Biology subjects

Han, M.

Publications and source records attributed to Han, M..

At least 73 records · Page 4Linked to original sources

bioRxiv2021

MSD2, an apoplastic Mn-SOD, contributes to root skotomorphogenic growth by modulating ROS distribution in Arabidopsis

Reactive oxygen species (ROS) play essential roles as a second messenger in various physiological processes in plants. Due to their oxidative nature, ROS can also be harmful. Thus, the generation and homeostasis of ROS are tightly controlled by multiple enzymes. Membrane-localized NADPH oxidases are well known to generate ROS during developmental and stress responses, but the metabolic pathways of the superoxide (O2{middle dot}-) generated by them in the apoplast are poorly understood, and the identity of the apoplastic superoxide dismutase (SOD) is unknown in Arabidopsis. Here, we show that a putative manganese SOD, MSD2 is secreted and possesses a SOD activity that can be inhibited by nitration at tyrosine 68. The expression of MSD2 in roots is light condition-dependent, suggesting that MSD2 may act on ROS metabolism in roots during the light-to-dark transition. Root architecture is governed by ROS distribution that exhibits opposite gradient of H2O2 and O2{middle dot}-, which is indeed altered in etiolated msd2 mutants and accompanied by changes in the onset of differentiation. These results provide a missing link in our understanding of ROS metabolism and suggest that MSD2 plays a role in root skotomorphogenesis by regulating ROS distribution, thereby playing a pivotal role in plant growth and development.

plant biology↗

bioRxiv2021

The Siberian wild apple, Malus baccata (L.) Borkh., is an additional contributor to the genomes of cultivated European and Chinese apples

It is crucial to understand domestication to unravel the evolutionary processes that shape the divergence of populations. Differences in life-history traits have probably led to marked differences in the mode and speed of evolution between trees and annuals, particularly the extent of crop-wild gene flow during domestication. Apple is an iconic tree and major fruit crop grown worldwide. The contribution of wild apple species to the genetic makeup of the cultivated apple genome remains a topic of intense investigations. We used population genomics in combination with SNPs to investigate the contributions of the two known wild apple relatives, Malus sylvestris and Malus sieversii, and a supposed contributor, Malus baccata, to European and Chinese rootstock and dessert genomes, with a focus on the extent of wild-crop gene flow during apple domestication. We showed that the European dessert and rootstock apples form a specific gene pool, whereas the Chinese dessert and rootstock apples were a mixture of three wild gene pools. Coalescent-based inferences and gene flow estimates indicated that M. baccata is an additional contributor to the genome of both European and Chinese cultivated apples through wild-to-crop introgressions. We also confirmed previous results on the contribution of M. sylvestris to the cultivated apple genome, and provided insights into the origin of the apple rootstock. This study further demonstrates the role of gene flow during apple domestication, as seen in other woody perennials, and show that domestication of the apple tree involved several wild apple species.

evolutionary biology↗

bioRxiv2021

Early megakaryocyte lineage-committed progenitors in adult mouse bone marrow

Hematopoietic stem cells (HSCs) have been considered to progressively lose their self-renewal and differentiation potentials prior to the commitment to each blood lineage. However, recent studies have suggested that megakaryocyte progenitors are generated at the level of HSCs. In this study, we newly identified early megakaryocyte lineage-committed progenitors (MgPs) in CD201-CD48- cells and CD48+ cells separated from the CD150+CD34-Kit+Sca-1+Lin- HSC population of the bone marrow in C57BL/6 mice. Single-cell transplantation and single-cell colony assay showed that MgPs, unlike platelet-biased HSCs, had little repopulating potential in vivo, but formed larger megakaryocyte colonies in vitro (on average eight megakaryocytes per colony) than did previously reported megakaryocyte progenitors (MkPs). Single-cell RNA-sequencing supported that these MgPs lie between HSCs and MkPs along the megakaryocyte differentiation pathway. Single-cell colony assay and single-cell RT-PCR analysis suggested the coexpression of CD41 and Pf4 is associated with megakaryocyte colony-forming activity. Single-cell colony assay of a small number of cells generated from single HSCs in culture suggested that MgPs are not direct progeny of HSCs. In this study, we propose a differentiation model in which HSCs give rise to MkPs through MgPs.

cell biology↗

bioRxiv2021

Photosensitized Electrospun Nanofibrous Filters for Capturing and Killing Airborne Coronaviruses under Visible Light Irradiation

To address the challenge of the airborne transmission of SARS-CoV-2, photosensitized electrospun nanofibrous membranes were fabricated to effectively capture and inactivate coronavirus aerosols. With an ultrafine fiber diameter ([~] 200 nm) and a small pore size ([~] 1.5 {micro}m), the optimized membranes caught 99.2% of the aerosols of the murine hepatitis virus A59 (MHV-A59), a coronavirus surrogate for SARS-CoV-2. In addition, rose bengal was used as the photosensitizer for the membranes because of its excellent reactivity in generating virucidal singlet oxygen, and the membranes rapidly inactivated 98.9% of MHV-A59 in virus-laden droplets only after 15 min irradiation of simulated reading light. Singlet oxygen damaged the virus genome and impaired virus binding to host cells, which elucidated the mechanism of disinfection at a molecular level. Membrane robustness was also evaluated, and no efficiency reduction for filtering MHV-A59 aerosols was observed after the membranes being exposed to both indoor light and sunlight for days. Nevertheless, sunlight exposure photobleached the membranes, reduced singlet oxygen production, and compromised the performance of disinfecting MHV-A59 in droplets. In contrast, the membranes after simulated indoor light exposure maintained their excellent disinfection performance. In summary, photosensitized electrospun nanofibrous membranes have been developed to capture and kill airborne environmental pathogens under ambient conditions, and they hold promise for broad applications as personal protective equipment and indoor air filters. SynopsisPhotosensitized electrospun nanofibrous filters with excellent capture-and-kill performance against coronaviruses were designed and implemented to prevent the airborne transmission of COVID-19. Table of Contents O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=103 SRC="FIGDIR/small/454404v1_ufig1.gif" ALT="Figure 1"> View larger version (39K): org.highwire.dtl.DTLVardef@171d6corg.highwire.dtl.DTLVardef@18caad5org.highwire.dtl.DTLVardef@23b902org.highwire.dtl.DTLVardef@14746e4_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2021

Directed yeast genome evolution by controlled introduction of trans-chromosomic structural variations

Naturally occurring structural variations (SVs) are a considerable source of genomic variation and can reshape chromosomes 3D architecture. The synthetic chromosome rearrangement and modification by loxP-mediated evolution (SCRaMbLE) system has been proved to generate random SVs to impact phenotypes and thus constitutes powerful drivers of directed genome evolution. However, how to reveal the molecular mechanism insights into the interactions between phenotypes and complex SVs, especially inversions and translocations, has so far remained challenging. In this study, we develop a SV-prone yeast strain by using SCRaMbLE with two synthetic chromosomes, synV and synX. An heterologous biosynthesis pathway allowing a high throughput screen for increased yield of astaxanthin is used as readout and a proof of concept for the application of SV in industry. We report here that complex SVs, including a pericentric inversion and a trans-chromosomes translocation between synV and synX, result in two neochromosomes and a 2.7-fold yield of astaxanthin. We demonstrated that inversion and inversion reshaped chromosomes 3D architecture and led to large reorganization of the genetic information nearby the breakpoint of the SVs along the chromosomes. Specifically, the pericentric inversion increased the expression of STE18 and the trans-chromosomic translocation increased the expression of RPS5 and MCM22, which contributed to higher astaxanthin yield. We also used the model learned from the aforementioned random screen and successfully harnessed the precise introduction of trans-chromosomes translocation and pericentric inversions by rational design. Overall, our work provides an effective tool to not only accelerate the directed genome evolution but also reveal mechanistic insight of complex SVs for altering phenotypes.

synthetic biology↗

bioRxiv2021

Multi-color super-resolution imaging to study human coronavirus RNA during cellular infection

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the third human coronavirus within 20 years that gave rise to a life-threatening disease and the first to reach pandemic spread. To make therapeutic headway against current and future coronaviruses, the biology of coronavirus RNA during infection must be precisely understood. Here, we present a robust and generalizable framework combining high-throughput confocal and super-resolution microscopy imaging to study coronavirus infection at the nanoscale. Employing the model human coronavirus HCoV-229E, we specifically labeled coronavirus genomic RNA (gRNA) and double-stranded RNA (dsRNA) via multicolor RNA-immunoFISH and visualized their localization patterns within the cell. The exquisite resolution of our approach uncovers a striking spatial organization of gRNA and dsRNA into three distinct structures and enables quantitative characterization of the status of the infection after antiviral drug treatment. Our approach provides a comprehensive framework that supports investigations of coronavirus fundamental biology and therapeutic effects.

cell biology↗

bioRxiv2021

Interrogation of the Dynamic Properties of Higher-Order Heterochromatin Using CRISPR/dCas9

Eukaryotic chromosomes feature large regions of compact, repressed heterochromatin hallmarked by Heterochromatin Protein 1 (HP1). HP1 proteins play multi-faceted roles in shaping heterochromatin, and in cells, HP1 tethering to individual gene promoters leads to epigenetic modifications and silencing. However, emergent properties of HP1 at supranucleosomal scales remain difficult to study in cells due to lack of appropriate tools. Here, we develop CRISPR-Engineered Chromatin Organization (EChO), combining live cell CRISPR imaging with inducible large-scale recruitment of chromatin proteins to native genomic targets. We demonstrate that human HP1 tiling across kilobase-scale genomic DNA forms novel contacts with natural heterochromatin, integrates two distantly targeted regions, and reversibly changes chromatin from a diffuse to compact state. The compact state exhibits delayed disassembly kinetics and represses transcription across over 600 kilobases. These findings support a polymer model of HP1-mediated chromatin regulation and highlight the utility of CRISPR-EChO in studying supranucleosomal chromatin organization in living cells.

genomics↗

bioRxiv2020

Gut microbiome couples gut and brain during calorie restriction in treating obesity

Calorie restriction (CR) has been widely recognized for its effect in reducing body weight and alleviating diabetes in humans, as well as prolonging life span in animal studies. Gut microbiome shifts contribute to part of the effects of CR, but little is known regarding their influences except on metabolism and immunity. Here we monitored gut microbiome using metagenomics and metatranscriptomics in obese individuals undergoing CR, and revealed microbial determinants that could contribute to successful weight loss. Microbiome changes are linked to changes in blood metabolome and hormones, which eventually correlate to brain functional changes as studied using functional magnetic resonance imaging (fMRI). Brain functional shifts indicate response of central neural system (CNS) to CR, and microbiome constitutes the keystone of gut-brain axis. Animal experiment further reaffirms the gut microbiome changes, metabolic and hormonal shifts of CR, while proteomic analysis of brain tissues suggest that epigenetic modifications of key proteins could explain responses of CNS to CR. Our study establishes linkage between CR, gut microbiome, metabolome/ hormones and CNS function, and demonstrates that CR has multi-facet, coordinated effects on the host, of which many could contribute to weight loss and other beneficial effects.

microbiology↗

bioRxiv2020

Transferrin receptor (Tfr1) ablation in satellite cells impacts skeletal muscle regeneration through the activation of ferroptosis

Satellite cells (SCs) are critical to the postnatal development and skeletal muscle regeneration. Inactivation of SCs is linked with the skeletal muscle loss. Leveraging on the RNAseq screening, transferrin receptor (Tfr1) is identified to be associated with muscle/SC ageing and the declined regeneration potential. Muscle-specific deletion of Tfr1 results in the growth retardation, metabolic disorder and lethality, shedding light on the importance of Tfr1 in skeletal muscle physiology. Here, our investigation reported that conditional SC-ablation of Tfr1 leads to the SCs inactivation and skeletal muscle regeneration defects, followed by the labile iron accumulation, de novo lipogenesis via fibroadipogenic progenitors (FAPs) and Gpx4/Nrf2-mediated ROS-scavenger defects. These abnormal phenomena, such as Hmox1-mediated myoglobin degradation, Tfr1-Slc39a14 functional switch and the activation of unsaturated fatty acid biosynthesis pathway are orchestrated with the occurrence of ferroptosis in skeletal muscle. Ferroptosis may further prevent SC proliferation and skeletal muscle regeneration. Ferrostatin-1, a ferroptosis inhibitor could not rescue Tfr1-ablation induced ferroptosis. However, intramuscular administration of lentivirus expressing Tfr1 could partially reduce labile iron accumulation, decrease de novo lipogenesis and promote skeletal muscle regeneration. Most importantly, Tfr1/Slc39a14 functional switch, labile iron accumulation and fatty acid biosynthesis are recapitulated in aged skeletal muscle of rodents, indicating that ferroptosis occurs in the skeletal muscles of aged rodents. The present study also bridges the gap between pathogenesis of iron and functional defects in the skeletal muscle, providing mechanistic information to develop anti-aging strategies. One Sentence SummaryConditional ablation of Tfr1 in satellite cells (SCs) results in the SC inactivation, skeletal muscle regeneration defects, labile iron accumulation, and unsaturated fatty acid biosynthesis, leading to the activation of ferroptosis, which is recapitulated in skeletal muscles of aged rodents to be a new cell death form identified in skeletal muscle and sheds light on the development of novel anti-ageing strategies.

cell biology↗

bioRxiv2020

An expanded gene catalog of mouse gut metagenome

High-quality and comprehensive reference gene catalogs are essential for metagenomic research. The rather low diversity of samples used to construct existing catalogs of mouse gut metagenomes limits the size and numbers of identified genes in existing catalogs. We therefore established an expanded gene catalog of genes in the mouse gut metagenomes (EMGC) containing >5.8 million genes by integrating 88 newly sequenced samples, 86 mouse-gut-related bacterial genomes and 3 existing gene catalogs. EMGC increases the number on non-redundant genes by more than one million genes compared to the so far most extensive catalog. More than 50% of the genes in EMGC were taxonomically assigned and 30% were functionally annotated. 902 Metagenomic species (MGS) assigned to 122 taxa are identified based on the EMGC. The EMGC-based analysis of samples from groups of mice originating from different animal providers, housing laboratories and genetic strains substantiated that diet is a major contributor to differences in composition and functional potential of the gut microbiota irrespective of differences in environment and genetic background. We envisage that EMGC will serve as an efficient and resource-saving reference dataset for future metagenomic studies in mice.

bioinformatics↗

bioRxiv2020

Distinct mechanisms for TMPRSS2 expression explain organ-specific inhibition of SARS-CoV-2 infection by enzalutamide

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly become a global public health threat due to the lack of effective drugs or vaccines against SARS-CoV-2. The efficacy of several repurposed drugs has been evaluated in clinical trials. Among these drugs, a relatively new antiandrogen agent, enzalutamide, was proposed because it reduces the expression of transmembrane serine protease 2 (TMPRSS2), a key component mediating SARS-CoV-2-driven entry into host cells, in prostate cancer cells. However, definitive evidence for the therapeutic efficacy of enzalutamide in COVID-19 is lacking. Here, we evaluated the antiviral efficacy of enzalutamide in prostate cancer cells, lung cancer cells, human lung organoids and SARS-CoV-2-infected Ad-ACE2-transduced Tmprss2 knockout (Tmprss2-KO) and wild-type (WT) mice. TMPRSS2 knockout significantly inhibited SARS-CoV-2 infection in vivo. Enzalutamide effectively inhibited SARS-CoV-2 infection in human prostate cancer cells (LNCaP) but not in human lung cancer cells or patient-derived lung organoids. Although Tmprss2 knockout effectively blocked SARS-CoV-2 infection in ACE2-transduced mice, enzalutamide showed no antiviral activity due to the AR independence of TMPRSS2 expression in mouse and human lung epithelial cells. Moreover, we observed distinct AR binding patterns between prostate cells and lung cells and a lack of direct binding of AR to TMPRSS2 in human lung cells. Thus, our findings do not support the postulated protective role of enzalutamide in treating COVID-19.

microbiology↗

bioRxiv2020

Efficient and stable metabarcoding sequencing from DNBSEQ-G400 sequencer examined by large fungal community analysis

ABSTRACTMetabarcoding has become the de facto method for characterizing the structure of microbial communities in complex environmental samples. To determine how sequencing platform may influence microbial community characterization, we present a large-scale comparison of two sequencing platforms; Illumina MiSeq and a new platform DNBSEQ-G400 developed by MGI Tech. The accuracy of DNBSEQ-G400 on bacterial and fungal mock samples and compared sequencing consistency and precision between DNBSEQ-G400 and MiSeq platforms by sequencing the fungal ITS2 region from 1144 soil samples with 3 technical replicates. The DNBSEQ-G400 showed a high accuracy in reproducing mock communities containing different proportions of bacteria and fungi, respectively. The taxonomic profiles of the 1144 soil samples generated by the two DNBSEQ-G400 modes closely resembled each other and were highly correlated with those generated by the MiSeq platform. Analyses of technical replicates demonstrated a run bias against certain taxa on the MiSeq but not DNBSEQ-G400 platform. Based on lower cost, greater capacity, and less bias, we conclude that DNBSEQ-G400 is an optimal platform for short-term metabarcoding of microbial communities.IMPORTANCE Experimental steps that generate sequencing bias during amplicon sequencing have been intensively evaluated, including the choice of primer pair, polymerase, PCR cycle and technical replication. However, few studies have assessed the accuracy and precision of different sequencing platforms. Here, we compared the performance of newly released DNBSEQ-G400 sequencer with that of the commonly used Illumina MiSeq platform by leveraging amplicon sequencing of a large number of soil samples. Significant sequencing bias among major fungal genera was found in parallel MiSeq runs, which can be easily neglected without the use of sequencing controls. We emphasize the importance of technical controls in large-scale sequencing efforts and provide DNBSEQ-G400 as an alternative with increased sequencing capacity and more stable reproducibility for amplicon sequencing.View Full Text

microbiology↗

bioRxiv2020

Decoding herbal materials of representative TCM preparations with the multi-barcoding approach

With the rapid development of high-throughput sequencing (HTS) technology, the techniques for the assessment of biological ingredients in Traditional Chinese Medicine (TCM) preparations have also advanced. By using HTS together with the multi-barcoding approach, all biological ingredients could be identified from TCM preparations in theory, as long as their DNA is present. The biological ingredients of a handful of classical TCM preparations were analyzed successfully based on this approach in previous studies. However, the universality, sensitivity and reliability of this approach used on TCM preparations remain unclear. Here, four representative TCM preparations, namely Bazhen Yimu Wan, Da Huoluo Wan, Niuhuang Jiangya Wan and You Gui Wan, were selected for concrete assessment of this approach. We have successfully detected from 77.8% to 100% prescribed herbal materials based on both ITS2 and trnL biomarkers. The results based on ITS2 have also shown a higher level of reliability than those of trnL at species level, and the integration of both biomarkers could provide higher sensitivity and reliability. In the omics big-data era, this study has undoubtedly made one step forward for the multi-barcoding approach for prescribed herbal materials analysis of TCM preparation, towards better digitization and modernization of drug quality control.

bioinformatics↗

bioRxiv2020

Fabrication and Modeling of Recessed Traces for Silicon-Based Neural Microelectrodes

Chronically-implanted neural microelectrodes are powerful tools for neuroscience research and emerging clinical applications, but their usefulness is limited by their tendency to fail after months in vivo. One failure mode is the degradation of insulation materials that protect the conductive traces from the saline environment. Studies have shown that material degradation is accelerated by mechanical stresses, which tend to concentrate on raised topographies such as conducting traces. Therefore, to avoid raised topographies, we developed a fabrication technique that recesses (buries) the traces in dry-etched, self-aligned trenches. The depth of the trenches and the thickness of the traces are matched so that overlying insulation materials are flat, which, according to finite-element modeling, reduces stress concentrations in the insulation material. Here, we provide details on process optimization, modeling of intrinsic stress, and characterization using SEM, focused ion-beam cross sections, profilometry, and electrochemical impedance testing. The technique requires no extra masks, is easy to integrate with existing processes, and produces flatness within about 10 nm.

bioengineering↗

bioRxiv2020

Intracellular Delivery of Nanoparticles via Microelectrophoresis Technique: Feasibility demonstration

Nanoparticles with desirable properties and functions have been actively developed for various bio-medical research, such as in vivo and in vitro sensors, imaging agents and delivery vehicles of therapeutics. However, an effective method to deliver nanoparticles into the intracellular environment is a major challenge and critical to many biological studies. Current techniques, such as intracellular uptake, electroporation and microinjection, each have their own set of benefits and associated limitations (e.g., aggregation and endosomal degradation of nanoparticles, high cell mortality and low throughput). Here, the well-established microelectrophoresis technique is applied for the first time to deliver nanoparticles into target cells, which overcomes some of these delivery difficulties. Semiconductive quantum dots, with average hydrodynamic diameter of 24.4 nm, have been successfully ejected via small electrical currents (-0.2 nA) through fine-tipped glass micropipettes as an example, into living human embryonic kidney cells (roughly 20 - 30m in length). As proposed by previous studies, micropipettes were fabricated to have an average tip inner diameter of 206 nm for ejection but less than 500 nm to minimize the cell membrane damage and cell distortion. In addition, delivered quantum dots were found to stay monodispersed within the cells for approximately one hour. We believe that microelectrophoresis technique may serve as a simple and general strategy for delivering a variety of nanoparticles intracellularly in various biological systems.

biochemistry↗

bioRxiv2020

Effects of emotion and semantic relatedness on recognition memory: Behavioral and electrophysiological evidence

Some aspects of our memory are enhanced by emotion, whereas other can be unaffected or even hindered. Previous studies report impaired associative memory of emotional content, an effect termed associative "emotional interference". The current study used EEG and an associative recognition paradigm to investigate the cognitive and neural mechanisms associated with this effect. In two experiments, participants studied negative and neutral stimulus-pairs that were either semantically related or unrelated. In Experiment 1 emotions were relevant to the encoding task (valence judgment) whereas in Experiment 2 emotions were irrelevant (familiarity judgment). In a subsequent associative recognition test, EEG was recorded while participants discriminated between intact, rearranged, and new pairs. An associative emotional interference effect was observed in both experiments, but was attenuated for semantically related pairs in Experiment 1, where valence was relevant to the task. Moreover, a modulation of an early associative memory ERP component (300-550 ms) occurred for negative pairs when valence was task-relevant (Experiment 1), but for semantically related pairs when valence was irrelevant (Experiment 2). A later ERP component (550-800 ms) showed a more general pattern, and was observed in all experimental conditions. These results suggest that both valence and semantic relations can act as an organizing principle that promotes associative binding. Their ability to contribute to successful retrieval depends on specific task demands.

neuroscience↗

bioRxiv2020

Intraspinal stimulation with silicon-based 3D microelectrode array for bladder voiding in cats before and after spinal cord injury

Bladder dysfunction is a significant and largely unaddressed problem for people living with spinal cord injury. Intermittent catheterization does not provide volitional control of micturition and has numerous side effects. Targeted electrical microstimulation of the spinal cord has been previously explored for restoring such volitional control in the animal model of experimental spinal cord injury. In this study, the development of the intraspinal microstimulation array technology was continued and evaluated in the feline animal model for its ability to provide more focused and reliable bladder control after a complete spinal cord transection. For the first time, the intraspinal multisite silicon array wad built using novel microfabrication processes to provide custom-designed tip geometry and 3D electrode distribution, better cost efficiency, reproducibility, scalability, and on-the-probe integration of active electronics. Long-term implantation was performed in 8 animals for a period up to 6 months, targeting the dorsal gray commissure area in the S1 sacral cord that is known to be involved in the coordination between the bladder detrusor and the external urethral sphincter. About one third of the electrode sites in the that area produced micturition-related responses. The effectiveness of stimulation increased starting from one month after spinal cord transection (as evaluated in one animal), likely due to supraspinal disinhibition of the spinal circuitry and/or hypertrophy and hyperexcitability of the spinal bladder afferents. Further studies are required to assess longer-term reliability of the developed intraspinal microstimulation array technology in preparation for eventual human translation.

bioengineering↗

bioRxiv2019

Over 50000 metagenomically assembled draft genomes for the human oral microbiome reveal new taxa

The oral cavity of each person is home for hundreds of bacterial species. While taxa for oral diseases have been well studied using culture-based as well as amplicon sequencing methods, metagenomic and genomic information remain scarce compared to the fecal microbiome. Here we provide metagenomic shotgun data for 3346 oral metagenomics samples, and together with 808 published samples, assemble 56,213 metagenome-assembled genomes (MAGs). 64% of the 3,589 species-level genome bins contained no publicly available genomes, others with only a handful. The resulting genome collection is representative of samples around the world and across physiological conditions, contained many genomes from Candidate phyla radiation (CPR) which lack monoculture, and enabled discovery of new taxa such as a family within the Acholeplasmataceae order. New biomarkers were identified for rheumatoid arthritis or colorectal cancer, which would be more convenient than fecal samples. The large number of metagenomic samples also allowed assembly of many strains from important oral taxa such as Porphyromonas and Neisseria. Predicted functions enrich in drug metabolism and small molecule synthesis. Thus, these data lay down a genomic framework for future inquiries of the human oral microbiome.

microbiology↗