Biology subjects

Jiang, D.

Publications and source records attributed to Jiang, D..

At least 73 records · Page 4Linked to original sources

bioRxiv2023

Decoupling of evolutionary changes in mRNA and protein levels

Variation in gene expression across lineages is thought to explain much of the observed phenotypic variation and adaptation. The protein is closer to the target of natural selection but gene expression is typically measured as the amount of mRNA. The broad assumption that mRNA levels are good proxies for protein levels has been undermined by a number of studies reporting moderate or weak correlations between the two measures across species. One biological explanation for this discrepancy is that there has been compensatory evolution between the mRNA level and regulation of translation. However, we do not understand the evolutionary conditions necessary for this to occur nor the expected strength of the correlation between mRNA and protein levels. Here we develop a theoretical model for the coevolution of mRNA and protein levels and investigate the dynamics of the model over time. We find that compensatory evolution is widespread when there is stabilizing selection on the protein level, which is true across a variety of regulatory pathways. When the protein level is under directional selection, the mRNA level of a gene and its translation rate of the same gene were negatively correlated across lineages but positively correlated across genes. These findings help explain results from comparative studies of gene expression and potentially enable researchers to disentangle biological and statistical hypotheses for the mismatch between transcriptomic and proteomic studies.

evolutionary biology↗

bioRxiv2023

Infinite Physical Monkey: Do Deep Learning Methods Really Perform Better in Conformation Generation?

Conformation Generation is a fundamental problem in drug discovery and cheminformatics. Generally, it can be categorized into three different classes according to physical scales, i.e., micro molecule (organic), meso molecule (nano particle-like), and macro molecule (protein and nucleic acid). Organic molecule conformation generation, particularly in vacuum and protein pocket environments, is most relevant to drug design. Recently, with the development of geometric neural networks, the data-driven schemes have been successfully applied in this field, both for molecular conformation generation (in vacuum) and binding pose generation (in protein pocket). The former beats the traditional ETKDG method, while the latter achieves similar accuracy compared with the widely used molecular docking software. Although these methods have shown promising results for real-world drug design campaigns, some researchers have recently questioned whether deep learning (DL) methods perform better in molecular conformation generation via a "parameter-free" method. To our surprise, what they have designed is some kind analogous to the famous infinite monkey theorem, the monkeys that are even equipped with physics education. To discuss the feasibility of their proving, we constructed a real infinite stochastic monkey for molecular conformation generation, showing that even with a more stochastic sampler for geometry generation, the coverage of the benchmark QM-computed conformations are higher than those of most DL-based methods. By extending their physical monkey algorithm for binding pose prediction (with 2000 random samples), we also discover that the successful docking rate also achieves near-best performance among existing DL-based docking models. Thus, though their conclusions are right, their proof process needs more concern. In addition to evaluating the rationality of their algorithms and conclusions, we dig into the inspirations of infinite physical monkeys. We find that, for docking pose generation, DL-based models truly learn the interaction rules between residues and ligands, and discover an inductive bias hidden in the training of the pocket-given docking problem. The code of the proposed algorithm could be found at: https://github.com/HaotianZhangAI4Science/infinite-physical-monkey. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/531607v2_ufig1.gif" ALT="Figure 1"> View larger version (126K): org.highwire.dtl.DTLVardef@188ac2eorg.highwire.dtl.DTLVardef@1e006f3org.highwire.dtl.DTLVardef@e83f8forg.highwire.dtl.DTLVardef@1a4c7cd_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOTOC:C_FLOATNO Infinite Physical Monkey. This image was created with the assistance of DALL{middle dot}E 2 C_FIG

biophysics↗

bioRxiv2023

Structure of human NaV1.6 channel reveals Na+ selectivity and pore blockade by 4,9-anhydro-tetrodotoxin

The sodium channel NaV1.6 is widely expressed in neurons of the central and peripheral nervous systems, which plays a critical role in regulating neuronal excitability. Dysfunction of NaV1.6 has been linked to epileptic encephalopathy, intellectual disability and movement disorders. Here we present cryo-EM structures of human NaV1.6/{beta}1/{beta}2 alone and complexed with a guanidinium neurotoxin 4,9-anhydro-tetrodotoxin (4,9-ah-TTX), revealing molecular mechanism of NaV1.6 inhibition by the blocker. In the apo-form structure, two potential Na+ binding sites were revealed in the selectivity filter, suggesting a possible mechanism for Na+ selectivity and conductance. In the 4,9-ah-TTX-bound structure, 4,9-ah-TTX binds to a pocket similar to the tetrodotoxin (TTX) binding site, which occupies the Na+ binding sites and completely blocks the channel. Molecular dynamics simulation results show that subtle conformational differences in the selectivity filter affect the affinity of TTX analogues. Taken together, our results provide important insights into NaV1.6 structure, ion conductance, and inhibition.

biophysics↗

bioRxiv2023

Innate immune receptor C5aR1 regulates cancer cell fate and can be targeted to improve radiotherapy in tumours with immunosuppressive microenvironments

An immunosuppressive microenvironment causes poor tumour T-cell infiltration and is associated with reduced patient overall survival in colorectal cancer. How to improve treatment responses in these tumours is still a challenge. Using an integrated screening approach to identify cancer-specific vulnerabilities, we identify complement receptor C5aR1 as a druggable target which when inhibited improves radiotherapy even in tumours displaying immunosuppressive features and poor CD8+ T-cell infiltration. While C5aR1 is well-known for its role in the immune compartment, we find that C5aR1 is also robustly expressed on malignant epithelial cells, highlighting potential tumour-cell specific functions. C5aR1 targeting results in increased NF-{kappa}B-dependent apoptosis specifically in tumours and not normal tissues; indicating that in malignant cells, C5aR1 primarily regulates cell fate. Collectively, these data reveal that increased complement gene expression is part of the stress response mounted by irradiated tumours and that targeting C5aR1 can improve radiotherapy even in tumours displaying immunosuppressive features.

cancer biology↗

bioRxiv2023

Epigenetically silenced DACT3 promotes tumor growth via affecting Wnt/beta-catenin signaling and supports chidamide plus azacitidine therapy in acute myeloid leukemia

BackgroundDACT gene is a potential Wnt antagonist and tumor suppressor gene. However, the expression of DACT gene in acute myeloid leukemia (AML) and its role are still unknown. MethodsIn this study, we first multidimensionally analyzed the expression of DACT gene in AML through RNA seq, qRT-PCR and Western blotting analysis as well as TCGA database analysis. Then DACT3 was identified as playing a critical role in AML, and its clinical significance was further explored. The molecular mechanism of DACT3 down-regulation in AML from aspects of DNA methylation and histone acetylation were inquired. Finally, the biological functions of DACT3 in AML were investigated by cell models in vitro and animal experiments in vivo. ResultsCompared with DACT1 and DACT2, DACT3 was the most differentially expressed DACT family member in AML, suggesting that DACT3 plays the major role. The mRNA and protein expression levels of DACT3 were significantly decreased and positively correlated in AML. Moreover, low expression of DACT3 is associated with no remission disease status and poor prognosis in AML patients. In addition, down-regulation of DACT3 in AML was not completely dependent on promoter methylation, but also affected by histone deacetylation. We found that loss of DACT3 in AML is related to activation of Wnt signaling pathway. Furthermore, DACT3 inhibits the growth of AML cells in vitro and in severe immunodeficiency (SCID) mice. Importantly, DACT3 improved the sensitivity of adriamycin in treating AML cells. Further research showed that co-treatment of chidamide and azacytidine up-regulates DACT3 expression and promotes cell apoptosis via inhibiting Wnt/{beta}-catenin signaling in AML, suggesting a promising therapeutic prospects in FLT3-mutant AML. ConclusionThis is the first study revealing the epigenetic regulatory molecular mechanism of the down regulated expression of DACT3 in AML. Our data also shows that DACT3 is a candidate gene for therapeutic target and targeting DACT3 has the potential to validate the combination therapy of DNMT inhibitors and HDAC inhibitors.

molecular biology↗

bioRxiv2022

The protist ubiquitin ligase effector PbE3-2 targets RD21A to impede plant immunity

Clubroot caused by the soil-borne protist pathogen Plasmodiophora brassicae is one of the most devastating diseases of Brassica oil and vegetable crops worldwide. Understanding the pathogen infection strategy is crucial for the development of disease control. However, the molecular mechanism by which this pathogen promotes infection remains largely unknown. Here, we identified a P. brassicae-secreted effector PbE3-2 that impedes plant immunity by ubiquitinating the immune regulator RD21A for degradation. Overexpression of PbE3-2 in Arabidopsis thaliana resulted in higher susceptibility to P. brassicae and decreases in chitin-triggered reactive oxygen species burst and expression of marker genes in salicylic acid signaling. PbE3-2 interacted with and ubiquitinated RD21A in vitro and in vivo. Mutant plants deficient in RD21A exhibited similar susceptibility and compromsied immune responses as in PbE3-2 overexpression plants. These results suggest that P. brassicae promotes clubroot disease through RD21A degradation mediated by the effector PbE3-2. As PbE3-2 is widely conserved across different P. brassicae pathotypes, the degradation of RD21A by PbE3-2 might be a prevalent infection strategy in this pathogen.

microbiology↗

bioRxiv2022

A high potent synthetic nanobody with broad-spectrum activity neutralizes SARS-Cov-2 virus and Omicron variant through a unique binding mode

The major challenge to control COVID pandemic is the rapid mutation rate of the SARS-Cov-2 virus, leading to the escape of the protection of vaccines and most of the neutralizing antibodies to date. Thus, it is essential to develop neutralizing antibodies with broad-spectrum activity targeting multiple SARS-Cov-2 variants. Here, we reported a synthetic nanobody (named C5G2) obtianed by phage display and subsequent antibody engineering. C5G2 has a single digit nanomolar binding affinity to RBD domain and inhibits its binding to ACE2 with an IC50 of 3.7 nM. Pseudovirus assay indicated that the monovalent C5G2 could protect the cells from the infection of SARS-Cov-2 wild type virus and most of the virus of concern, i.e. Alpha, Beta, Gamma and Omicron variants. Strikingly, C5G2 has the highest potency against Omicron among all the variants with the IC50 of 4.9ng/mL. The Cryo-EM structure of C5G2 in complex with the Spike trimer showed that C5G2 bind to RBD mainly through its CDR3 at a conserved region that not overlapping with the ACE2 binding surface. Additionally, C5G2 bind simultaneously to the neighboring NTD domain of spike trimer through the same CDR3 loop, which may further increase its potency against the virus infection. Third, the steric hindrance caused by FR2 of C5G2 could inhibit the binding of ACE2 to RBD as well. Thus, this triple-function nanobody may be served as an effective drug for the prophylaxis and therapy against Omicron as well as future variants.

biochemistry↗

bioRxiv2022

Tyrosine phosphorylation tunes chemical and thermal sensitivity of TRPV2 ion channel

Transient receptor potential vanilloid 2 (TRPV2) is a multimodal ion channel widely regulating central and peripheral functions. Its important involvement in immune responses has been suggested such as in the macrophages phagocytosis process. However, the endogenous signaling cascades controlling the gating of TRPV2 remain to be understood. Here, we report that enhancing tyrosine phosphorylation remarkably alters the chemical and thermal sensitivities of TRPV2 endogenously expressed in rat bone marrow-derived macrophages. We identify that the protein tyrosine kinase JAK1 mediates TRPV2 phosphorylation at the molecular sites Tyr(335), Tyr(471), and Tyr(525). JAK1 phosphorylation is required for maintaining TRPV2 activity and the phagocytic ability of macrophages. We further show that TRPV2 phosphorylation is dynamically balanced by protein tyrosine phosphatase non-receptor type 1 (PTPN1). PTPN1 inhibition increases TRPV2 phosphorylation, further reducing the activation temperature threshold to [~]40 {degrees}C. Our data thus unveil an intrinsic mechanism where the phosphorylation/dephosphorylation dynamic balance sets the basal chemical and thermal sensitivity of TRPV2. Targeting this pathway will aid therapeutic interventions in physiopathological contexts.

physiology↗

bioRxiv2021

Fine mapping of goat polledness variant in six Chinese native breeds

BackgroundThe genetic mechanism of goat polledness has been studied for decades, but identifying causative variants and functional genes remains challenging. ResultsUsing a genome-wide association study (GWAS), we identified a significant striking locus for polledness in two different goat breeds. To reduce the linkage disequilibrium among variants for localizing causative variants in the finer region, we sequenced 79 goats from six Chinese native breeds (Jining Gray, Matou, Guizhou black, Yunnan black bone, Chaidamu, and Ujumqin) and identified 483.5 kb CNV (150,334,567-150,818,099) translocated into the previously identified 11.7 kb polled intersex syndrome region, which was consistent with previous research using intersex goat populations. Within the 483.5 kb CNV, a ~322 bp horn-specific element, similar to the superfamily of tRNA-derived families of SINEs, located at the first intron of the ERG gene was identified. The results of the GO enrichment analysis showed that the Horn-SINE element-associated genes were involved in both nervous system and head development. Finally, we used RNA sequencing to investigate gene expression profiles in the horn bud and skin tissues of horned and polled goats. We identified 1077 and 1222 differentially expressed genes between the horn bud and skin tissue in polled and horned goats, respectively. We also identified 367 differentially expressed genes in horn buds between polled and horned animals, and found that the two CNV-related genes, ERG and FOXL2, were upregulated in the horn bud of polled goats. Gene functional enrichment analysis demonstrated that the downregulated genes in the horn bud of polled goats were enriched in skeletal system development, whereas the upregulated genes were significantly overexpressed in muscle tissue development. ConclusionsBroadly, this study describes a novel structural variant responsible for polledness/intersex traits and contributes to the discovery of molecular mechanisms underlying the development and regulation of the polledness trait.

genetics↗

bioRxiv2021

Coral larvae suppress the heat stress response during the onset of symbiosis thereby decreasing their odds of survival

The endosymbiosis between most corals and their photosynthetic dinoflagellate partners begins early in the host life history, when corals are larvae or juvenile polyps. The capacity of coral larvae to buffer climate-induced stress while in the process of symbiont acquisition could come with physiological trade-offs that alter larval behavior, development, settlement and survivorship. Here we examined the joint effects of thermal stress and symbiosis onset on colonization dynamics, survival, metamorphosis and host gene expression of Acropora digitifera larvae. We found that thermal stress decreased symbiont colonization of hosts by 50% and symbiont density by 98.5% over two weeks. Temperature and colonization also influenced larval survival and metamorphosis in an additive manner, where colonized larvae fared worse or prematurely metamorphosed more often than non-colonized larvae under thermal stress. Transcriptomic responses to colonization and thermal stress treatments were largely independent, while the interaction of these treatments revealed contrasting expression profiles of genes that function in the stress response, immunity, inflammation and cell cycle regulation. The combined treatment either canceled or lowered the magnitude of expression of heat-stress responsive genes in the presence of symbionts, revealing a physiological cost to acquiring symbionts at the larval stage with elevated temperatures. In addition, host immune suppression, a hallmark of symbiosis onset under ambient temperature, turned to immune activation under heat stress. Thus, by integrating the physical environment and biotic pressures that mediate pre-settlement event in corals, our results suggest that colonization may hinder larval survival and recruitment creating isolated, genetically similar populations under projected climate scenarios.

ecology↗

bioRxiv2021

Whole-genome sequencing of Chinese native goat offers biological insights into cashmere fiber formation

Cashmere evolved naturally in the goat, and almost all breeds of goat can produce more or less cashmere fibers. However, the genetic alterations underlying cashmere trait selection are still unclear.We sequenced 120 Chinese native goat including two cashmere goat breeds (Ujumain, Chaidamu) and six ordinary goat breeds (Jining Gray, Matou, Guizhou Black, Jintang Black, Yunnan Black Bone, Chengdu Brown). The genome-wide selective sweep of cashmere goat and ordinary goat revealed a novel set of candidate genes as well as pathways, such as Nuclear factor kappa-B and Wnt Signaling pathways. Of them, the LHX2 gene regulating hair follicle development, was evident from the strongest selection signal when comparing the Uhumqin cashmere goat and ordinary goat. Interestingly, we identified a 582bp deletion at 367 kb upstream of LHX2 with higher frequency in cashmere goats and their ancient relatives. This mutation probably rises along the breeding procedures, and is putatively responsible for cashmere production and diameter, as revealed by association studies. Luciferase assay shows that the deletion, which acts as an insulator, restrains the expression of LHX2 by interfering its upstream enhancers.Our study discovers a novel insulator of the LHX2 involved in regulating cashmere production and diameter, which would be beneficial to understanding hair follicle development and regeneration. Our findings also provide new insights into the genetic formation of cashmere, and facilitate subsequent molecular breeding for cashmere goat improvement.

genomics↗

bioRxiv2021

Aldehyde dehydrogenase 3A1 deficiency leads to mitochondrial dysfunction and impacts salivary gland stem cell self-renewal, differentiation and survival

Adult salivary stem/progenitor cells (SSPC) have an intrinsic property to self-renew in order to maintain tissue architecture and homeostasis. Adult salivary glands have been documented to harbor SSPC, which have been shown to play a vital role in the regeneration of the glandular structures post radiation damage. We have previously demonstrated that activation of aldehyde dehydrogenase 3A1 (ALDH3A1) after radiation reduced aldehyde accumulation in SSPC, leading to less apoptosis and improved salivary function. We subsequently found that sustained pharmacological ALDH3A1 activation is critical to enhance regeneration of murine submandibular gland after radiation damage. Further investigation shows that ALDH3A1 function is crucial for SSPC self-renewal and differentiation even in the absence of radiation stress. Salivary glands from Aldh3a1-null mice have fewer acinar structures than wildtype mice. ALDH3A1 deletion or pharmacological inhibition in SSPC leads to a decrease in mitochondrial DNA copy number, lower expression of mitochondrial specific genes and proteins, structural abnormalities, lower membrane potential, and reduced cellular respiration. Loss or inhibition of ALDH3A1 also elevates ROS levels and accumulation of ALDH3A1 substrate 4-hydroxynonenal (4-HNE, a lipid peroxidation product), leading to decreased survival of murine SSPC that can be rescued by treatment with 4-HNE specific carbonyl scavengers. Our data indicate that ALDH3A1 activity protects mitochondrial function and is important for the development and regeneration activity of SSPC. This knowledge will help to guide our translational strategy of applying ALDH3A1 activators in the clinic to prevent radiation-related hyposalivation in head and neck cancer patients.

cell biology↗

bioRxiv2021

A positively Tuned Voltage Indicator Reveals Electrical Correlates of Calcium Activity in the Brain

Neuronal spiking activity is routinely recorded using genetically encoded calcium indicators (GECIs), but calcium imaging is limited in temporal resolution and does not report subthreshold voltage changes. Genetically encoded voltage indicators (GEVIs) offer better temporal resolution and subthreshold sensitivity, but spike detection with fast GEVIs has required specialized imaging equipment. Here, we report the ASAP4 subfamily of genetically encoded voltage indicators (GEVIs) that brighten in response to membrane depolarization, inverting the fluorescence-voltage relationship of previous ASAP GEVIs. Two variants, ASAP4b and ASAP4e, feature 128% and 178% fluorescence increases over 100-mV of depolarization, respectively, facilitating spike detection in single trials in vivo with standard 1 and 2-photon imaging systems. Simultaneous voltage and calcium imaging confirms improved temporal resolution and spike discernment by ASAP4 GEVIs. Thus, positively tuned ASAP4 voltage indicators enable recording of neuronal spiking activity using similar equipment as calcium imaging, while providing higher temporal resolution. One Sentence SummaryUpward ASAPs increase detection capability of GEVIs in vivo.

neuroscience↗

bioRxiv2021

Rapid 3D-STORM imaging of diverse molecular targets in tissue

The precise organization of fine scale molecular architecture is critical for the nervous system and other biological functions and would benefit from nanoscopic imaging methods with improved accessibility, throughput, and native tissue compatibility. Here, we report RAIN-STORM, a rapid and scalable imaging approach that enables three-dimensional nanoscale target visualization for multiple subcellular and intracellular targets within tissue at depth. RAIN-STORM utilizes conventional tissue samples, readily available reagents in optimized formulas, requires no specialized sample handling, and is suitable for commercial instrumentation. To illustrate RAIN-STORMs ability for quantitative high-resolution nanoscopic tissue imaging, we utilized the well-organized but structurally complex retina. We show that RAIN-STORM is rapid and versatile, enabling 3D nanoscopic imaging of over 20 distinct targets to reveal known and novel nanoscale features of synapses, neurons, glia, and vascular. Further, imaging parameters are compatible with a wide range of tissue sources and molecular targets across a spectrum of biological structures. Finally, we show that this method can be applied to clinically derived samples and reveal the nanoscale distribution of molecular targets within human samples. RAIN-STORM thus enables rapid 3D imaging for a range of molecules, paving the way for high throughput studies of nanoscopic molecular features in intact tissue from diverse sources.

neuroscience↗

bioRxiv2021

Botrytis cinerea BcPTP1 is a late infection phase, cysteine rich protein cytotoxic effector

Botrytis cinerea is a broad-host-range necrotrophic phytopathogen responsible for serious crops diseases. To facilitate infection, B. cinerea secretes a large number of effectors that induce plant cell death. In screening secretome data of B. cinerea during infection stage, we identified a phytotoxic protein (BcPTP1) that can also induce immune resistance in plants. BcPTP1 is a small (90 aa), cysteine rich protein without any known domains. Transiently expression of BcPTP1 in leaves caused chlorosis that intensifies with time and eventually lead to cell death. Point mutations in eight of the 10 cysteine residues of BcPTP1 abolished the toxic effect, however residual toxic activity remained after heating the peptide, suggesting contribution of unknown epitopes to protein phytotoxic effect. The transcript level of the bcptp1 gene was low during the first 36 h after inoculation and increased sharply upon transition to the late infection stage, suggesting a role of BcPTP1 in lesion spreading. While statistically insignificant, deletion of the bcptp1 gene led to slightly smaller lesions on bean leaves. Further analyses indicated that BcPTP1 is internalized into plant cells after secreting into the apoplast and its phytotoxic effect is negatively regulated by the receptor-like kinases BAK1 and SOBIR1. Collectively, our findings show that BcPTP1 is a virulence factor that toxifies the host cells and facilitates lesion spreading during the late infection stage.

pathology↗

bioRxiv2021

Gating mechanism of human N-type voltage-gated calcium channel

N-type voltage-gated calcium (CaV) channels mediate Ca2+ influx at the presynaptic terminals in response to action potential and play vital roles in synaptogenesis, neurotransmitter releasing, and nociceptive transmission. Here we elucidate a cryo-electron microscopy (cryo-EM) structure of the human CaV2.2 complex at resolution of 2.8 [A]. This complex structure reveals how the CaV2.2, {beta}1, and 2{delta}1 subunits are assembled. In our structure, the second voltage-sensing domain (VSD) is stabilized at a resting-state conformation, which is distinct from the other three VSDs of CaV2.2 as well as activated VSDs observed in previous structures of CaV channels. The structure also shows that the intracellular gate formed by S6 helices is closed, and a W-helix from the DII-III linker is determined to act as a blocking-ball that causes closed-state inactivation in CaV2.2. Collectively, our structure provides previously unseen structural insights into fundamental gating mechanisms of CaV channels.

neuroscience↗

bioRxiv2021

The REF6-dependent H3K27 demethylation establishes transcriptional competence to promote germination in Arabidopsis

Seed germination is a critical developmental switch from a dormant state to active growth, which involves extensive changes in metabolism, gene expression and cellular identity. However, our understanding of epigenetic and transcriptional reprogramming during this process is limited. The histone H3 lysine 27 trimethylation (H3K27me3) plays a key role in regulating gene repression and cell fate specification. Here, we profile H3K27me3 dynamics and dissect the function of H3K27 demethylation during germination. Our temporal genome-wide profiling of H3K27me3 and transcription reveal delayed H3K27me3 reprogramming compared with transcriptomic changes during germination, with H3K27me3 changes mainly occurring when the embryo is entering into vegetative development. REF6-mediated H3K27 demethylation promotes germination but does not significantly contribute to H3K27me3 dynamics during germination, but rather stably establishes an H3K27me3-depleted state permissive to transcription. By analyzing REF6 genomic binding, we show that it is absent from mature embryo chromatin and gradually establishes occupancy during the course of germination to counteract increased PRC2 activity. Our study provides key insights into the dynamics of gene expression and H3K27me3 during seed germination and suggests the function of H3K27me3 in facilitating cell fate switch. Furthermore, we reveal the importance of H3K27 demethylation-established transcriptional competence in germination and likely other developmental processes.

plant biology↗

bioRxiv2021

AutoVEM2: a flexible automated tool to analyze candidate key mutations and epidemic trends for virus

In our previous work, we developed an automated tool, AutoVEM, for real-time monitoring the candidate key mutations and epidemic trends of SARS-CoV-2. In this research, we further developed AutoVEM into AutoVEM2. AutoVEM2 is composed of three modules, including call module, analysis module, and plot module, which can be used modularly or as a whole for any virus, as long as the corresponding reference genome is provided. Therefore, its much more flexible than AutoVEM. Here, we analyzed three existing viruses by AutoVEM2, including SARS-CoV-2, HBV and HPV-16, to show the functions, effectiveness and flexibility of AutoVEM2. We found that the N501Y locus was almost completely linked to the other 16 loci in SARS-CoV-2 genomes from the UK and Europe. Among the 17 loci, 5 loci were on the S protein and all of the five mutations cause amino acid changes, which may influence the epidemic traits of SARS-CoV-2. And some candidate key mutations of HBV and HPV-16, including T350G of HPV-16 and C659T of HBV, were detected. In brief, we developed a flexible automated tool to analyze candidate key mutations and epidemic trends for any virus, which would become a standard process for virus analysis based on genome sequences in the future. HighlightsO_LIAn automatic tool to quickly analyze candidate key mutations and epidemic trends for any virus was developed. C_LIO_LIOur integrated analysis method and tool could become a standard process for virus mutation and epidemic trend analysis based on genome sequences in the future. C_LIO_LIN501Y with the other 16 highly linked mutation sites of SARS-CoV-2 in the UK and Europe were further confirmed, and some valuable mutation sites of HBV and HPV-16 were detected. C_LI

genomics↗