SIRT4 Has an Anti-Cancer Role in Cervical Cancer by Inhibiting Glutamine Metabolism via the MEK/ERK/C-Myc Axis.

BACKGROUND/AIM: Glutamine metabolism is crucial in cell proliferation, aging, and apoptosis across various cancer types. Existing research indicates that Sirtuin 4 (SIRT4), primarily located in mitochondria, modulates this process. This study aimed to clarify the regulatory relationship between SIRT4 and glutamine metabolism in cervical cancer. MATERIALS AND METHODS: SIRT4 mRNA levels and their clinical correlation to cervical cancer were analyzed using the UALCAN database. Immunohistochemistry (IHC) was performed to assess SIRT4 protein expression in tissue samples from cervical cancer patients. Transient transfection was employed to create Hela and Siha cell lines with overexpressed SIRT4, mitogen-activated extracellular signal-regulated kinase (MEK), and glutaminase 1 (GLS1). The impact on cellular functions was studied using MTT, soft agar, transwell, and western blotting assays. Glutamate and ATP levels were also measured to evaluate metabolic changes. RESULTS: Low levels of SIRT4 mRNA in cervical cancer tissues correlated with tumor metastasis and poor survival rates. Overexpression of SIRT4 led to suppressed cell proliferation, colony growth, and motility, along with significant down-regulation of GLS expression, a key contributor to glutamine metabolism. Additionally, SIRT4 overexpression resulted in the inactivation of the MEK/ERK/c-myc signaling pathway, while overexpression of MEK reversed these effects. Notably, the inhibitory effects of SIRT4 on cell proliferation, colony formation, migration, and invasion in Hela and Siha cells were significantly attenuated following GLS1 overexpression. CONCLUSION: SIRT4 acts as an anti-cancer agent in cervical cancer by inhibiting glutamine metabolism through the MEK/ERK/c-myc signaling pathway, providing a novel sight for cervical cancer therapy.

Toward Accurate Quantum Mechanical Thermochemistry: (1) Extensible Implementation and Comparison of Bond Additivity Corrections and Isodesmic Reactions.

Obtaining accurate enthalpies of formation of chemical species, ΔHf, often requires empirical corrections that connect the results of quantum mechanical (QM) calculations with the experimental enthalpies of elements in their standard state. One approach is to use atomization energy corrections followed by bond additivity corrections (BACs), such as those defined by Petersson et al. or Anantharaman and Melius. Another approach is to utilize isodesmic reactions (IDRs) as shown by Buerger et al. We implement both approaches in Arkane, an open-source software that can calculate species thermochemistry using results from various QM software packages. In this work, we collect 421 reference species from the literature to derive ΔHf corrections and fit atomization energy corrections and BACs for 15 commonly used model chemistries. We find that both types of BACs yield similar accuracy, although Anantharaman- and Melius-type BACs appear to generalize better. Furthermore, BACs tend to achieve better accuracy than IDRs for commonly used model chemistries, and IDRs can be less robust because of the sensitivity to the chosen reference species and reactions. Overall, Anantharaman- and Melius-type BACs are our recommended approach for achieving accurate QM corrections for enthalpies.

Changes in serum inflammatory factors in group B streptococcal infection and their predictive value for premature rupture of membranes complicated by chorioamnionitis.

Objective: The aim of this study as to unveil changes in serum inflammatory factors in pregnant women with genital tract group B Streptococcus (GBS) infection and their predictive value for premature rupture of membranes (PROM) complicated by chorioamnionitis (CS) and adverse pregnancy outcomes. Methods: The value of serum inflammatory factor levels in predicting PROM complicating CS and adverse pregnancy outcomes in GBS-infected pregnant women was evaluated by ELISA. Results: Serum IL-6, TNF-α, PCT and hs-CRP levels were higher in pregnant women with GBS infection. The combined diagnosis of these factors had excellent diagnostic value in PROM complicating CS and adverse pregnancy outcomes. Conclusion: Joint prediction of IL-6, TNF-α, PCT and hs-CRP has the best predictive value for PROM complicating CS and adverse pregnancy outcomes.

[Box: see text].

Improved structure stability and performance of a LiFeSO4F cathode material for lithium-ion batteries by magnesium substitution.

Tavorite LiFeSO4F with high Li-ion conductivity has been considered a promising alternative to LiFePO4. However, its poor cycle stability and low electronic conductivity limit the practical application of Tavorite LiFeSO4F. In the present study, we employ a solvothermal method to produce magnesium-substitution LiMgxFe1-xSO4F (x = 0, 0.02, 0.04) cathode materials in which the Mg substitutes the Fe(2) sites. The first-principles calculations demonstrate that Mg-substitution could reduce the bandgap of LiFeSO4F and increase its electronic conductivity to 2.5 × 10-11 S cm-1. Meanwhile, CI-NEB and BV calculations reveal that the diffusion energy barrier of lithium along the (100) direction after Mg substitution is lower than the pristine sample, and the electrochemical inactive Mg2+ could improve the structure stability. The results show that the Mg-substituted LiFeSO4F exhibits enhanced cycle stability and rate performance compared with the pristine LiFeSO4F, suggesting that the use of electrochemically inactive ion substitution may be critical for the development of high-performance LiFeSO4F cathode materials for lithium-ion batteries.

PPanG: a precision pangenome browser enabling nucleotide-level analysis of genomic variations in individual genomes and their graph-based pangenome.

Graph-based pangenome is gaining more popularity than linear pangenome because it stores more comprehensive information of variations. However, traditional linear genome browser has its own advantages, especially the tremendous resources accumulated historically. With the fast-growing number of individual genomes and their annotations available, the demand for a genome browser to visualize genome annotation for many individuals together with a graph-based pangenome is getting higher and higher. Here we report a new pangenome browser PPanG, a precise pangenome browser enabling nucleotide-level comparison of individual genome annotations together with a graph-based pangenome. Nine rice genomes with annotations were provided by default as potential references, and any individual genome can be selected as the reference. Our pangenome browser provides unprecedented insights on genome variations at different levels from base to gene, and reveals how the structures of a gene could differ for individuals. PPanG can be applied to any species with multiple individual genomes available and it is available at https://cgm.sjtu.edu.cn/PPanG .

Subgraph Isomorphic Decision Tree to Predict Radical Thermochemistry with Bounded Uncertainty Estimation.

Detailed chemical kinetic models offer valuable mechanistic insights into industrial applications. Automatic generation of reliable kinetic models requires fast and accurate radical thermochemistry estimation. Kineticists often prefer hydrogen bond increment (HBI) corrections from a closed-shell molecule to the corresponding radical for their interpretability, physical meaning, and facilitation of error cancellation as a relative quantity. Tree estimators, used due to limited data, currently rely on expert knowledge and manual construction, posing challenges in maintenance and improvement. In this work, we extend the subgraph isomorphic decision tree (SIDT) algorithm originally developed for rate estimation to estimate HBI corrections. We introduce a physics-aware splitting criterion, explore a bounded weighted uncertainty estimation method, and evaluate aleatoric uncertainty-based and model variance reduction-based prepruning methods. Moreover, we compile a data set of thermochemical parameters for 2210 radicals involving C, O, N, and H based on quantum chemical calculations from recently published works. We leverage the collected data set to train the SIDT model. Compared to existing empirical tree estimators, the SIDT model (1) offers an automatic approach to generating and extending the tree estimator for thermochemistry, (2) has better accuracy and R2, (3) provides significantly more realistic uncertainty estimates, and (4) has a tree structure much more advantageous in descent speed. Overall, the SIDT estimator marks a great leap in kinetic modeling, offering more precise, reliable, and scalable predictions for radical thermochemistry.

Chitosan-initiated gold nanoparticles with enhanced fluorescence for unique Fe3+/PPi sensing and photothermal therapy.

The design of surface ligands is crucial for ligand-protected gold nanoparticles (AuNPs). Herein, following the principle of green synthesis, environmentally friendly gold nanoparticles (AuNPs@His@CC, AuHC) were fabricated based on dual ligands of histidine and carboxylated chitosan. AuHC showed the advantages of low toxicity, good photoluminescent stability and ideal biocompatibility. Compared with single histidine-coated gold nanoclusters (AuNCs@His, AuH), AuHC presented enhanced fluorescence attributed to the addition of chitosan. The blue-emitting AuHC has a unique response to Fe3+ with detection limits as low as 9.51 nM. Interestingly, the quenched fluorescence of AuHC-Fe3+ system could be restored through the introduction of PPi with a detection limit of 10.6 µM. So an "on-off-on" fluorescence sensing platform was achieved. Apart from good optical properties and sensing, the designed AuHC demonstrated outstanding photothermal conversion efficiency (27.8 %), which made it ideal material for thermal ablation of tumor. To be specific, after laser irradiation (660 nm, 0.78 W cm-2, 10 min) of AuHC, the survival rate of HeLa cells as a tumor cell model decreased to 12.7 %, indicating that AuHC has a significant tumor inhibition effect in vitro. Besides, AuHC also could be a befitting candidate for overcoming drug-resistant tumor cells such as MCF-7/ADR cells. Notably, AuHC can markedly ablate solid tumors in 4T1 tumor-bearing mice after laser irradiation (660 nm, 0.78 W cm-2, 10 min). Hence this work provides insight into the design of multifunctional AuNPs platform for simultaneously integrating the ion sensing and photothermal therapy of cancer.

Detection of Antibiotic Resistance and Analysis of Resistance Genes and Virulence Genes of Salmonella Isolated from Human.

Salmonella is a food-borne pathogen that can cause zoonoses. The emergence of drug-resistant strains of Salmonella is of great concern. It is necessary to understand the prevalence of antibiotic resistance, antibiotic resistance genes and virulence genes in human Salmonella. In this study, drug susceptibility test was used to detect and analyze the drug resistance of 24 Salmonella strains collected from human. A multi-drug resistant strain QLUF123 was selected for whole genome sequencing, and its drug resistance genes and virulence genes were analyzed. The results showed that 24 Salmonella strains were resistant to the tested antibiotics, 87.50% of the strains had multi-drug resistance, the resistance rate to ceftazidime, sulfamethoxazole and tilmicosin reached more than 80%. The alignment results based on the whole genome sequence showed that there were multiple types of drug-resistant genes in QLUF123, among which efflux pump system genes were the most abundant, including sdiA, mdtK, baeR and other multidrug-resistant efflux pump system genes. QLUF123 carried 46 kinds of virulence factors and 249 related virulence genes, among which the three functions of secretory system, adhesion and motility accounted for the most virulence genes, accounting for 93.57%. In this study, antibiotic resistance of human Salmonella was detected by drug sensitivity test, and drug resistance and virulence genes in Salmonella were analyzed by whole genome sequencing technology, which is of great significance for scientific treatment and rational drug use of related diseases caused by Salmonella infection.

Effect of polyene phosphatidylcholine/ursodeoxycholic acid/ademetionine on pregnancy outcomes in intrahepatic cholestasis.

BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) is a liver disorder that occurs in pregnant women and can lead to a range of adverse pregnancy outcomes. The condition is typically marked by pruritus (itching) and elevated levels of liver enzymes and bile acids. The standard treatment for ICP has generally been ursodeoxycholic acid and ademetionine 1,4-butanedisulfonate, but the efficacy of this approach remains less than optimal. Recently, polyene phosphatidylcholine has emerged as a promising new therapeutic agent for ICP due to its potential hepatoprotective effects. AIM: To evaluate the effect of polyene phosphatidylcholine/ursodeoxycholic acid/ ademetionine 1,4-butanedisulfonate on bile acid levels, liver enzyme indices, and pregnancy outcomes in patients with ICP. METHODS: From June 2020 to June 2021, 600 patients with ICP who were diagnosed and treated at our hospital were recruited and assigned at a ratio of 1:1 via random-number table method to receive either ursodeoxycholic acid/ademetionine 1,4-butanedisulfonate (control group, n = 300) or polyene phosphatidylcholine/ursodeoxycholic acid/ademetionine 1,4-butanedisulfonate (combined group, n = 300). Outcome measures included bile acids levels, liver enzyme indices, and pregnancy outcomes. RESULTS: Prior to treatment, no significant differences were observed between the two groups (P > 0.05). Post-treatment, patients in both groups had significantly lower pruritus scores, but the triple-drug combination group had lower scores than the dual-drug combination group (P < 0.05). The bile acid levels decreased significantly in both groups, but the decrease was more significant in the triple-drug group (P < 0.05). The triple-drug group also exhibited a greater reduction in the levels of certain liver enzymes and a lower incidence of adverse pregnancy outcomes compared to the dual-drug group (P < 0.05). CONCLUSION: Polyene phosphatidylcholine/ursodeoxycholic acid/ademetionine 1,4-butanedisulfonate effectively relieves pruritus and reduces bile acid levels and liver enzyme indices in patients with ICP, providing a positive impact on pregnancy outcome and a high safety profile. Further clinical trials are required prior to clinical application.

Genomic typing and virulence gene profile analysis of Salmonella Derby from different sources.

Salmonella enterica serovar Derby (S. Derby) is one of the most common Salmonella serovars which can infect poultry, swine, and humans. With the reduction of the sequencing cost and the improvement of sequencing technology, whole genome sequencing (WGS) has become an important method for bacterial determination, molecular investigation, and pathogenic tracing analysis. In this study, we investigated S. Derby isolates from different sources in China using in-silico multilocus sequence typing (MLST), core genome MLST (cgMLST) and whole genome MLST (wgMLST) analysis based on WGS. The results showed that 21 S. Derby strains were divided into 3 STs using MLST analysis, including ST40 (n = 19, accounting for 90.48%), ST71 (n = 1, accounting for 4.76%) and ST8016 (n = 1, accounting for 4.76%). cgMLST and wgMLST analysis categorized the tested strains into 13 cgSTs and 21 wgSTs, respectively. The minimum spanning trees of cgMLST and wgMLST both divided these strains into 3 clusters and 4 singletons. In addition, virulence gene profiles of S. Derby isolates were also analyzed, and a total of 174 virulence genes belonged to 8 categories were identified. In summary, we studied genomic typing, phylogenetic relationship and virulence gene profiles of S. Derby strains from different sources in China. These findings were beneficial for the epidemiology and pathogenesis of Salmonella.

Biofilm-forming ability of Salmonella enterica strains of different serotypes isolated from multiple sources in China.

Salmonella is an important zoonotic and foodborne pathogen that can infect humans and animals, causing severe concerns about food safety and a heavy financial burden worldwide. The pathogen can adhere to living and abiotic surfaces by forming biofilms, which increases the risk of transmission and infection. In this study, we investigated the biofilm-forming ability of 243 Salmonella strains of 36 serotypes from different sources in China using microplate crystal violet staining method. The results showed that 99.6% tested strains, with the exception of one strain of S. Thompson, were capable of forming biofilms. The strains with the biofilm-forming ability of strong, medium and weak accounted for 2.88%, 24.28% and 72.43%, respectively. The strains of S. Havana and S. Hvittingfoss had the strongest biofilm-forming ability, with the OD570 of 0.81 ± 0.02 and 0.81 ± 0.38, respectively, while the strains of S. Agona and S. Bovismorbificans had the weakest biofilm-forming ability, with the OD570 of 0.16 ± 0.02 and 0.15 ± 0.00, respectively. Furthermore, statistical analysis results demonstrated that isolation of source had no effect on the biofilm formation ability, while the detection rates of pefABCD and ddhC were positively correlated with the biofilm formation ability of Salmonella. In particular, the detection rate of ddhC gene was more than 60% in the biofilm forming strains. These findings have important guiding significance for the investigation of pathogenesis, as well as the prevention and control of salmonellosis.

Insights into the genetic determination of tuber shape and eye depth in potato natural population based on autotetraploid potato genome.

Potato is one of the world's most important food crops, with a time-consuming breeding process. In this study, we performed a genome-wide association (GWAS) analysis of the two important traits of potato tuber shape and eye depth, using the tetraploid potato genome (2n=4x=48) as a reference. A total of 370 potatoes were divided into three subgroups based on the principal component analysis and evolutionary tree analysis. The genetic diversity within subgroups is low (5.18×10-5, 4.36×10-5 and 4.24×10-5). Genome-wide linkage disequilibrium (LD) analysis showed that their LD is about 60 Kb. GWAS analysis identified that 146 significant single nucleotide polymorphism (SNP) loci at Chr01A1:34.44-35.25 Mb and Chr02A1:28.35-28.54 Mb regions are significantly associated with potato tuber shape, and that three candidate genes that might be related to potato tuber traits, PLATZ transcription factor, UTP-glucose-1-phosphate uridylyltransferase and FAR1 DNA-binding domain, are in the association region of Chr02A1. GWAS analysis identified 53 significant SNP loci at Chr05A2: 49.644-50.146 Mb and Chr06A2: 25.866-26.384 Mb regions with robust associations with potato tuber eye depth. Hydrolase and methyltransferases are present in the association region of Chr05A2, and three CYPs are present in the association region of Chr06A2. Our findings suggested that these genes are closely associated with potato tuber shape and eye depth. Our study identified molecular markers and candidate genes for improving tetraploid potato tuber shape and eye depth and provided ideas and insights for tetraploid potato breeding.

Butyl Acetate Pyrolysis and Combustion Chemistry: Mechanism Generation and Shock Tube Experiments.

The combustion and pyrolysis behaviors of light esters and fatty acid methyl esters have been widely studied due to their relevance as biofuel and fuel additives. However, a knowledge gap exists for midsize alkyl acetates, especially ones with long alkoxyl groups. Butyl acetate, in particular, is a promising biofuel with its economic and robust production possibilities and ability to enhance blendstock performance and reduce soot formation. However, it is little studied from both experimental and modeling aspects. This work created detailed oxidation mechanisms for the four butyl acetate isomers (normal-, sec-, tert-, and iso-butyl acetate) at temperatures varying from 650 to 2000 K and pressures up to 100 atm using the Reaction Mechanism Generator. About 60% of species in each model have thermochemical parameters from published data or in-house quantum calculations, including fuel molecules and intermediate combustion products. Kinetics of essential primary reactions, retro-ene and hydrogen atom abstraction by OH or HO2, governing the fuel oxidation pathways, were also calculated quantum-mechanically. Simulation of the developed mechanisms indicates that the majority of the fuel will decompose into acetic acid and relevant butenes at elevated temperatures, making their ignition behaviors similar to butenes. The adaptability of the developed models to high-temperature pyrolysis systems was tested against newly collected high-pressure shock experiments; the simulated CO mole fraction time histories have a reasonable agreement with the laser measurement in the shock tube. This work reveals the high-temperature oxidation chemistry of butyl acetates and demonstrates the validity of predictive models for biofuel chemistry established on accurate thermochemical and kinetic parameters.

Genomes-based MLST, cgMLST, wgMLST and SNP analysis of Salmonella Typhimurium from animals and humans.

Salmonella Typhimurium (S. Typhimurium) is an important food-borne and zoonotic pathogen that causes salmonellosis. With the development of whole genome sequencing (WGS), genome-based typing has been widely applied to bacteriology. In this study, we investigated genotyping and phylogenetic clusters of S. Typhimurium isolates from humans and animals in different provinces (including Beijing, Shandong, Guangxi, Shaanxi, Henan, and Shanghai) of China during 2009-2018 using multi locus sequence typing (MLST), core genome MLST (cgMLST), whole genome MLST (wgMLST) and single nucleotide polymorphism (SNP) based on WGS. 29 S. Typhimurium isolates from chicken (n = 22), sick pigeon (n = 2), patients (n = 4) and sick swine (n = 1) were tested. MLST analysis showed S. Typhimurium strains were divided into four STs, namely ST19 (n = 14), ST34 (n = 12), ST128 (n = 2) and ST1544 (n = 1). cgMLST and wgMLST divided 29 strains into 27 cgSTs and 29 wgST, respectively. Phylogenetic clustering showed that all isolates were divided into 4 clusters and 4 singletons. SNP analysis was used to examine MLST, cgMLST, wgMLST analysis. Finally, comparisons of MLST, cgMLST, wgMLST, and SNP were analyzed and the results showed their precision increased in order. In summary, genomic typing and phylogenetic relationships of 29 S. Typhimurium strains from different sources in China were analyzed. These findings were beneficial to investigate molecular pathogenesis, bacterial diversity, and traceability analysis of Salmonella.

Insights into the Genetic Determination of the Autotetraploid Potato Plant Height.

Plant height is an important characteristic, the modification of which can improve the ability of stress adaptation as well as the yield. In this study, genome-wide association analysis was performed for plant height traits in 370 potato cultivars using the tetraploid potato genome as a reference. A total of 92 significant single nucleotide polymorphism (SNP) loci for plant height were obtained, which were particularly significant in haplotypes A3 and A4 on chromosome 1 and A1, A2, and A4 on chromosome 5. Thirty-five candidate genes were identified that were mainly involved in the gibberellin and brassinolide signal transduction pathways, including the FAR1 gene, methyltransferase, ethylene response factor, and ubiquitin protein ligase. Among them, PIF3 and GID1a were only present on chromosome 1, with PIF3 in all four haplotypes and GID1a in haplotype A3. This could lead to more effective genetic loci for molecular marker-assisted selection breeding as well as more precise localization and cloning of genes for plant height traits in potatoes.

Synthesis, photoluminescence and electroluminescence properties of a new blue emitter with aggregation-induced emission and thermally activated delayed fluorescence characteristics.

The emitters with aggregation-induced emission (AIE) and thermally activated delayed fluorescence (TADF) characteristics are in high demand in organic light-emitting diodes (OLEDs) owing to their strong fluorescence and high exciton utilization under electrical excitation. Herein, a blue emitter, 10-(3-((3,5-di(9H-carbazol-9-yl)phenyl)sulfonyl)phenyl)-9,9-dimethyl-9,10-dihydroacridine (m-CZ-DPS-DMAC), was synthesized by incorporating carbazole as skeleton, acridine as electron donor, and diphenyl sulfone as electron acceptor. m-CZ-DPS-DMAC emits weak fluorescence in good solvent, while it is obviously enhanced in the aggregate state, which is typical of AIE molecules. Meanwhile, the energy levels of the singlet and triplet states (ΔEST) of the molecule is relatively small, and it also exhibits obvious temperature dependence and oxygen sensitivity, which directly proves its TADF properties. In view of the above properties, a series of non-doped and doped OLEDs were prepared using m-CZ-DPS-DMAC as light-emitting layers. Among them, non-doped OLED (device A) displays blue emission (488 nm) with the turn-on voltage (Von), the maximum luminance (Lmax), the maximum current efficiency (CEmax), the maximum power efficiency (PEmax) and the maximum external quantum efficiency (EQEmax) of 2.6 V, 3460 cd m-2, 26.09 cd A-1, 29.26 lm W-1 and 10.05%, respectively. Doped OLED (device C) constructed based on m-CZ-DPS-DMAC doped 30% in DPEPO shows the satisfactory performance with the maximum emission peak of 486 nm, the Von of 2.8 V, the Lmax of 4571 cd m-2, the CEmax of 21.37 cd A-1, the PEmax of 22.37 lm W-1, and the EQEmax of 9.44%, respectively. The outstanding performance of m-CZ-DPS-DMAC proves that it is a potential material for designing blue OLEDs with AIE-TADF properties.

RMG Database for Chemical Property Prediction.

The Reaction Mechanism Generator (RMG) database for chemical property prediction is presented. The RMG database consists of curated datasets and estimators for accurately predicting the parameters necessary for constructing a wide variety of chemical kinetic mechanisms. These datasets and estimators are mostly published and enable prediction of thermodynamics, kinetics, solvation effects, and transport properties. For thermochemistry prediction, the RMG database contains 45 libraries of thermochemical parameters with a combination of 4564 entries and a group additivity scheme with 9 types of corrections including radical, polycyclic, and surface absorption corrections with 1580 total curated groups and parameters for a graph convolutional neural network trained using transfer learning from a set of >130 000 DFT calculations to 10 000 high-quality values. Correction schemes for solvent-solute effects, important for thermochemistry in the liquid phase, are available. They include tabulated values for 195 pure solvents and 152 common solutes and a group additivity scheme for predicting the properties of arbitrary solutes. For kinetics estimation, the database contains 92 libraries of kinetic parameters containing a combined 21 000 reactions and contains rate rule schemes for 87 reaction classes trained on 8655 curated training reactions. Additional libraries and estimators are available for transport properties. All of this information is easily accessible through the graphical user interface at https://rmg.mit.edu. Bulk or on-the-fly use can be facilitated by interfacing directly with the RMG Python package which can be installed from Anaconda. The RMG database provides kineticists with easy access to estimates of the many parameters they need to model and analyze kinetic systems. This helps to speed up and facilitate kinetic analysis by enabling easy hypothesis testing on pathways, by providing parameters for model construction, and by providing checks on kinetic parameters from other sources.

Pangenomic analysis of Chinese gastric cancer.

Pangenomic study might improve the completeness of human reference genome (GRCh38) and promote precision medicine. Here, we use an automated pipeline of human pangenomic analysis to build gastric cancer pan-genome for 185 paired deep sequencing data (370 samples), and characterize the gene presence-absence variations (PAVs) at whole genome level. Genes ACOT1, GSTM1, SIGLEC14 and UGT2B17 are identified as highly absent genes in gastric cancer population. A set of genes from unaligned sequences with GRCh38 are predicted. We successfully locate one of predicted genes GC0643 on chromosome 9q34.2. Overexpression of GC0643 significantly inhibits cell growth, cell migration and invasion, cell cycle progression, and induces cell apoptosis in cancer cells. The tumor suppressor functions can be reversed by shGC0643 knockdown. The GC0643 is approved by NCBI database (GenBank: MW194843.1). Collectively, the robust pan-genome strategy provides a deeper understanding of the gene PAVs in the human cancer genome.

Long-read sequencing of 111 rice genomes reveals significantly larger pan-genomes.

The concept of pan-genome, which is the collection of all genomes from a population, has shown a great potential in genomics study, especially for crop sciences. The rice pan-genome constructed from the second-generation sequencing (SGS) data is about 270 Mb larger than Nipponbare, the rice reference genome (NipRG), but it is still disadvantaged by incompleteness and loss of genomic contexts. The third-generation sequencing (TGS) with long reads can help to construct better pan-genomes. In this paper, we report a high-quality rice pan-genome construction method by introducing a series of new steps to deal with the long-read data, including unmapped sequence block filtering, redundancy removing, and sequence block elongating. Compared to NipRG, the long-read sequencing-based pan-genome constructed from 105 rice accessions, which contains 604 Mb novel sequences, is much more comprehensive than the one constructed from ∼3000 rice genomes sequenced with short reads. The repetitive sequences are the main components of novel sequences, which partially explain the differences between the pan-genomes based on TGS and SGS. Adding six wild rice accessions, there are about 879 Mb novel sequences and 19,000 novel genes in the rice pan-genome in total. In addition, we have created high-quality reference genomes for all representative rice populations, including five gapless reference genomes. This study has made significant progress in our understanding of the rice pan-genome, and this pan-genome construction method for long-read data can be applied to accelerate a broad range of genomics studies.

Gene Presence/Absence Variation analysis of coronavirus family displays its pan-genomic diversity.

SARS-CoV-2 belongs to the coronavirus family. Comparing genomic features of viral genomes of coronavirus family can improve our understanding about SARS-CoV-2. Here we present the first pan-genome analysis of 3,932 whole genomes of 101 species out of 4 genera from the coronavirus family. We found that a total of 181 genes in the pan-genome of coronavirus family, among which only 3 genes, the S gene, M gene and N gene, are highly conserved. We also constructed a pan-genome from 23,539 whole genomes of SARS-CoV-2. There are 13 genes in total in the SARS-CoV-2 pan-genome. All of the 13 genes are core genes for SARS-CoV-2. The pan-genome of coronaviruses shows a lower level of diversity than the pan-genomes of other RNA viruses, which contain no core gene. The three highly conserved genes in coronavirus family, which are also core genes in SARS-CoV-2 pan-genome, could be potential targets in developing nucleic acid diagnostic reagents with a decreased possibility of cross-reaction with other coronavirus species.