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Zhou, X.

Publications and source records attributed to Zhou, X..

At least 631 records · Page 35Linked to original sources

Infection Groups Differential (IGD) Score Reveals Infection Ability Difference between SARS-CoV-2 and Other Coronaviruses

The Corona Virus Disease 2019 (COVID-19) pandemic that began in late December 2019 has resulted in millions of cases diagnosed worldwide. Reports have shown that SARS-CoV-2 shows extremely higher infection rates than other coronaviruses. This study conducted a phylogenetics analysis of 91 representative coronaviruses and found that the functional spike protein of SARS-CoV-2, which interacts with the human receptor ACE2, is actually not undergoing distinct selection pressure compared to other coronaviruses. Furthermore, we define a new measurement, infection group differential (IGD) score, in assessing the infection ability of two human coronavirus groups. There are nine extremely high IGD (ehIGD) sites in the receptor-binding domain (RBD) out of 40 high IGD (hIGD) sites that exhibit a unique infection-related pattern from the haplotype network and docking energy comparison. These 40 hIGD sites are basically conserved among the SARS-CoV-2, i.e. there are only two hIGD sites mutated in four out of 1,058 samples, defined as rare-mutation hIGD (rhIGD) sites. In conclusion, ehIGD and rhIGD sites might be of great significance to the development of vaccines.

bioinformatics↗

Structure of SARS-CoV-2 main protease in the apo state reveals the inactive conformation

Mpro is of considerable interest as a drug target in the treatment of COVID-19 since the proteolytic activity of this viral protease is essential for viral replication. Here we report the first insight of the structure Mpro for SARS-CoV-2 in the inactive conformation under conditions close to the physiological state (pH 7.5) to an overall resolution of 1.9 [A]. The comparisons of Mpro in different states reveal that substrate binding site and the active site are more flexible in the inactive conformation than that in the active conformations. Notably, compared with the active conformation of the apo state structure in pH7.6 of SARS, the SARS-CoV-2 apo state is in the inactive conformation under condition close to physiological state (pH7.5). Two water molecules are present in the oxyanion hole in our apo state structure, whereas in the ligand-bound structure, water molecular is absence in the same region. This structure provides novel and important insights that have broad implications for understanding the structural basis underlying enzyme activity, and can facilitate rational, structure-based, approaches for the design of specific SARS-CoV-2 ligands as new therapeutic agents.

biochemistry↗

Clinical and biomarker changes in sporadic Alzheimer's disease: Amyloid-β not useful marker for disease onset or progression

IMPORTANCEThe dynamic changes of biomarkers and clinical profiles in sporadic Alzheimers disease (SAD) are poorly understood. OBJECTIVETo evaluate the impact of amyloid-{beta} (A{beta}) biomarkers on SAD by measuring the dynamic changes in biomarkers and clinical profiles in the progression of SAD. DESIGN AND SETTINGThis retrospective and longitudinal study analyzed clinical and biomarker data from 665 participants (mean follow-up 4.90 {+/-} 2.83 years) from a subset of the AD Neuroimaging Initiative (ADNI) participants collected from August 2005 to December 2018. By aligning the timing of the changes in the various biomarkers with the stable normal cognition (CN) baseline and mild cognitive impairment (MCI) or AD onset timepoints, we combined data from the stable CN, CN conversion to MCI (CN2MCI), and MCI conversion to AD (MCI2AD) groups to identify the trajectories associated with the progression of AD. PARTICIPANTSThe participants were 294 CN, 69 CN2MCI, 300 MCI2AD, and 24 who converted from CN to MCI to AD (CN2MCI2AD) (of whom 22 were also included in the CN2MCI). EXPOSURESAmyloid-{beta} measured by florbetapir positron emission tomography (PET) or cerebrospinal fluid assay of amyloid-{beta} (CSF A{beta}42). MAIN OUTCOMES AND MEASURESThe measures included the 13-item cognitive subscale of the AD Assessment Scale (ADAS13, as a clinical measure), hippocampal volume, and the fluorodeoxyglucose (FDG) PET standardized uptake value ratio (SUVR). RESULTSThe CN, CN2MCI, and MCI2AD subgroups median (interquartile range [IQR]) annual changes in ADAS13 were (0.388 [-0.278, 0.818], 1.000 [0.239, 2.330], and 3.388 [1.750, 6.169]). The annual changes in hippocampal volume for each group were (-0.005 %ICV [-0.011, -0.001], -0.006 %ICV [-0.012, -0.002], and -0.014 %ICV [-0.021, -0.009]). The annual changes in FDG PET SUVR for each group were (-0.011 [-0.030, 0.010], -0.027 [-0.056, -0.012], and -0.039 [-0.063, 0.014]). Changes in the amyloid biomarkers were inconsistent with clinical profile changes. The annual changes in CSF A{beta}42 for each group were (-1.500 pg/ml [-6.000, 4.000], -2.200 [-5.667, 4.000], and -2.000 [-7.000, 2.650]) and in A{beta} PET SUVR for each group were (0.004 [-0.002, 0.012], 0.004 [-0.001,0.011], and 0.005 [-0.006, 0.014]). During the stable CN and CN2MCI stages, subjects with elevated and those with normal amyloid showed no significant differences (likelihood ratio test, p < .01) in clinical measures, hippocampal volume, or FDG. CONCLUSIONS AND RELEVANCEHippocampal volume and FDG associated with clinical profiles impairment in the SAD progression. A{beta} alone is not associated with clinical profiles, hippocampal volume, and FDG impairment in the preclinical stage of SAD. Key PointsQuestion: What is the role of amyloid-{beta} in dynamic changes in biomarkers and clinical profiles in the progression of sporadic Alzheimers disease? Findings: The changes of the hippocampal volume and FDG that were consistent with the changes of the clinical profiles showed a non-linear change in the initial stage and an accelerated non-linear change during MCI2AD, changes in amyloid biomarkers were inconsistent with the clinical profile. Cognitively normal people with elevated or normal amyloid showed no significant differences in clinical measures, hippocampal volume, or FDG. Meaning: Amyloid-{beta} alone may not be used as the central index for defining the preclinical stage of SAD.

neuroscience↗

Tumor neoantigen heterogeneity impacts bystander immune inhibition of pancreatic cancer growth

The threshold for immunogenic clonal fraction in a heterogeneous solid tumor required to induce effective bystander killing of non-immunogenic subclones is unknown. Pancreatic cancer poses crucial challenges for immune therapeutic interventions due to low mutational burden and consequent lack of neoantigens. Here, we designed a model to incorporate artificial neoantigens into genes of interest in cancer cells and to test the potential of said antigens to actuate bystander killing. By precisely controlling the abundance of a neoantigen in the tumor, we studied the impact of neoantigen frequency on immune response and immune escape. Our results showed that a single, strong, widely expressed neoantigen could lead to a robust antitumor response when at least 80% of cancer cells express the neoantigen. Further, immunological assays revealed induction of T-cell responses against a non-target self-antigen on KRAS oncoprotein, when we inoculated animals with a high frequency of tumor cells expressing a test neoantigen. Using nanoparticle-based gene therapy, we successfully altered the tumor microenvironment by perturbing interleukin-12 and interleukin-10 gene expression. The subsequent remodeling of the microenvironment reduced the threshold of neoantigen frequency at which bioluminescent signal intensity for tumor burden decreased 1.5-logfold, marking a robust tumor growth inhibition, from 83% to as low as 29%. Our results thus suggest that bystander killing is rather inefficient in immunologically cold tumors like pancreatic cancer and requires an extremely high abundance of neoantigens. However, the bystander killing mediated antitumor response can be rescued, when supported by adjuvant immune therapy.

cancer biology↗

Rapid adaptation of SARS-CoV-2 in BALB/c mice: Novel mouse model for vaccine efficacy

Coronavirus disease 2019 (COVID-19) threatens global public health and economy. In order to develop safe and effective vaccines, suitable animal models must be established. Here we report the rapid adaption of SARS-CoV-2 in BALB/c mice, based on which a convenient, economical and effective animal model was developed. Specifically, we found that mouse-adapted SARS-CoV-2 at passage 6 (MACSp6) efficiently infected both aged and young wild-type BALB/c mice, resulting in moderate pneumonia as well as inflammatory responses. The elevated infectivity of MACSp6 in mice could be attributed to the substitution of a key residue (N501Y) in the receptorbinding domain (RBD). Using this novel animal model, we further evaluated the in vivo protective efficacy of an RBD-based SARS-CoV-2 subunit vaccine, which elicited highly potent neutralizing antibodies and conferred full protection against SARS-CoV-2 MACSp6 challenge. This novel mouse model is convenient and effective in evaluating the in vivo protective efficacy of SARS-CoV-2 vaccine. SummaryThis study describes a unique mouse model for SARS-CoV-2 infection and confirms protective efficacy of a SARS-CoV-2 RBD subunit vaccine.

microbiology↗

Joint eQTL mapping and Inference of Gene Regulatory Network Improves Power of Detecting both cis- and trans-eQTLs

MotivationGenetic variations of expression quantitative trait loci (eQTLs) play a critical role in influencing complex traits and diseases development. Two main factors that affect the statistical power of detecting eQTLs are: 1) relatively small size of samples available, and 2) heavy burden of multiple testing due to a very large number of variants to be tested. The later issue is particularly severe when one tries to identify trans-eQTLs that are far away from the genes they influence. If one can exploit co-expressed genes jointly in eQTL-mapping, effective sample size can be increased. Furthermore, using the structure of the gene regulatory network (GRN) may help to identify trans-eQTLs without increasing multiple testing burden. ResultsIn this paper, we employ the structure equation model (SEM) to model both GRN and effect of eQTLs on gene expression, and then develop a novel algorithm, named sparse SEM, for eQTL mapping (SSEMQ) to conduct joint eQTL mapping and GRN inference. The SEM can exploit co-expressed genes jointly in eQTL mapping and also use GRN to determine trans-eQTLs. Computer simulations demonstrate that our SSEMQ significantly outperforms eight existing eQTL mapping methods. SSEMQ is further employed to analyze a real dataset of human breast tissues, yielding a number of cis- and trans-eQTLs. AvailabilityR package ssemQr is available on https://github.com/Ivis4ml/ssemQr.git.

bioinformatics↗

Stearoyl-CoA desaturase mediated monounsaturated fatty acid availability supports humoral immunity

ABSTRACTImmune cells can metabolize glucose, amino acids, and fatty acids (FAs) to generate energy. The role of different FA species, and their impacts on humoral immunity remains poorly understood. Here we report that proliferating B cells require monounsaturated FAs (MUFA) to maintain mitochondrial metabolism and mTOR activity, and to prevent excessive autophagy and endoplasmic reticulum (ER) stress. Furthermore, B cell extrinsic Stearoyl-CoA desaturase (SCD) activity generates MUFA to support early B cell development and germinal center (GC) formation in vivo during immunization and influenza infection. Thus, SCD-mediated MUFA production is critical for humoral immunity.Competing Interest StatementThe authors have declared no competing interest.View Full Text

immunology↗

Cells recognize osmotic stress through liquid-liquid phase separation lubricated with poly(ADP-ribose)

Cells are under threat of osmotic perturbation; and cell volume maintenance is critical in cerebral edema, inflammation and aging, in which prominent changes in intracellular or extracellular osmolality emerge. After osmotic stress-enforced cell swelling or shrinkage, the cells regulate intracellular osmolality to recover their volume. However, the mechanisms recognizing osmotic stress remain obscured. We previously clarified that apoptosis signal-regulating kinase 3 (ASK3) bidirectionally responds to osmotic stress and regulates cell volume recovery. Here, we report that macromolecular crowding induces liquid-demixing condensates of ASK3 under hyperosmotic stress, which transduce osmosensing signal into ASK3 inactivation. A genome-wide small interfering RNA (siRNA) screen identified an ASK3 inactivation regulator, nicotinamide phosphoribosyltransferase (NAMPT), related to poly(ADP-ribose) signaling. Furthermore, we clarify that poly(ADP-ribose) keeps ASK3 condensates in the liquid phase and enables ASK3 to become inactivated under hyperosmotic stress. Our findings demonstrate that cells rationally incorporate physicochemical phase separation into their osmosensing systems.

cell biology↗

Functional Interrogation of HOXA9 Regulome in MLLr Leukemia via Reporter-based CRISPR/Cas9 screen

Aberrant HOXA9 expression is a hallmark of most aggressive acute leukemias, including human acute myeloid leukemia (AML) and subtypes of acute lymphoblastic leukemia (ALL). HOXA9 overexpression not only predicts poor diagnosis and outcome but also plays a critical role in leukemia transformation and maintenance. However, our current understanding of HOXA9 regulation in leukemia is limited, hindering development of therapeutic strategies to treat HOXA9-driven leukemia. To mitigate these challenges, we generated the first HOXA9-mCherry knock-in reporter in an MLL-rearranged (MLLr) B-ALL cell line to dissect HOXA9 regulation. By utilizing the reporter and CRISPR/Cas9 mediated screens, we identified transcription factors controlling HOXA9 expression, including a novel regulator, USF2 and its homolog USF1. USF1/USF2 depletion significantly down-regulated HOXA9 expression and impaired MLLr leukemia cell proliferation. Ectopic expression of HOXA9-MEIS1 fusion protein rescued the impaired leukemia cell proliferation upon USF2 loss. Cut&Run analysis revealed the direct occupancy of USF2 onto HOXA9 promoter in MLLr leukemia cells. Collectively, the HOXA9 reporter facilitated the functional interrogation of the HOXA9 regulome and has advanced our understanding of the molecular regulation network in HOXA9-driven leukemia.

cancer biology↗

An aptamer-based magnetic flow cytometer using matched filtering

Facing unprecedented population-ageing, the management of noncommunicable diseases (NCDs) urgently needs a point-of-care (PoC) testing infrastructure. Magnetic flow cytometers are one such solution for rapid cancer cellular detection in a PoC setting. In this work, we report a giant magnetoresistive spin-valve (GMR SV) biosensor array with a multi-stripe sensor geometry and matched filtering to improve detection accuracy without compromising throughput. The carefully designed sensor geometry generates a characteristic signature when cells labeled with magnetic nanoparticles (MNPs) pass by thus enabling multi-parametric measurement like optical flow cytometers (FCMs). Enumeration and multi-parametric information were successfully measured across two decades of throughput. 10-{micro}m polymer microspheres were used as a biomimetic model where MNPs and MNP-decorated polymer conjugates were flown over the GMR SV sensor array and detected with a signal-to-noise ratio (SNR) as low as 2.5 dB due to the processing gain afforded by the matched filtering. The performance was compared against optical observation, exhibiting a 92% detection efficiency. The system achieved a 95% counting accuracy for biomimetic models and 98% for aptamer-based pancreatic cancer cell detection. This system demonstrates the ability to perform reliable PoC diagnostics towards the benefit for NCD control plans.

bioengineering↗

Demystifying "drop-outs" in single cell UMI data

Analysis of scRNA-seq data has been challenging particularly because of excessive zeros observed in UMI counts. Prevalent opinions are that many of the detected zeros are "drop-outs" that occur during experiments and that those zeros should be accounted for through procedures such as normalization, variance stabilization, and imputation. Here, we extensively analyze publicly available UMI datasets and challenge the existing scRNA-seq workflows. Our results strongly suggest that resolving cell-type heterogeneity should be the foremost step of the scRNA-seq analysis pipeline because once cell-type heterogeneity is resolved, "drop-outs" disappear. Additionally, we show that the simplest parametric count model, Poisson, is sufficient to fully leverage the biological information contained in the UMI data, thus offering a more optimistic view of the data analysis. However, if the cell-type heterogeneity is not appropriately taken into account, pre-processing such as normalization or imputation becomes inappropriate and can introduce unwanted noise. Inspired by these analyses, we propose a zero inflation test that can select gene features contributing to cell-type heterogeneity. We integrate feature selection and clustering into iterative pre-processing in our novel, efficient, and straightforward framework for UMI analysis, HIPPO (Heterogeneity Inspired Pre-Processing tOol). HIPPO leads to downstream analysis with much better interpretability than alternatives in our comparative studies.

genomics↗

Orthogonal genome-wide screenings in bat cells identify MTHFD1 as a target of broad antiviral therapy

Bats are responsible for the zoonotic transmission of several major viral diseases including the 2003 SARS outbreak and the ongoing COVID-19 pandemic. While bat genomic sequencing studies have revealed characteristic adaptations of the innate immune system, functional genomic studies are urgently needed to provide a foundation for the molecular dissection of the tolerance of viral infections in bats. Here we report the establishment and screening of genome-wide RNAi library and CRISPR library for the model megabat, Pteropus Alecto. We used the complementary RNAi and CRISPR libraries to interrogate Pteropus Alecto cells for infection with two different viruses, mumps virus and Influenza A virus, respectively. Screening results converged on the endocytosis pathway and the protein secretory pathway as required for both viral infections. Additionally, we revealed a general dependence of the C-1-tetrahydrofolate synthase gene, MTHFD1, for viral replication in bat cells as well as in human cells. MTHFD1 inhibitor carolacton potently blocked replication of several RNA viruses including SARS-CoV-2. Our studies provide a resource for systematic inquiry into the genetic underpinnings of bat biology and a potential target for developing broad spectrum antiviral therapy.

microbiology↗

Assessing the statistical reporting quality in high-impact factor urology journals

BackgroundsObservational studies plays an important role in urology studies, But few studies have paid attention to the statistical reporting quality of observational studies. The purpose of this study was to investigate the frequency and evaluate the reporting quality of statistical methods of the published observational studies in urology. MethodsThe five urology journals were selected according to the 5-year impact factor. A systematic literature search was performed in PubMed for relevant articles. The quality of statistical reporting was assessed according to assessment criteria. ResultsA total of 193 articles were included in this study. The mean statistical reporting score of included articles was 0.42 (SD=0.15), accounting for 42% of total score. The items that must be reported with a reporting rate more than 50% were: alpha level (n=122, 65.2%), confidence intervals (n=134, 69.4%), name of statistical package (n=158, 84.5%) and exact P-values (n=161, 86.1%). The items with a reporting rate less than 50% were: outliers (n=2, 1.0%) and sample size (n=13, 6.7%). For multivariable regression models (liner, logistic and Cox), variables coding (n=27, 40.7%), validation analysis of assumptions (n=58, 40.3%), interaction test (n=43, 30.0%), collinearity diagnostics (n=5, 3.5%) and goodness of fit test (n=6, 5.9%) were reported. Number of authors more than 7(OR=2.06, 95%CI=1.04-4.08) and participation of statistician or epidemiologist (OR=1.73, 95%CI=1.18-3.39) were associated with the superior reporting quality. ConclusionThe statistical reporting quality of published observational studies in 5 high-impact factor urological journals was alarming. We encourage researchers to collaborate with statistician or epidemiologist. The authors, reviewers and editors should increase their knowledge of statistical methods, especially new and complex methods.

systems biology↗

Accurate Diagnosis of Colorectal Cancer Based on Histopathology Images Using Artificial Intelligence

BackgroundAccurate and robust pathological image analysis for colorectal cancer (CRC) diagnosis is time-consuming and knowledge-intensive, but is essential for CRC patients treatment. The current heavy workload of pathologists in clinics/hospitals may easily lead to unconscious misdiagnosis of CRC based on their daily image analyses. MethodsBased on a state-of-the-art transfer-learned deep convolutional neural network in artificial intelligence (AI), we proposed a novel patch aggregation strategy for clinic CRC prediction/diagnosis using weakly labeled pathological whole slide image (WSI) patches. This approach was trained and validated using an unprecedented and enormously large number of 170,099 patches, >14,680 WSIs, from >9,631 subjects that covered diverse and representative clinical cases from multi-independent-sources across China, U.S., and Germany. ResultsOur innovative AI tool was consistently nearly perfectly agreed with (average Kappa-statistic 0.896) and even often better than most of the experienced expert pathologists when tested in diagnosing CRC WSIs from multi-centers. The average area under the receiver operating characteristics curve (AUC) of AI was greater than that of the pathologists (0.981 vs 0.970) and achieved the best performance among the application of other AI methods to CRC diagnosis. Our AI-generated heatmap highlights the image regions of cancer tissue/cells. ConclusionsThis first-ever generalizable AI system can handle large amounts of WSIs consistently and robustly without potential bias due to fatigue commonly experienced by clinical pathologists. Hence, it will drastically alleviate the heavy clinical burden of daily pathology diagnosis, and improve the treatment for CRC patients. This tool is generalizable to other cancer diagnosis based on image recognition.

pathology↗

Oxytocin differentially modulates amygdala responses during top-down and bottom-up aversive anticipation

The ability to successfully regulate negative emotions such as fear and anxiety is vital for mental health. The neuropeptide oxytocin (OXT) acts as important modulator of emotion regulation, as reflected by reduced amygdala responses but increased amygdala-prefrontal cortex (PFC) functional connectivity in response to threatening stimuli. The present randomized, between-subject, placebo (PLC)-controlled pharmacological study combined intranasal administration of OXT with functional MRI during an explicit (cognitive) emotion regulation (i.e. distancing reappraisal) paradigm in 65 healthy male participants to investigate the modulatory effects of OXT on both bottom-up and top-down emotion regulation. OXT attenuated the activation in posterior insular cortex and amygdala during anticipation of top-down regulation of predictable threat stimuli in participants with high trait anxiety, providing evidence to support the anxiolytic action of OXT. In contrast, OXT enhanced amygdala activity during bottom-up anticipation of an unpredictable threat stimulus in participants with low trait anxiety. OXT may thus facilitate top-down goal-directed attention by attenuating amygdala activity in high anxiety individuals, while promote bottom-up attention/vigilance to unexpected threat by enhancing anticipatory amygdala activity in low anxiety individuals. The opposite effects of OXT on anticipatory amygdala activation in high versus low anxiety individuals may suggest a baseline anxiety level dependent mechanism via which OXT promotes optimal levels of amygdala activation during the anticipation of an imminent threat. OXT may thus have the potential to promote an adaptive balance between bottom-up and top-down attention systems depending on individual levels of pre-treatment trait anxiety levels.

neuroscience↗

Bbs5 functions as the docking compartment of Bbsome binding to Klc3 regulated by Bbs5-Ser246 PKC-phosphorylation during mouse spermatogenesis

A mitochondrial and a fibrous sheath form the midpiece of the mammalian sperm flagellum encircling most of the axoneme. It has been documented that Kinesin light chain 3 (KLC3) was involved although the formation procedure remains unclear. Yeast-two-hybrid dataset showed an interaction between Klc3 and Bardet-Biedl Syndrome 5 (BBS5) Protein, another molecular associated with cilia and flagella forming. In this study, we presumed that the most conserved IFT complex BBsome was involved in spermatogenesis via the interaction of one of its subunits, Bbs5 with Klc3. Firstly, the interaction between Klc3 and Bbs5 was confirmed with Co-IP. Secondly, we identified PKC phosphorylation sites in vitro by LC-MS/MS, Ser19 and Ser246 of Bbs5, examined the phosphorylation status of Bbs5 Ser19 and Ser246 in mouse testis. Co-IP was performed to find which PKC isoforms phosphorylate Bbs5. In addition, we tried to discuss the roles of Ser19 and Ser246 of Bbs5 in the Klc3-bbs5 interaction and in mouse spermatogenesis based on our early findings.

cell biology↗

Chromosome-Scale Genome Assembly Provides Insights into Speciation of Allotetraploid and Massive Biomass Accumulation of Elephant Grass (Pennisetum purpureum Schum.)

Elephant grass (Pennisetum purpureum Schum., AABB, 2n=4x=28), which is characterized as robust growth and high biomass, and widely distributed in tropical and subtropical areas globally, is an important forage, biofuels and industrial plant. We sequenced its allopolyploid genome and assembled 2.07 Gb (96.88%) into A and B sub-genomes of 14 chromosomes with scaffold N50 of 8.47 Mb. A total of 38,453 and 36,981 genes were annotated in A and B sub-genomes, respectively. A phylogenetic analysis with species in Pennisetum identified that the speciation of the allotetraploid occurred approximately 15 MYA after the divergence between S.italica and P. glaucum. Double whole-genome duplication (WGD) and polyploidization events resulted in large scale gene expansion, especially in the key steps of growth and biomass accumulation. Integrated transcriptome profiling revealed the functional differentiation between sub-genomes; A sub-genome contributed more to plant growth, development and photosynthesis whereas B sub-genome primarily offered functions of effective transportation and resistance to stimulation. The results uncovered enhanced cellulose and lignin biosynthesis pathways with 645 and 666 genes expanded in A and B sub-genomes, respectively. Our findings provided deep insights into the speciation and genetic basis of fast growth and high biomass accumulation in the species. The genetic, genomic, and transcriptomic resources generated in this study will pave the way for further domestication and selection of these economical species and making them more adaptive to industrial utilization.

genomics↗

A quantitative framework reveals the ecological drivers of grassland soil microbial community assembly in response to warming

Unraveling the drivers controlling community assembly is a central issue in ecology. Selection, dispersal, diversification and drift are conceptually accepted as major community assembly processes. Defining their relative importance in governing biodiversity is compellingly needed, but very challenging. Here, we present a novel framework to quantitatively infer community assembly mechanisms by phylogenetic bin-based null model analysis (iCAMP). Our results with simulated microbial communities showed that iCAMP had high accuracy (0.93 - 0.99), precision (0.80 - 0.94), sensitivity (0.82 - 0.94), and specificity (0.95 - 0.98), which were 10-160% higher than those from the entire community-based approach. Applying it to grassland microbial communities in response to experimental warming, our analysis showed that homogeneous selection (38%) and "drift" (59%) played dominant roles in controlling grassland soil microbial community assembly. Interestingly, warming enhanced homogeneous selection, but decreased "drift" over time. Warming-enhanced selection was primarily imposed on Bacillales in Firmicutes, which were strengthened by increased drought and reduced plant productivity. This general framework should also be useful for plant and animal ecology.

ecology↗