Biology subjects

Meng, X.

Publications and source records attributed to Meng, X..

At least 109 records · Page 6Linked to original sources

bioRxiv2022

Integrate multiscale module kernel for disease-gene discovery in biological networks

Biomedical data mining plays a crucial role in studying diseases, with disease-gene identification being one of the most prominent areas of research in this field. Many biomolecule networks are known to have multi-scale module structures, which may be helpful for studying complex diseases, but the mining and utilization of multi-scale module structure is an open issue. Therefore, we present a kind of novel hybrid network-based method (HyMSMK) for disease-gene identification through incorporating multi-scale module kernel in biomolecule networks. We first apply exponential sampling to construct multi-scale module profile containing local to global structural information, where modules at different scales are extracted from comprehensive interactome by multi-scale modularity optimization. Then, the multi-scale module profile is preprocessed by the relative information content, and is used to generate multi-scale module kernel, which is further preprocessed by kernel sparsification. We design multiple schemes for incorporating multi-scale module kernel to discover potential disease-related genes. We investigate the performance of these schemes by experimental evaluations, show the positive effect of kernel sparsification on reducing the requirement for space and time, and confirm the superior performance of our method compared to other state-of-art network-based baselines. The study demonstrates the utility of multi-scale module kernel in discovering disease genes, which could provide insights for the research of relevant issues.

bioinformatics↗

bioRxiv2022

Strain dropouts reveal interactions that govern the metabolic output of the gut microbiome

The gut microbiome is complex, raising questions about the role of individual strains in the community. Here, we address this question by focusing on a functional unit within the community, the metabolic niche that controls bile acid 7-dehydroxylation. By constructing variants of a complex defined community in which we drop out strains that occupy this niche, we explore how interactions within and between niches shape community-level metabolism. Omitting both members of the niche, Clostridium scindens (Cs) and Clostridium hylemonae (Ch), eliminates secondary bile acid production and reshapes the community in a highly specific manner: eight strains go up or down in relative abundance by >100-fold, while the remaining strains are largely unaffected. In single-strain dropout communities (i.e., a strain swap within the niche), Cs and Ch reach the same relative abundance and dehydroxylate bile acids to a similar extent. However, the effect on strains in other niches differs markedly: Clostridium sporogenes increases >1000-fold in the {Delta}Cs but not {Delta}Ch dropout, reshaping the pool of microbiome-derived phenylalanine metabolites. Thus, strains that are functionally redundant within a niche can have widely varying impacts outside the niche, and a strain swap can ripple through the community in an unpredictable manner, resulting in a large impact on an unrelated community-level phenotype. Mice colonized by the {Delta}Cs{Delta}Ch community show decreased liver steatosis relative to those colonized by the {Delta}Ch community, demonstrating that a single strain from the microbiome can have a substantive impact on host physiology. Our work opens the door to the mechanistic studies of the role of an individual strain on community ecology and host physiology.

microbiology↗

bioRxiv2022

Multi-ancestry GWAS of major depression aids locus discovery, fine-mapping, gene prioritisation, and causal inference

Most genome-wide association studies (GWAS) of major depression (MD) have been conducted in samples of European ancestry. Here we report a multi-ancestry GWAS of MD, adding data from 21 studies with 88,316 MD cases and 902,757 controls to previously reported data from individuals of European ancestry. This includes samples of African (36% of effective sample size), East Asian (26%) and South Asian (6%) ancestry and Hispanic/Latinx participants (32%). The multi-ancestry GWAS identified 190 significantly associated loci, 53 of them novel. For previously reported loci from GWAS in European ancestry the power-adjusted transferability ratio was 0.6 in the Hispanic/Latinx group and 0.3 in each of the other groups. Fine-mapping benefited from additional sample diversity: the number of credible sets with [≤]5 variants increased from 3 to 12. A transcriptome-wide association study identified 354 significantly associated genes, 205 of them novel. Mendelian Randomisation showed a bidirectional relationship with BMI exclusively in samples of European ancestry. This first multi-ancestry GWAS of MD demonstrates the importance of large diverse samples for the identification of target genes and putative mechanisms.

genetics↗

bioRxiv2022

Oscillatory mechanisms of intrinsic brain networks

Neuroimaging studies of hemodynamic fluctuations have shown specific network-based organization of the brain at rest, yet the neurophysiological underpinning of these networks in human brain remain unclear. Here, we recorded resting-state activities of neuronal populations in the key regions of default mode network (DMN, posterior cingulate cortex and medial prefrontal cortex), frontoparietal network (FPN, dorsolateral prefrontal cortex and inferior parietal lobule), and salience network (SN, anterior insula and dorsal anterior cingulate cortex) from 42 human participants using intracranial electroencephalogram (iEEG). We observed stronger within-network connectivity of the DMN, FPN and SN in broadband iEEG power, stronger phase synchronization within the DMN across theta and alpha bands, and weaker phase synchronization within the FPN in delta, theta and alpha band. We also found positive power correlations in high frequency band (70-170Hz) and negative power correlations in alpha and beta band for FPN-DMN and FPN-SN. Robust negative correlations in DMN-SN were found in alpha, beta and gamma band. These findings provide intracranial electrophysiological evidence in support of the network model for intrinsic organization of human brain and shed light on the way how the brain networks communicate at rest.

neuroscience↗

bioRxiv2022

TPH2 knockout male rats are aggressive, show less anxiety, and exhibit an altered oxytocin system

The central serotoninergic system is critical for stress responsivity and social behavior, and its dysregulations has been centrally implicated in virtually all neuropsychiatric disorders. Genetic serotonin depletion animal models could provide a tool to elucidate the causes and mechanisms of diseases and to develop new treatment approaches. Previously mice lacking tryptophan hydroxylase 2 (Tph2) have been developed, showing altered behaviors and neurotransmission. However, the effect of congenital serotonin deficiency on emotional and social behavior in rats is still largely unknown, as are the underlying mechanisms. In this study, we used Tph2 knockout (Tph2-/-) male rat model to study how the lack of serotonin in the rat brain affects anxiety-like and social behaviors. Since oxytocin is centrally implicated in these behaviors, we furthermore explored whether effects of Tph2 knockout on behavior would relate to changes in the oxytocin system. We show that Tph2-/- rats display reduced anxiety-like behavior and a high level of aggression in social interactions. In addition, oxytocin receptor expression was increased in the infralimbic and prelimbic cortex, paraventricular nucleus, dorsal raphe nucleus and some subregions of hippocampus, which was paralleled by increased levels of oxytocin in the medial frontal cortex, paraventricular nucleus, but not the dorsal raphe nucleus, central amygdala and hippocampus. In conclusion, our study demonstrated reduced anxiety but exaggerated aggression in Tph2-/- male rats and reveals for the first time a potential involvement of altered oxytocin system function. SIGNIFICANCE STATEMENTWe explored the changes in behavior and oxytocin system functioning in the tryptophan hydroxylase 2 (Tph2) knockout rat model, lacking serotonin in the brain. This rat model contributes to our understanding of the role of serotonin in psychiatric transdiagnostic features and underlying mechanisms. We found that Tph2 knockout male rats are aggressive, less anxious, and exhibit an altered oxytocin system. The observed changes in oxytocin signaling may lead to a new target for the treatment of diseases caused by genetic serotonin deficiency.

neuroscience↗

bioRxiv2022

A transcriptional complex of FtMYB102 and FtbHLH4 coordinately regulates the accumulation of rutin in Fagopyrum tataricum

Tartary buckwheat is rich in flavonoids, which not only play an important role in plant-environment interaction, but are also beneficial to human health. Rutin is a therapeutic flavonol which is massively accumulated in Tartary buckwheat. It has been demonstrated that transcription factors control rutin biosynthesis. However, the transcriptional regulatory network of rutin is not fully clear. In this study, through transcriptome and target metabolomics, we validated the role of FtMYB102 and FtbHLH4 TFs at the different developmental stages of Tartary buckwheat. The elevated accumulation of rutin in the sprout appears to be closely associated with the expression of FtMYB102 and FtHLH4. Yeast two-hybrid, transient luciferase activity and co-immunoprecipitation demonstrated that FtMYB102 and FtbHLH4 can interact and form a transcriptional complex. Moreover, yeast one-hybrid showed that both FtMYB102 and FtbHLH4 directly bind to the promoter of chalcone isomerase (CHI), and they can coordinately induce CHI expression as shown by transient luciferase activity assay. Finally, we transferred the FtMYB102 and FtbHLH4 into the hairy roots of Tartary buckwheat and found that they both can promote the accumulation of rutin. Our results indicate that FtMYB102 and FtbHLH4 can form a transcriptional complex by inducing CHI expression to coordinately promote the accumulation of rutin.

plant biology↗

bioRxiv2022

Mapping the T cell repertoire to a complex gut bacterial community

Certain bacterial strains from the microbiome induce a potent, antigen-specific T cell response1-5. However, the specificity of microbiome-induced T cells has not been explored at the strain level across the gut community. Here, we colonize germ-free mice with a complex defined community (97 or 112 bacterial strains) and profile T cell responses to each strain individually. Unexpectedly, the pattern of T cell responses suggests that many T cells in the gut repertoire recognize multiple bacterial strains from the community. We constructed T cell hybridomas from 92 T cell receptor (TCR) clonotypes; by screening every strain in the community against each hybridoma, we find that nearly all of the bacteria-specific TCRs exhibit a one-to-many TCR-to-strain relationship, including 13 abundant TCR clonotypes that are polyspecific for 18 Firmicutes in the community. By screening three pooled bacterial genomic libraries against 13 pooled hybridomas, we discover that they share a single target: a conserved substrate-binding protein (SBP) from an ABC transport system. Treg and Th17 cells specific for an epitope from this protein are abundant in community-colonized and specific-pathogen-free mice. Our work reveals that T cell recognition of Firmicutes is focused on a widely conserved cell-surface antigen, opening the door to new therapeutic strategies in which colonist-specific immune responses are rationally altered or redirected.

immunology↗

bioRxiv2022

Integrated molecular and pharmacological characterization of patient-derived xenografts from bladder and ureteral cancers identifies new potential therapies.

BackgroundMuscle-invasive bladder cancer (MIBC) and upper urinary tract urothelial carcinoma (UTUC) are molecularly heterogeneous. Despite chemotherapies, immunotherapies or anti-FGFR treatments, these tumors are still of poor outcome. Our objective was to develop a bank of patient-derived xenografts (PDXs) recapitulating molecular heterogeneity of MIBC and UTUC, to facilitate preclinical identification of therapies. MethodsFresh tumors were obtained from patients and subcutaneously engrafted into immune-compromised mice. Patient tumors and matched PDXs were compared regarding histopathology, transcriptomic (microarrays) and genomic profiles (targeted-NGS). Several PDXs were treated with chemotherapy (cisplatin/gemcitabine) or targeted therapies (FGFR and EGFR inhibitors). Results31 PDXs were established from 1 non-MIBC, 25 MIBC, 5 upper urinary tract tumors, including 28 urothelial (UCC) and 3 squamous-cell carcinomas (SCC). Integrated genomic and transcriptomic profiling identified PDXs of 3 different consensus molecular subtypes (Basal/Squamous, Luminal papillary and Luminal unstable), and included FGFR3-mutated PDXs. High histological and genomic concordance was found between matched patient tumor/PDX. Discordance in molecular subtypes, such as a basal/squamous patient tumor giving rise to a luminal papillary PDX, was observed (n=5) at molecular and histological levels. Ten models were treated with cisplatin-based chemotherapy and we did not observe association between subtypes and response. Of the 3 basal/squamous models treated with anti-EGFR therapy, two models were sensitive and one model, of sarcomatoid variant, was resistant. Treatment of 3 FGFR3-mutant PDXs with combined FGFR/EGFR inhibitors was more efficient than anti-FGFR3 treatment alone. ConclusionsWe developed preclinical PDX models that recapitulate the molecular heterogeneity of MIBCs and UTUC, including actionable mutations, which will represent an essential tool in therapy development. Pharmacological characterization of the PDXs suggested that upper urinary tract and MIBCs, UCC but also SCC, with similar molecular characteristics could benefit from the same treatments including anti-FGFR for FGFR3-mutated tumors and anti-EGFR for basal ones and showed a benefit for combined FGFR/EGFR inhibition in FGFR3-mutant PDXs, compared to FGFR inhibition alone.

cancer biology↗

bioRxiv2022

Fertilizer reduction with bio-organic fertilizer to regulate the root soil microbial community structure to improve Baby Chinese cabbage yield

Using high-throughput sequencing, this study aimed to explore the response of soil microbial community and Baby Chinese cabbage yield to the reduction of chemical fertilizers combined with bio-organic fertilizer in the Gansu plateau, China. Our experiments consisted of conventional fertilizer (CK), 30% chemical fertilizer reduction + 6,000 kg bio-organic fertilizer (T1), 30% chemical fertilizer reduction + 9,000 kg bio-organic fertilizer (T2), 40% chemical fertilizer reduction + 6,000 kg bio-organic fertilizer (T3), and 40% chemical fertilizer reduction + 9,000 kg bio-organic fertilizer (T4). Compared with CK, soil microbial diversity and richness were higher for all treatments with added bio-organic fertilizer. PCoA showed that the bacterial and fungal communities in T2 and T4 were similar to each other. Redundancy and Spearmans correlation analyses of microbial communities and soil physicochemical properties revealed that reductions in chemical fertilizer rate combined with bio-organic fertilizer had a stronger impact on the fungal than the bacterial community. They also increased the relative abundance of the dominant bacterial and fungal phyla. Baby Chinese cabbage yield was relatively higher under the combined bio-organic fertilizer plus reduced chemical fertilizer rate with T2 showing the highest yield. Therefore, this approach is feasible for sustainable agricultural, cost-effective and profitable crop production. ImportanceO_LIBio-organic + moderately reduced chemical fertilizer raised Chinese cabbage yield C_LIO_LIBio-organic + chemical fertilizer was more efficacious than either one alone C_LIO_LIPresence of bio-organic fertilizer enhanced overall rhizosphere physicochemistry C_LIO_LIBio-organic fertilizer improved beneficial bacterial & fungal abundance & diversity C_LIO_LIFertilizer combination sustainably & cost-effectively improves crop & soil quality C_LI

microbiology↗

bioRxiv2022

Balancing activation and costimulation of CAR tunes signaling dynamics and enhances therapeutic potency

BackgroundPrimary human T cells engineered with chimeric antigen receptors (CARs) ex vivo can be adoptively transferred to treat cancer. CD19-targeting CAR with CD28 costimulatory domain and CD3{zeta} activation domain have been approved by the US FDA for treating B cell malignancies. MethodsHere we generated mutation of immunorecpetor tyrosine-based activation motifs (ITAMs) in CD3{zeta}, namely 1XX CAR, which altered the balance of activation and costimulation. Next we investigated whether 1XX design could enhance therapeutic potency against solid tumors. We constructed both CD19- and AXL-specific 1XX CARs and compared their in vitro and in vivo functions with their WT counterparts. ResultsEven though 1XX CARs decreased cytotoxicity against tumor cells in vitro, they showed better anti-tumor efficacy in both pancreatic and melanoma mouse models. Detailed analysis revealed that 1XX CAR-T cells proliferated more in response to antigen stimulation in vitro, persisted longer in vivo and had higher percentage of central memory cells. As 1XX modification directly calibrates CAR activation potential, we utilized fluorescence resonance energy transfer (FRET)-based biosensor to monitor signaling dynamics downstream of CARs. Decreased ITAM numbers in 1XX resulted in similar ZAP70 activation, while 1XX induced higher Ca2+ elevation and faster Erk activation than WT CAR, which may contribute to the better therapeutic potency of 1XX. ConclusionsOur results established the surpiosity of 1XX against two targets in different solid tumor models and shed light on the underlying molecular mechanism of CAR signaling, paving the way for the clinical application of 1XX CARs against solid tumors.

immunology↗

bioRxiv2022

Profiling of the human intestinal microbiome and bile acids under physiologic conditions using an ingestible sampling device

The spatiotemporal structure of the human microbiome and metabolome reflects and determines regional intestinal physiology and may have implications for disease. Yet, we know little about the distribution of microbes and their products in the gut because of reliance on stool samples and limited access only to some regions of the gut using endoscopy in fasting or sedated individuals. To address these deficiencies, we developed and evaluated a safe, ingestible device that collects samples from multiple regions of the human intestinal tract during normal digestion. The collection of 240 intestinal samples from 15 healthy individuals using the device revealed significant differences between microbes and metabolites present in the intestines versus stool. Certain microbial taxa were differentially enriched, and bile acid profiles varied along the intestines and were highly distinct from those of stool. Correlations between gradients in bile acid concentrations and microbial abundance predicted species that altered the bile acid pool through deconjugation. Overall, we identified heterogeneous intestinal profiles of bacterial taxa and metabolites indicating that non-invasive multi-regional sampling of the intestinal tract under physiological conditions can help elucidate the roles of the gut microbiome and metabolome in human physiology and disease.

microbiology↗

bioRxiv2021

Boron Supply Restores Aluminum-Blocked Auxin Transport by Modulation PIN2 Trafficking in the Arabidopsis Roots

This study tested a hypothesis that boron (B) supply alleviates aluminum (Al) toxicity by modifying auxin distribution in functionally different root zones. Auxin distribution and transport at various Al and B ratios were analyzed using the range of molecular and imaging techniques. Al stress resulted in increased auxin accumulation in root apical meristem (MZ) and transition zones (TZ) while reducing its content in elongation zone (EZ). This phenomenon was explained by reduction in basipetal auxin transport caused by Al blockage of PIN2 endocytosis, regulated at posttranscriptional level. This inhibition of PIN2 endocytosis was dependent on actin filaments and microtubules. B supply facilitated the endocytosis and exocytosis of PIN2 carriers via recycling endosomes conjugated with IAA to modify Al-induced auxin depletion in the EZ. However, disruption of auxin signaling with auxinole did not alleviate Al-induced inhibition of root growth. B supply alleviates Al-induced inhibition of root growth via restoring the endocytic recycling of PIN2 proteins involved in the basipetal (shootward) auxin transport, restoring Al-induced auxin depletion in the elongation zone. Short summaryAluminum-intensified PIN2 abundance, nontranscriptional, via repressing PIN2 endocytosis to block polar auxin transport, and this adverse effect could be alleviated by boron supply.

physiology↗

bioRxiv2021

Vertical transmission of tissue microbiota in Caenorhabditis elegans

The past forty-five years has witnessed Caenorhabditis elegans as the most significant model animal in life science since its discovery seventy years ago1,2, as it introduced principles of gene regulated organ development, and RNA interference into biology3-5. Meanwhile, it has become one of the lab animals in gut microbiota studies as these symbionts contribute significantly to many aspects in host biology6,7. Meanwhile, the origin of gut microbiota remains debatable in human8- 11, and has not been investigated in other model animals. Here we show that the symbiont bacteria in C. elegans not only vertically transmit from the parent generation to the next, but also distributes in the worm tissues parallel with its development. We found that bacteria can enter into the embryos of C. elegans, a step associated with vitellogenin, and passed to the next generation. These vertically transmitted bacteria share global similarity, and bacterial distribution in worm tissues changes as they grow at different life stages. Antibiotic treatment of worms increased their vulnerability against pathogenic bacteria, and replenishment of tissue microbiota restored their immunity. These results not only offered a molecular basis of vertical transmission of bacteria in C. elegans, but also signal a new era for the mixed tissue cell-bacteria multi-species organism study.

physiology↗

bioRxiv2021

Single-cell metabolomics reveals the metabolic heterogeneity among microbial cells

In microbial research, the heterogeneity phenomenon is closely associated with microbial physiology in multiple dimensions. For now, A few studies were proposed in transcriptome and proteome analysis to discover the heterogeneity among single cells. However, microbial single cell metabolomics has not been possible yet. Herein, we developed a method, RespectM, based on discontinuous mass spectrometry imaging, which can detect more than 700 metabolites at a rate of 500 cells per hour. While ensuring the high throughput of RespectM, it integrates matrix sublimation, QC-based peak filtering, and batch correction strategies to improve accuracy. The results show that RespectM can distinguish single microbial cells from the blank matrix with an accuracy of 98.4%, depending on classification algorithms. Furthermore, to verify the accuracy of RespectM for distinguishing different single cells, we performed a classification test on Chlamydomonas reinhardtii single cells among allelic strains. The results showed an accuracy of 93.1%, which provides RespectM with enough confidence to perform microbial single cell metabolomics analysis. As we expected, untreated microbial cells will spontaneously undergo metabolic grouping coherence with genetic and biochemical similarities. Interestingly, the pseudo-time analysis also provided intuitive evidence on the metabolic dimension, indicating the cell grouping is based on microbial population heterogeneity. We believe that the RespectM can offer a powerful tool in the microbial study. Researchers can now directly analyze the changes in microbial metabolism at a single-cell level with high efficiency.

systems biology↗

bioRxiv2021

Multi-model Order ICA: A Data-driven Method for Evaluating Brain Functional Network Connectivity Within and Between Multiple Spatial Scales

BackgroundWhile functional connectivity is widely studied, there has been little work studying functional connectivity at different spatial scales. Likewise, the relationship of functional connectivity between spatial scales is unknown. MethodsWe proposed an independent component analysis (ICA) - based approach to capture information at multiple model orders (component numbers) and to evaluate functional network connectivity (FNC) both within and between model orders. We evaluated the approach by studying group differences in the context of a study of resting fMRI (rsfMRI) data collected from schizophrenia (SZ) individuals and healthy controls (HC). The predictive ability of FNC at multiple spatial scales was assessed using support vector machine (SVM)-based classification. ResultsIn addition to consistent predictive patterns at both multiple-model orders and single model orders, unique predictive information was seen at multiple-model orders and in the interaction between model orders. We observed that the FNC between model order 25 and 50 maintained the highest predictive information between HC and SZ. Results highlighted the predictive ability of the somatomotor and visual domains both within and between model orders compared to other functional domains. Also, subcortical-somatomotor, temporal-somatomotor, and temporal-subcortical FNCs had relatively high weights in predicting SZ. ConclusionsIn sum, multi-model order ICA provides a more comprehensive way to study FNC, produces meaningful and interesting results which are applicable to future studies. We shared the spatial templates from this work at different model orders to provide a reference for the community, which can be leveraged in regression-based or fully automated (spatially constrained) ICA approaches. Impact StatementMulti-model order ICA provides a comprehensive way to study brain functional network connectivity within and between multiple spatial scales, highlighting findings that would have been ignored in single model order analysis. This work expands upon and adds to the relatively new literature on resting fMRI-based classification and prediction. Results highlighted the differentiating power of specific intrinsic connectivity networks on classifying brain disorders of schizophrenia patients and healthy participants, at different spatial scales. The spatial templates from this work provide a reference for the community, which can be leveraged in regression-based or fully automated ICA approaches.

neuroscience↗

bioRxiv2021

Systematic dissection of a complex gut bacterial community

Efforts to model the gut microbiome have yielded important insights into the mechanisms of interspecies interactions, the impact of priority effects on ecosystem dynamics, and the role of diet and nutrient availability in determining community composition. However, the model communities studied to date have been defined or complex but not both, limiting their utility. Here, we construct a defined community of 104 bacterial strains composed of the most common taxa from the human gut microbiota. By propagating this community in growth media missing one amino acid at a time, we show that branched-chain amino acids have an outsize impact on community structure and identify a pathway in Clostridium sporogenes for generating ATP from arginine. We constructed and propagated the complete set of single-strain dropout communities, revealing a sparse network of strain-strain interactions including a novel interaction between C. sporogenes and Lactococcus lactis driven by metabolism. This work forms a foundation for studying strain-strain and strain-nutrient interactions in highly complex defined communities, and it provides a starting point for interrogating the rules of synthetic ecology at the 100+ strain scale.

microbiology↗

bioRxiv2021

In vivo augmentation of a complex gut bacterial community

Efforts to model the human gut microbiome in mice have led to important insights into the mechanisms of host-microbe interactions. However, the model communities studied to date have been defined or complex but not both, limiting their utility. In accompanying work, we constructed a complex synthetic community (104 strains, hCom1) containing the most common taxa in the human gut microbiome. Here, we used an iterative experimental process to improve hCom1 by filling open metabolic and/or anatomical niches. When we colonized germ-free mice with hCom1 and then challenged it with a human fecal sample, the consortium exhibited surprising stability; 89% of the cells and 58% of the taxa derive from the original community, and the pre- and post-challenge communities share a similar overall structure. We used these data to construct a second version of the community, adding 22 strains that engrafted following fecal challenge and omitting 7 that dropped out (119 strains, hCom2). In gnotobiotic mice, hCom2 exhibited increased stability to fecal challenge and robust colonization resistance against pathogenic Escherichia coli. Mice colonized by hCom2 versus human feces are similar in terms of microbiota-derived metabolites, immune cell profile, and bacterial density in the gut, suggesting that this consortium is a prototype of a model system for the human gut microbiome.

microbiology↗

bioRxiv2021

Systematic Analysis of Lysine Succinylation in Vero cells infected with Small Ruminant Morbillivirus

Small ruminant morbillivirus (SRMV), formerly named Peste-des-petits ruminants virus (PPRV), belongs to the genus Morbillivirus in the family Paramyxoviridae and causes a highly contagious disease in small ruminants, especially goats and sheep. Lysine succinylation is a newly identified and conserved modification and plays an important role in host cell response to pathogen infection. Here, we present a global analysis of the succinylome of SRMV-infected Vero cell using succinylation specific antibody-based enrichment and dimethylation labeling-based quantitative proteomics. As a result, 2633 succinylation sites derived from 823 cellular proteins were quantified. Comparative analysis revealed that 228 down-regulated succinylation sites on 139 proteins and 44 up-regulated succinylation sites on 38 proteins were significantly modified in response to SRMV infection, seven lysine succinylation motifs were identified. Bioinformatics analysis showed that the succinylated proteins mainly participated in cellular respiration and biosynthetic process. Protein-protein interaction networks of the identified proteins provided further evidence that a variety of ATP synthase subunits and carbon metabolism were modulated by succinylation while the overlapped proteins between succinylation and acetylation are involved in glyoxylate and dicarboxylate metabolism. Taken together, these findings provide the first report of succinylome in SRMV infection, lysine acetylation may have a more important effect than succinylation in SRMV infection. These findings provide a novel view on investigating the pathogenic mechanism of SRMV.

genomics↗