGE confirmed the presence of key proteins corresponding to Cry1 (~ 130kDa), Cry2 (~ 65kDa), and Vip3 (~ 88kDa), known for their efficacy against lepidopteran pests. PCR screening confirmed the presence of genes encoding these insecticidal proteins, such as cry1, cry1Ac, cry1Ab, cry2, cry2Aa, cry2Ab, and vip3A. Whole genome sequencing yielded a 6.4Mb draft genome with 6,962 protein-coding sequences, including 2,327 hypothetical proteins, suggesting significant potential for novel gene discovery. Notably, 14 plasmids were identified which likely harboring key insecticidal genes. Bioassays demonstrated T419's effectiveness against economically important lepidopteran pests such as Spodoptera frugiperda (LC50 value of 2.821µg/mL), Spodoptera litura (LC50 value of 1.569µg/mL), and Plutella xylostella (LC50 value of 0.363µg/mL). Genome annotation revealed Bt genome T419 possesses many insecticidal toxin proteins such as Cry1Aa18, Cry1Ab11, Cry1Ab14, Spp1Aa1, Mpp46Ab1, Cry1Ac5, Cry1Ia42, Cry2Aa9, Cry2Ab41, and Vip3Aa86. In addition, it also possesses various virulence factors, including InhA metalloproteases, phospholipase C, sphingomyelinase, and chitinase, elucidating T419's sophisticated pathogenic mechanisms. These findings suggest that the Bt strain T419 is a promising candidate for developing new biopesticide formulations, offering a potent combination of broad-spectrum insecticidal activity and genetic diversity.

Production of the neurotoxin domoic acid (DA) by benthic diatom Nitzschia navis-varingica poses considerable health and economic concerns. In this study, we employed whole genome sequencing and transcriptomic analyses of regionally distinct N. navis-varingica strains to unravel the genomic underpinnings of DA biosynthesis. Our analyses revealed sizable genomes-characterized by an abundance of repetitive elements and noncoding DNA-that exceed the size of any other pennate diatoms. Central to our findings is the discovery of an expanded domoic acid biosynthesis (dab) gene cluster, spanning over 60 kb and marked by a unique organization that includes core genes interspersed with additional genetic elements. Phylogenetic and syntenic comparisons indicate that transposition events may have driven the expansion and reorganization of this cluster. Biochemical assays validated that the kainoid synthase encoded by dabC catalyzes the formation of isodomoic acid B, thereby establishing a distinct chemotype in contrast to the DA profiles of planktonic diatoms. These results highlight the evolutionary trajectory of DA biosynthesis in diatoms and potential advantages conferred by genome expansion and enzyme diversification in dynamic marine environments.IMPORTANCEDomoic acid (DA) is a potent neurotoxin produced by marine micro- and macroalgae problematic to fisheries and toxic to humans and animals. Our study elucidates the molecular mechanisms underlying DA production in the widespread Western Pacific benthic diatom, Nitzschia navis-varingica. Genomic and biochemical insights add information to our understanding of the evolution of toxin production across diverse phyla and also fill a gap in the knowledge of secondary metabolism in marine diatoms. These findings provide a genetic framework for identifying toxin production and its impacts in the benthos of vulnerable, coastal ecosystems.

Staphylococcus aureus (S. aureus), a significant pathogen in both humans and livestock, has been a critical concern in poultry farming due to the rise in antibiotic resistance and zoonotic spillover. The study investigated the genetic diversity and antibiotic resistance profiles of S. aureus isolates collected from poultry farms in Haripur city of Khyber Pakhtunkhwa, Pakistan. A total of 317 samples including chicken nasal passages, cloacae, skin surfaces as well as chicken's feed and litter were collected from four poultry farms and eight slaughter houses. A total of 24 S. aureus isolates were obtained using standard microbiological procedures followed by whole genome sequencing (WGS). The WGS analysis revealed that majority of isolates belonged to sequence type (ST) ST291 (n = 18) and ST88 (n = 6). Furthermore, the genomic analysis identified the presence of various antibiotic resistance genes against several different antibiotic classes including β-lactams [blaZ], quinolones [gyrA_S84L, parC_S80F], fosfomycin [glpT-A100V, glpT_F3I], tetracycline, [tet(38), tet(K)], and erythromycin [erm(C)] as well as diverse range of virulence genes associated with adhesion [clfB, spa, ebp, sdrD, sdrF], biofilm formation [icaA, icaB, icaC, icaD, icaR, isdG], toxin production [geh, hlb, hlgA, hly/hla, lukF-PV, lukS-PV], and immune evasion [aur, coa, sak, sbi, scn]. All isolates possessed mobile genetic elements, including plasmids, insertion sequences, and prophages, suggesting the potential spread of virulence or antibiotic-resistance genes to bacterial populations. The study emphasizes the need for effective biosecurity measures and prudent antibiotic use in poultry farming to mitigate the risk of zoonotic transmission and public health threats.

BackgroundRare actinomycetes, particularly Gordoni spp., are emerging as critical sources of bioactive metabolites and opportunistic pathogens.ResultsIn this study, we isolated three novel Gordonia strains from soil samples and characterized their taxonomic status using a polyphasic taxonomic approach. Phylogenetic analysis of 16S rRNA genes and whole-genome comparisons indicated that strains CPCC 205333 T, CPCC 205515 T, and CPCC 206044 T represent three distinct novel species. The overall genome relatedness indices of average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) between these studied strains and their related type strains of the genus Gordonia were all below the established thresholds for species delineation, confirming the classification of these three as novel species, for which we propose the names Gordonia altitudinis sp. nov., Gordonia ligustrum sp. nov., and Gordonia pistacia sp. nov., respectively. Functional annotation revealed their ecological versatility, with Gordonia spp. contributing significantly to soil microbiome functionality through plant growth-promoting traits (e.g., nitrogen fixation, siderophore production) and biosynthetic gene clusters (BGCs), while also harboring virulence factors. Pan-genomic analysis of 225 Gordonia strains delineated an open gene pool (α = 0.82; 22% fluidity), reflecting adaptive plasticity. Core genomes were enriched in conserved metabolic pathways, whereas accessory and strain-specific genes showed niche-driven functional diversification, suggesting ecological specialization.ConclusionThese findings expand the genomic and functional understanding of Gordonia, highlighting its dual role in environmental resilience and pathogenicity, with potential applications in biotechnology and microbiome engineering.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12866-025-04362-0.