Biology subjects

Wang, Q.

Publications and source records attributed to Wang, Q..

At least 253 records · Page 14Linked to original sources

bioRxiv2024

Rapid enzymatic assay for antiretroviral drug monitoring using CRISPR-Cas12a enabled readout

Maintaining efficacy of human immunodeficiency virus (HIV) medications is challenging among children because of dosing difficulties, the limited number of approved drugs, and low rates of medication adherence. Drug level feedback (DLF) can support dose optimization and timely interventions to prevent treatment failure, but current tests are heavily instrumented and centralized. We developed the REverse-transcriptase ACTivity-crispR (REACTR) assay for rapid measurement of HIV drugs based on the extent of DNA synthesis by HIV reverse transcriptase. CRISPR-Cas enzymes bind to synthesized DNA, triggering collateral cleavage of quenched reporters and generating fluorescence. We measured azidothymidine triphosphate (AZT-TP), a key drug in pediatric HIV treatment, and investigated the impact of assay time and DNA template length on REACTRs sensitivity. REACTR selectively measured clinically relevant AZT-TP concentrations in the presence of genomic DNA and peripheral blood mononuclear cell lysate. REACTR has the potential to enable rapid point-of-care HIV DLF to improve pediatric HIV care.

bioengineering↗

bioRxiv2024

NEMF inhibits proliferation and migration of ovarian cancer cells by blocking the PI3K/mTOR pathway

Nuclear export mediator factor (NEMF) is considered to be a tumor suppressor in Drosophila. Based on the analysis of data from an online database, NEMF is downregulated in ovarian cancer. However, the mechanism underlying its expression has not been reported thus far.In this study, the immunohistochemistry results showed that the expression of NEMF may be related to patient age and tissue differentiation. In vitro experiments indicated that overexpression of NEMF may inhibit cell proliferation and migration by inhibiting the PI3K/mTOR signaling pathway, thereby blocking cell cycle progression and promoting apoptosis (P < 0.05).Therefore, we speculate that NEMF is a potential tumor suppressor gene. Targeting NEMF may be an innovative therapeutic approach for ovarian cancer. Summary blurbNEMF is downregulated in ovarian cancer and the mechanism underlying its expression has not been reported thus far.In vitro experiments indicated that overexpression of NEMF inhibit cell proliferation and migration by inhibiting the PI3K/mTOR signaling pathway,thereby blocking cell cycle progression.

cancer biology↗

bioRxiv2024

CD40 ligation-induced ERK activation promotes autophagy which leads to enhanced radiosensitivity in cervical carcinoma cells

CD40, a member of the tumor necrosis factor (TNF) receptor superfamily, plays an important role not only in the immune system, but also in tumor progression. CD40 ligation reportedly promotes autophagy in immune cells. However, the effects of CD40 ligation on autophagy and its mechanism in solid tumor cells are still unclear. In this study, we find that CD40 ligation promotes autophagosome formation, and consequently promotes autophagic flux in cervical cancer cells. Mechanically, this effect relies on that ERK contributes to CD40 ligation-induced ATG13 upregulation by p53. Furthermore, we demonstrates that CD40 ligation-induced autophagy increases the radiosensitivity of cervical cancer cells. Taken together, our results provide new evidence for involvement of the CD40 pathway in autophagy and radiotherapy in cervical cancer cells.

cell biology↗

bioRxiv2024

Oncogene-induced senescence and senescence-associated secretory phenotype (SASP) determine the efficacy of palbociclib in PIK3CA mutated colorectal cancer

Palbociclib is an excellent CDK4/6 inhibitor, but its clinical application is mainly limited to the treatment of advanced ER+/HR+ and HER2- breast cancer. Its efficacy in colorectal cancer (CRC) is evaluated in multiple trials and so far remains undetermined. We found that the PIK3CA-mutant CRC cells were insensitive to palbociclib treatment compared with the PIK3CA wild-type counterparts, and they were in an OIS (oncogene-induced senescence) state which was predisposed to a strong senescence-associated secretory phenotype (SASP) upon treatment. These senescent cells excessively secreted various SASP factors LCN2, and ultimately caused palbociclib-resistance via upregulation of EGFR in the non-senescent CRC cells. Importantly, a drug combination screen identified that erlotinib could synergize with palbociclib to overcome the SASP-induced resistance. Overall, we found that PIK3CA mutation-induced senescence compromised the efficacy of palbociclib treatment in CRC but co-targeting EGFR could minimize the OIS-associated side effects while preserving the beneficial effects.

cancer biology↗

bioRxiv2024

Antibody evasiveness of SARS-CoV-2 subvariants KP.3.1.1 and XEC

SARS-CoV-2 continues to evolve and spread around the world, and it remains critical to understand the functional consequences of mutations that lead to dominant viral variants. KP.3.1.1 is currently the most prevalent subvariant worldwide, while the recombinant subvariant XEC is exhibiting the fastest growth rate. Here we measured the in vitro neutralization of KP.3.1.1 and XEC by human sera, monoclonal antibodies, and soluble hACE2 receptor relative to their parental subvariants KP.3 and JN.1. KP.3.1.1 and XEC were slightly more resistant (1.3-1.6-fold) than KP.3 to serum neutralization, and the resultant antigenic map showed that the new subvariants are antigenically similar. Both also demonstrated greater resistance to neutralization by select monoclonal antibodies and soluble hACE2, all of which target the top of the viral spike. Our findings suggested that upward motion of the receptor-binding domain in spike is partially hindered by the N-terminal-domain mutations found KP.3.1.1 and XEC, thereby allowing these subvariants to better evade serum antibodies that target the viral spike when it is in the up position and thus having a growth advantage in the population.

microbiology↗

bioRxiv2024

PRC1 and CTCF-Mediated Transition from Poised to Active Chromatin Loops Drives Bivalent Gene Activation

Polycomb Repressive Complex 1 (PRC1) and CCCTC-binding factor (CTCF) are critical regulators of 3D chromatin architecture that influence cellular transcriptional programs. Spatial chromatin structures comprise conserved compartments, topologically associating domains (TADs), and dynamic, cell-type-specific chromatin loops. Although the role of CTCF in chromatin organization is well-known, the involvement of PRC1 is less understood. In this study, we identified an unexpected, essential role for the canonical Pcgf2-containing PRC1 complex (cPRC1.2), a known transcriptional repressor, in activating bivalent genes during differentiation. Our Hi-C analysis revealed that cPRC1.2 forms chromatin loops at bivalent promoters, rendering them silent yet poised for activation. Using mouse embryonic stem cells (ESCs) with CRISPR/Cas9-mediated gene editing, we found that the loss of Pcgf2, though not affecting the global level of H2AK119ub1, disrupts these cPRC1.2 loops in ESCs and impairs the transcriptional induction of crucial target genes necessary for neuronal differentiation. Furthermore, we identified CTCF enrichment at cPRC1.2 loop anchors and at Polycomb group (PcG) bodies, nuclear foci with concentrated PRC1 and its tethered chromatin domains, suggesting that PRC1 and CTCF cooperatively shape chromatin loop structures. Through virtual 4C and other genomic analyses, we discovered that establishing neuronal progenitor cell (NPC) identity involves a switch from cPRC1.2-mediated chromatin loops to CTCF-mediated active loops, enabling the expression of critical lineage-specific factors. This study uncovers a novel mechanism by which pre-formed PRC1 and CTCF loops at lineage-specific genes maintain a poised state for subsequent gene activation, advancing our understanding of the role of chromatin architecture in controlling cell fate transitions.

genomics↗

bioRxiv2024

Biological age prediction using a novel DNN model based on steroid metabolic pathways

Aging involves the progressive accumulation of cellular damage, leading to systemic decline and age-related diseases. Despite advances in medicine, accurately predicting Biological Age (BA) remains challenging due to the complexity of aging processes and the limitations of current models. This study introduces a novel method for predicting BA using a Deep Neural Network (DNN) based on steroid metabolic pathways. We analyzed 22 steroids from 148 serum samples of individuals aged 20 to 73, using 98 samples for model training and 50 for validation. Our model reflects the often-overlooked fact that aging heterogeneity expands over time and uncovers sex-specific variations in steroid interactions. This study identified key markers, including cortisol (COL), which underscore the role of stress-related and sex-specific steroids in aging. The resulting model establishes a biologically meaningful and robust framework for predicting BA across diverse datasets, supporting more targeted strategies in aging research and disease management.

bioinformatics↗

bioRxiv2024

Continuous sensorimotor transformation enhances robustness of neural dynamics to perturbation in macaque motor cortex

Neural activity in the motor cortex dynamically evolves to plan and generate movement. How motor cortex adapts to dynamic environments or perturbations remains to be fully explored. In this study, we investigated whether dynamic nature of targets in a reach task requires distinct preparatory dynamics in motor cortex and result in varying levels of robustness against disruptions. Two monkeys were trained to perform delayed center-out reaches either to a static target (static condition) or a rotating target that needed to be intercepted (moving condition). Despite nearly identical hand kinematics in both two conditions, responses to the perturbation of intracortical microstimulation (ICMS) differed. In the static condition, ICMS led to prolonged reaction times, particularly when delivered shortly before movement onset and at anterior sites in PMd, aligning with previous findings. Unexpectedly, ICMS reduced reaction times in the moving condition. Furthermore, neural firing rates differed between the static and the moving conditions, with population activity in the latter exhibiting more rapid changes post-perturbation. Spatio-temporal sensorimotor transformation dominated throughout the preparation in the moving condition, while the static condition showed less stable motor intention representation, particularly during the late delay period. An input-driven model replicated the differences in RT-prolonging effect by assuming distinct input control strategy for the static and the moving condition. These findings suggest that input from a moving target to motor cortex can counteract ICMS effects, enabling the motor network to generate appropriate commands more quickly. Lastly, we propose that ICMS may facilitate go cue recognition, providing a potential explanation for the shortened reaction times in the moving condition.

neuroscience↗

bioRxiv2024

OsMORF protein selectively promotes the dual-localized RNA editing factor OsPGL1 binding to its target RNA

Post-transcriptional RNA editing plays a key regulatory role and serves as a genetic information proofreading mechanism. In flowering plants, RNA editing typically involves the removal of amino groups from cytidine to produce uridine in both plastids and mitochondria. In our previous work, we identified OsPGL1 as a rare organelle editing factor that regulates both mitochondrial and chloroplast RNA in rice. This protein mediates RNA editing and is associated with several OsMORFs. We speculated that they may form editing complex to regulate editing events, but we are still unclear about the detailed mechanism between OsMORF proteins and OsPGL1, as well as their roles in target RNA recognition and binding. In this study, we found that three OsMORFs can significantly promote the binding of OsPGL1 to target RNA in vitro. Notably, OsMORF8 can promote OsPGL1 to form a homologous dimer, thereby enhancing RNA binding to a greater extent. The E and DYW motifs do not affect the role of MORF proteins in RNA editing events, ruling out the potential influence of these two special motifs. In addition, we predicted a series of supercomplex structures of OsPGL1, the OsPGL1-RNA ligand complex, the OsPGL1-OsMORF2-OsMORF8-OsMORF9 complex, and the OsPGL1-OsMORF2-OsMORF8-OsMORF9-RNA complex. We determined that the conformational changes and newly added positively charged surface caused by OsMORF on OsPGL1 are the main reasons for MORF to promote the binding of OsPGL1 to RNA. Based on some new discoveries, we have expanded the RNA editing complex model, which greatly enhances our understanding of plant RNA editing complexes. Short summaryPPRs and MORFs are two kinds of RNA editing factors, both can mediate organelle RNA editing, the difference between them is that PPR can directly bind target RNA, MORF does not directly bind RNA, but can independently or assist PPR in performing RNA editing. Function of MORF protein in post-transcriptional processing is not clear, our study verifies the function of MORFs in the process of PPR binding RNA through molecular biology. We also analyzed the interaction network between PPR-MORF-RNA from the perspective of structural biology.

plant biology↗

bioRxiv2024

Diverse ancestral representation improves genetic intolerance metrics

Rapidly expanding genomic databases have enabled the identification of regions in the human genome intolerant to variation and thus likely relevant to human disease. However, despite their unprecedented scale, these datasets remain constrained by limited ancestral diversity. Here, we systematically evaluate how genetic diversity impacts gene- and sub-genic intolerance metrics by analyzing whole-exome sequencing data from 460,551 UK Biobank participants and 125,748 gnomAD participants across diverse ancestral backgrounds. Through comprehensive analysis of randomly sampled datasets with varying ancestral compositions, we demonstrate that genetic diversity, rather than sample size alone, drives the performance of intolerance metrics in identifying functionally critical genes and genic sub-regions. Notably, scores trained on variation observed in African and Admixed American ancestral groups showed superior resolution in detecting neurodevelopmental disease risk genes and haploinsufficient genes compared to scores trained on variation observed in European ancestry cohorts. Most strikingly, the Missense Tolerance Ratio (MTR) trained on 43,000 multi-ancestry exomes demonstrated greater predictive power than when trained on a nearly 10-fold larger dataset of 440,000 non-Finnish European exomes, indicating that European ancestry-based scores are approaching saturation. These findings establish ancestral diversity as the fundamental determinant for advancing intolerance metrics and underscore the urgent scientific and ethical imperative for enhanced population representation in genomic resources to fully realize the potential of precision medicine and drug discovery.

genetics↗

bioRxiv2024

Defective Neurogenesis in Lowe Syndrome is Caused by Mitochondria Loss and Cilia-related Sonic Hedgehog Defects

Human brain development requires tight coordination of metabolic and signaling pathways. Lowe syndrome (LS) is a recessive X-linked disorder characterized by proximal tubular renal disease, congenital cataracts, glaucoma, and neurodevelopmental delays. While LS results from mutations in the OCRL gene, which encodes an inositol polyphosphate 5-phosphatase, the cellular mechanisms driving neuronal dysfunction remain poorly understood. In this study, using patient-derived iPSC neurons, an OCRL knockout mouse model, and an independent zebrafish OCRL-deficient model, we identified mitochondrial dysfunction as a conserved phenotype of OCRL loss across species. Collectively, our findings showed that OCRL deficiency leads to reduced mitochondrial activity, decreased mtDNA levels, reduced mitochondrial content (TOM20), and increased oxidative stress. We further showed that OCRL-deficient neural cells exhibited an altered balance of neuronal versus astrocytic differentiation, rather than a defect in neurogenesis. Additionally, we observed impaired Sonic Hedgehog (Shh) signaling and ciliary homeostasis. Thus, we propose that mitochondrial dysfunction-induced oxidative stress acts as a central mediator linking OCRL loss to altered cell fate and disrupted Shh signaling, providing a unifying framework for these phenotypes.

cell biology↗

bioRxiv2024

In vivo genome editing of human hematopoietic stem cells for treatment of blood disorders by mRNA delivery

Ex vivo autologous hematopoietic stem cells (HSCs) gene therapy provides promising new treatments for hematological disorders. However, current methods involve complex processes and chemotherapeutic conditioning, leading to limited accessibility for treatment and significant side effects. Here, we developed an antibody-free targeted lipid nanoparticles (LNPs) for mRNA delivery to HSCs in vivo, enabling efficient base editing of the HBG target in human HSCs to reactivate fetal hemoglobin in derived erythroid cells. Delivery of ABE8e/sgRNA mRNA with optimized structure LNPs achieves efficient in vivo base editing of HBG in transfusion-dependent {beta}-thalassemia (TDT) patients derived HSCs engrafted in immunodeficient NCG-X mice, showing restored globin chain balance in erythroid cells. Our research indicated that utilizing LNPs for delivery of genome editor achieves efficient editing of endogenous genes of human HSCs. Notably, this non-viral delivery system eliminates the need for harvesting or mobilizing HSCs, providing a potent and one-time treatment potential for blood disorders like sickle cell disease (SCD) and TDT. HighlightsO_LIAntibody-free targeted LNPs system achieves efficient mRNA delivery and base editing in human bone marrow cells including HSCs via one-time intravenous injection. C_LIO_LIDelivery of ABE8e/sgRNA mRNA with optimized LNPs achieves efficient in vivo base editing of HBG in TDT patients derived HSCs engrafted in immunodeficient NCG-X mice, showing restored globin chain balance in erythroid cells. C_LIO_LILNPs efficiently deliver gene editing system to the BM for in vivo editing of human HSCs, providing preclinical evidence for the next generation non-viral gene therapy for blood disorders. C_LI

bioengineering↗

bioRxiv2024

Stoichiometry of HIV-1 Envelope Glycoprotein Protomers with Changes That Stabilize or Destabilize the Pretriggered Conformation

During human immunodeficiency virus (HIV-1) entry into host cells, binding to the receptors, CD4 and CCR5/CXCR4, triggers conformational changes in the metastable envelope glycoprotein (Env) trimer ((gp120-gp41)3). CD4 binding induces Env to make transitions from its pretriggered conformation (PTC) to more "open" conformations that are sensitive to inhibition by antibodies, CD4-mimetic compounds (CD4mcs) and exposure to cold. Changes in functional membrane Envs have been identified that either stabilize or destabilize the PTC. Here, we investigate the stoichiometric requirements for the PTC-stabilizing and -destabilizing changes in the Env protomers. To this end, we generated viruses bearing Envs with mixed protomers exhibiting different degrees of PTC stability and determined the sensitivity of the viruses to cold (0{degrees}C) and, in some cases, to a CD4mc. The number of stabilized Env protomers required to achieve stabilization of the PTC was inversely related to the degree of PTC stabilization that resulted from the introduced Env change. For strongly stabilizing Env changes, modification of a single protomer was sufficient to achieve PTC stabilization; given adequate stability, the modified protomer can apparently constrain the conformation of the other two protomers to maintain the PTC. Weakly stabilizing Env changes needed to be present in all three protomers to achieve efficient stabilization of the PTC. In many cases, the PTC was disrupted when destabilizing changes were present in only a single protomer. These complementary results suggest that conformational symmetry among the protomers of the functional Env trimer is conducive to the integrity of the PTC. IMPORTANCEThe human immunodeficiency virus (HIV-1) envelope glycoprotein (Env) trimer consists of three protomers. In response to receptor binding, the flexible Env changes its conformation to mediate virus entry into host cells. The shape-shifting ability of Env also contributes to HIV-1s capacity to evade the host immune system. The pretriggered (State-1) conformation (PTC) of Env is an important target for virus entry inhibitors and host antibodies, but is unstable and therefore incompletely characterized. Changes in Env amino acids that either stabilize or destabilize the PTC have been identified. Here, we define how many Env protomers need to be modified by these changes to achieve stabilization or destabilization of the PTC. These results can guide the placement of changes in the HIV-1 Env protomers to control the movement of the Env trimer from the PTC, allowing better characterization of this elusive conformation and testing of its utility in vaccines.

microbiology↗

bioRxiv2024

Abl kinases regulate FGF signaling independent of Crk phosphorylation to prevent Peters anomaly

Peters anomaly, the most common cause of congenital corneal opacity, stems from corneal-lenticular adhesion. Despite numerous identified mutations, a cohesive molecular framework of the diseases etiology remains elusive. Here, we identified Abl kinases as pivotal regulators of FGF signaling, as genetic ablation of Abl kinases restores lens induction even in the absence of FGF signaling. Intriguingly, both Abl kinase deficiency and increased FGF-Ras activity result in Peters anomaly independent of ERK signaling, which can be rescued by allelic deletion of Abl substrate, Crk. However, contrary to the prevailing belief that Abl kinases regulate Crk proteins by direct phosphorylation, mutations at Abl kinase phosphorylation sites on Crk and CrkL did not yield any observable effects. Instead, our findings reveal that Abl kinases phosphorylate Ptpn12, which in turn inhibits p130Cas phosphorylation and Crk recruitment, crucial for Rho GTPases activation and cytoskeletal dynamics. Consequently, Abl kinase deficiency reduces actomyosin contractility within the lens vesicle and genetically interacts with RhoA inhibition. Conversely, Rac1 deletion mitigates Peters anomaly in models with aberrant FGF, Abl kinase and RhoA signaling. Our results demonstrate that Abl kinases regulate FGF signaling to balance RhoA and Rac1 activity via the Ptpn12-p130Cas pathway, suggesting that targeting tension-mediated lens vesicle separation could be a therapeutic strategy for Peters anomaly.

developmental biology↗

bioRxiv2024

Shc1 cooperates with Frs2 and Shp2 to recruit Grb2 in FGF-induced lens development

Fibroblast growth factor (FGF) signaling elicits multiple downstream pathways, most notably the Ras/MAPK cascade facilitated by the adaptor protein Grb2. However, the mechanism by which Grb2 is recruited to the FGF signaling complex remains unresolved. Here we showed that genetic ablation of FGF signaling prevented lens induction by disrupting transcriptional regulation and actin cytoskeletal arrangements, which could be reproduced by deleting the juxtamembrane region of the FGF receptor and rescued by Kras activation. Conversely, mutations affecting the Frs2-binding site on the FGF receptor or the deletion of Frs2 and Shp2 primarily impact later stages of lens vesicle development involving lens fiber cell differentiation. Our study further revealed that the loss of Grb2 abolished MAPK signaling, resulting in a profound arrest of lens development. However, removing Grb2s putative Shp2 dephosphorylation site (Y209) neither produced a detectable phenotype nor impaired MAPK signaling during lens development. Furthermore, the catalytically inactive Shp2 mutation (C459S) only modestly impaired FGF signaling, whereas replacing Shp2s C-terminal phosphorylation sites (Y542/Y580) previously implicated in Grb2 binding only caused placental defects, perinatal lethality, and reduced lacrimal gland branching without impacting lens development, suggesting that Shp2 only partially mediates Grb2 recruitment. In contrast, we observed that FGF signaling is required for the phosphorylation of the Grb2-binding sites on Shc1 and the deletion of Shc1 exacerbates the lens vesicle defect caused by Frs2 and Shp2 deletion. These findings establish Shc1 as a critical collaborator with Frs2 and Shp2 in targeting Grb2 during FGF signaling.

developmental biology↗

bioRxiv2024

The first near-complete genome assembly of pig: enabling more accurate genetic research

Pigs are crucial sources of meat and protein, valuable animal models, and potential donors for xenotransplantation. However, the existing reference genome for pigs is incomplete, with thousands of segments and missing centromeres and telomeres, which limits our understanding of the important traits in these genomic regions. To address this issue, we present a near complete genome assembly for the Jinhua pig (JH-T2T), constructed using PacBio HiFi and ONT long reads. This assembly includes all 18 autosomes and the X and Y sex chromosomes, with only six gaps. It features annotations of 46.90% repetitive sequences, 35 telomeres, 17 centromeres, and 23,924 high-confident genes. Compared to the Sscrofa11.1, JH-T2T closes nearly all gaps, extends sequences by 177 Mb, predicts more intact telomeres and centromeres, and gains 799 more genes and loses 114 genes. Moreover, it enhances the mapping rate for both Western and Chinese local pigs, outperforming Sscrofa11.1 as a reference genome. Additionally, this comprehensive genome assembly will facilitate large-scale variant detection and enable the exploration of genes associated with pig domestication, such as GPAM, CYP2C18, LY9, ITLN2, and CHIA. Our findings represent a significant advancement in pig genomics, providing a robust resource that enhances genetic research, breeding programs, and biomedical applications.

genomics↗

bioRxiv2024

Curative levels of endogenous gene replacement achieved in non-human primate liver using programmable genomic integration

The ability to efficiently place a large piece of DNA in a specific genomic location has been a goal for the gene therapy field since its inception; however, despite significant advances in gene editing technology, this had yet to be achieved. Here we describe two methods of programmable genomic integration (PGI) that overcome some of the limitations of current approaches. Using a combination of clinically validated delivery technologies (LNP, AAV), we demonstrate the ability to specifically integrate large (>2 kb) DNA sequences into endogenous introns in the liver of non-human primates (NHP). PGI was effective across multiple genomic locations and transgenes, and insertion led to expression from the endogenous promoter. PGI was highly efficient, achieving expression in >50% of liver cells after a single course of treatment, which would be curative for most monogenic recessive liver diseases. This is the first report of clinically curative level of gene insertion at endogenous loci in NHP.

bioengineering↗

bioRxiv2024

Diversity and characteristics of the oral microbiome influenced by race and ethnicity

Periodontitis disproportionately affects racial/ethnic populations. Besides social determinants contributing to disparities in periodontal health, variations of oral microbial communities may also be a key factor influencing oral immune responses. To characterize the oral microbiome from different racial/ethnic populations, we collected 161 dental plaque samples from African Americans (AAs), Caucasian Americans (CAs), and Hispanic Americans (HAs) with clinical gingival health or biofilm-induced gingivitis on an intact periodontium. Using metagenomic sequencing, we found significant difference in diversity and abundance of microbial taxa in the dental plaque samples from AA, CA, and HA groups and unique microbial species that can only be detected in a particular racial/ethnic group. Moreover, we revealed racial/ethnic associated variations in functional potential of the oral microbiome, showing that diversity and abundance of antibiotic resistant genes were greater in the oral microbiome of the AAs than those in CAs or HAs, and that the AAs exhibited higher levels of genes involving in modification of glycoconjugates, oligo- and polysaccharides. These findings indicate more complex and higher virulence potential oral microbiome in AA and HA populations, which likely contributes to higher prevalence of periodontitis in AAs and HAs. ImportanceRecognizing the variations in the oral microbiome among racial/ethnic populations offers insight into the microbial determinants contributing to oral health disparities. In the study presented here, we found a higher level of bleeding on probing (BOP), an indicator of tissue inflammatory response, in the AA group, which is correspondence with a more complex oral microbiome detected in this group. Our observations suggest that the variations of the oral microbiome associated with racial/ethnic backgrounds may directly relate to their virulence potential including their abilities to induce host immune responses and to resist antibiotic treatment. Therefore, these finding can be a stepping stone for developing precision medicine and personalized periodontal prevention/treatment and for reducing oral health disparities.

microbiology↗