Plant genomic resources at National Genomics Data Center: assisting in data-driven breeding applications.

Genomic data serve as an invaluable resource for unraveling the intricacies of the higher plant systems, including the constituent elements within and among species. Through various efforts in genomic data archiving, integrative analysis and value-added curation, the National Genomics Data Center (NGDC), which is a part of the China National Center for Bioinformation (CNCB), has successfully established and currently maintains a vast amount of database resources. This dedicated initiative of the NGDC facilitates a data-rich ecosystem that greatly strengthens and supports genomic research efforts. Here, we present a comprehensive overview of central repositories dedicated to archiving, presenting, and sharing plant omics data, introduce knowledgebases focused on variants or gene-based functional insights, highlight species-specific multiple omics database resources, and briefly review the online application tools. We intend that this review can be used as a guide map for plant researchers wishing to select effective data resources from the NGDC for their specific areas of study. Supplementary Information: The online version contains supplementary material available at 10.1007/s42994-023-00134-4.

Functional Characterization of CsSWEET5a, a Cucumber Hexose Transporter That Mediates the Hexose Supply for Pollen Development and Rescues Male Fertility in Arabidopsis.

Pollen cells require large amounts of sugars from the anther to support their development, which is critical for plant sexual reproduction and crop yield. Sugars Will Eventually be Exported Transporters (SWEETs) have been shown to play an important role in the apoplasmic unloading of sugars from anther tissues into symplasmically isolated developing pollen cells and thereby affect the sugar supply for pollen development. However, among the 17 CsSWEET genes identified in the cucumber (Cucumis sativus L.) genome, the CsSWEET gene involved in this process has not been identified. Here, a member of the SWEET gene family, CsSWEET5a, was identified and characterized. The quantitative real-time PCR and ß-glucuronidase expression analysis revealed that CsSWEET5a is highly expressed in the anthers and pollen cells of male cucumber flowers from the microsporocyte stage (stage 9) to the mature pollen stage (stage 12). Its subcellular localization indicated that the CsSWEET5a protein is localized to the plasma membrane. The heterologous expression assays in yeast demonstrated that CsSWEET5a encodes a hexose transporter that can complement both glucose and fructose transport deficiencies. CsSWEET5a can significantly rescue the pollen viability and fertility of atsweet8 mutant Arabidopsis plants. The possible role of CsSWEET5a in supplying hexose to developing pollen cells via the apoplast is also discussed.

BioKA: a curated and integrated biomarker knowledgebase for animals.

Biomarkers play an important role in various area such as personalized medicine, drug development, clinical care, and molecule breeding. However, existing animals' biomarker resources predominantly focus on human diseases, leaving a significant gap in non-human animal disease understanding and breeding research. To address this limitation, we present BioKA (Biomarker Knowledgebase for Animals, https://ngdc.cncb.ac.cn/bioka), a curated and integrated knowledgebase encompassing multiple animal species, diseases/traits, and annotated resources. Currently, BioKA houses 16 296 biomarkers associated with 951 mapped diseases/traits across 31 species from 4747 references, including 11 925 gene/protein biomarkers, 1784 miRNA biomarkers, 1043 mutation biomarkers, 773 metabolic biomarkers, 357 circRNA biomarkers and 127 lncRNA biomarkers. Furthermore, BioKA integrates various annotations such as GOs, protein structures, protein-protein interaction networks, miRNA targets and so on, and constructs an interactive knowledge network of biomarkers including circRNA-miRNA-mRNA associations, lncRNA-miRNA associations and protein-protein associations, which is convenient for efficient data exploration. Moreover, BioKA provides detailed information on 308 breeds/strains of 13 species, and homologous annotations for 8784 biomarkers across 16 species, and offers three online application tools. The comprehensive knowledge provided by BioKA not only advances human disease research but also contributes to a deeper understanding of animal diseases and supports livestock breeding.

OPIA: an open archive of plant images and related phenotypic traits.

High-throughput plant phenotype acquisition technologies have been extensively utilized in plant phenomics studies, leading to vast quantities of images and image-based phenotypic traits (i-traits) that are critically essential for accelerating germplasm screening, plant diseases identification and biotic & abiotic stress classification. Here, we present the Open Plant Image Archive (OPIA, https://ngdc.cncb.ac.cn/opia/), an open archive of plant images and i-traits derived from high-throughput phenotyping platforms. Currently, OPIA houses 56 datasets across 11 plants, comprising a total of 566 225 images with 2 417 186 labeled instances. Notably, it incorporates 56 i-traits of 93 rice and 105 wheat cultivars based on 18 644 individual RGB images, and these i-traits are further annotated based on the Plant Phenotype and Trait Ontology (PPTO) and cross-linked with GWAS Atlas. Additionally, each dataset in OPIA is assigned an evaluation score that takes account of image data volume, image resolution, and the number of labeled instances. More importantly, OPIA is equipped with useful tools for online image pre-processing and intelligent prediction. Collectively, OPIA provides open access to valuable datasets, pre-trained models, and phenotypic traits across diverse plants and thus bears great potential to play a crucial role in facilitating artificial intelligence-assisted breeding research.

Progress in oncolytic viruses modified with nanomaterials for intravenous application.

In oncolytic virus (OV) therapy, a critical component of tumor immunotherapy, viruses selectively infect, replicate within, and eventually destroy tumor cells. Simultaneously, this therapy activates immune responses and mobilizes immune cells, thereby eliminating residual or distant cancer cells. However, because of OVs' high immunogenicity and immune clearance during circulation, their clinical applications are currently limited to intratumoral injections, and their use is severely restricted. In recent years, numerous studies have used nanomaterials to modify OVs to decrease virulence and increase safety for intravenous injection. The most commonly used nanomaterials for modifying OVs are liposomes, polymers, and albumin, because of their biosafety, practicability, and effectiveness. The aim of this review is to summarize progress in the use of these nanomaterials in preclinical experiments to modify OVs and to discuss the challenges encountered from basic research to clinical application.

RCoV19: A One-stop Hub for SARS-CoV-2 Genome Data Integration, Variant Monitoring, and Risk Pre-warning.

The Resource for Coronavirus 2019 (RCoV19) is an open-access information resource dedicated to providing valuable data on the genomes, mutations, and variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this updated implementation of RCoV19, we have made significant improvements and advancements over the previous version. Firstly, we have implemented a highly refined genome data curation model. This model now features an automated integration pipeline and optimized curation rules, enabling efficient daily updates of data in RCoV19. Secondly, we have developed a global and regional lineage evolution monitoring platform, alongside an outbreak risk pre-warning system. These additions provide a comprehensive understanding of SARS-CoV-2 evolution and transmission patterns, enabling better preparedness and response strategies. Thirdly, we have developed a powerful interactive mutation spectrum comparison module. This module allows users to compare and analyze mutation patterns, assisting in the detection of potential new lineages. Furthermore, we have incorporated a comprehensive knowledgebase on mutation effects. This knowledgebase serves as a valuable resource for retrieving information on the functional implications of specific mutations. In summary, RCoV19 serves as a vital scientific resource, providing access to valuable data, relevant information, and technical support in the global fight against COVID-19. The complete contents of RCoV19 are available to the public at https://ngdc.cncb.ac.cn/ncov/.

The Triaging Effect of the Human Papillomavirus 16/18 E7 Oncoprotein Assay in HPV 16/18-Positive Patients for High-Grade Cervical Intraepithelial Neoplasia Screening: A Cross-Sectional Study.

Objective: To investigate the triaging efficacy of the human papillomavirus (HPV) 16/18 E7 oncoprotein assay for high-grade cervical intraepithelial neoplasia (CIN2+) screening in HPV 16/18-positive patients in a tertiary hospital in China. Methods: We collected 476 cervical cell samples from women who tested positive for HPV 16/18 in the gynecological clinic of Peking Union Medical College Hospital between September 2018 and September 2022 and analyzed them by the HPV 16/18 E7 oncoprotein assay before colposcopy and biopsy. The study assessed the triaging efficacy of the HPV 16/18 E7 oncoprotein assay in HPV 16/18-positive patients by analyzing its performance against the gold standard of histologically confirmed CIN2+. Results: The positive rate of the HPV 16/18 E7 oncoprotein assay was 41.0% (114/278) in the negative for intraepithelial lesions and malignancy/CIN1 group and 80.3% (159/198) in the CIN2+ group. For triage of women with a positive HPV 16/18 test for CIN2+ detection, the HPV 16/18 E7 oncoprotein assay had a sensitivity, specificity, positive predictive value, and negative predictive value of 80.3%, 59.4%, 58.5%, and 80.9%, respectively. Furthermore, longitudinal follow-up of five patients showed a good correlation between the expression of the HPV 16/18 E7 oncoprotein and cervical lesion grades. Conclusions: As a triage method for HPV 16/18-positive patients, the HPV 16/18 E7 oncoprotein assay improves the specificity, reduces the colposcopy referral rate, and has the potential for long-term monitoring of high-grade CIN.

McAN: a novel computational algorithm and platform for constructing and visualizing haplotype networks.

Haplotype networks are graphs used to represent evolutionary relationships between a set of taxa and are characterized by intuitiveness in analyzing genealogical relationships of closely related genomes. We here propose a novel algorithm termed McAN that considers mutation spectrum history (mutations in ancestry haplotype should be contained in descendant haplotype), node size (corresponding to sample count for a given node) and sampling time when constructing haplotype network. We show that McAN is two orders of magnitude faster than state-of-the-art algorithms without losing accuracy, making it suitable for analysis of a large number of sequences. Based on our algorithm, we developed an online web server and offline tool for haplotype network construction, community lineage determination, and interactive network visualization. We demonstrate that McAN is highly suitable for analyzing and visualizing massive genomic data and is helpful to enhance the understanding of genome evolution. Availability: Source code is written in C/C++ and available at https://github.com/Theory-Lun/McAN and https://ngdc.cncb.ac.cn/biocode/tools/BT007301 under the MIT license. Web server is available at https://ngdc.cncb.ac.cn/bit/hapnet/. SARS-CoV-2 dataset are available at https://ngdc.cncb.ac.cn/ncov/. Contact: songshh@big.ac.cn (Song S), zhaowm@big.ac.cn (Zhao W), baoym@big.ac.cn (Bao Y), zhangzhang@big.ac.cn (Zhang Z), ybxue@big.ac.cn (Xue Y).

Comparative Transcriptome and Metabolome Analyses of Broccoli Germplasms with Purple and Green Curds Reveal the Structural Genes and Transitional Regulators Regulating Color Formation.

Owing to the high anthocyanin content, broccoli varieties with purple curds have become more popular in food inventories, while the genetic mechanisms of anthocyanin biosynthesis pathways remain largely unknown. We bred a pair of near-isogenic lines (NILs), GB767 and PB767, whose curds exhibited green and purple colors, respectively, due to the purple sepals of florets. RNA sequencing and widely targeted metabolic analyses were conducted. Compared with GB767, eighteen anthocyanin biosynthesis-related genes exhibited significantly higher expressions in PB767, and in turn, the expression level of BolMYBL2.1 was attenuated. A comparison of the metabolites in the flavonoid biosynthetic pathways revealed 142 differentially accumulated metabolites, among which higher content of anthocyanins was responsible for the purple color of PB767. Interestingly, the total cyanidin contents were similar between the curds of NILs, whereas total delphinidin contents were increased by more than 170 times in purple curds, presumably due to a non-canonical F3'H/CYP75B gene, BolC02g015480.2J, with elevated expression in PB767. Furthermore, correlation analysis further confirmed that the identified nineteen DEGs were significantly correlated with seven differentially accumulated anthocyanins in PB767. Together, these results identified the metabolic factors and genes that contribute to the purplish curds, which could lay foundations for the breeding programs of purple broccoli.

Preparation and characterization of functionalized chitosan/polyvinyl alcohol composite films incorporated with cinnamon essential oil as an active packaging material.

In this study, amphiphilic chitosan (NPCS-CA) was synthesized by grafting quaternary phosphonium salt and cholic acid onto the chain of chitosan, aiming to develop an active edible film based on NPCS-CA and polyvinyl alcohol (PVA) incorporated with cinnamon essential oil (CEO) by the casting method. The chemical structure of the chitosan derivative was characterized by FT-IR, 1H NMR and XRD. Through the characterization of FT-IR, TGA, mechanical and barrier properties of the composite films, the optimal proportion of NPCS-CA/PVA was determined as 5/5. And, the tensile strength and elongation at break of the NPCS-CA/PVA (5/5) film with 0.4 % CEO were 20.32 MPa and 65.73 %, respectively. The results revealed that the NPCS-CA/PVA-CEO composite films exhibited an excellent ultraviolet barrier property at 200-300 nm and significantly reduced oxygen permeability, carbon dioxide permeability and water vapor permeability. Furthermore, the antibacterial property of film-forming solutions against E. coli, S. aureus, and C. lagenarium was distinctly improved with the increase of NPCS-CA/PVA proportion. And, the multifunctional films effectively extended the shelf-life of mangoes at 25 °C based on the characterization of surface changes and quality indexes. The NPCS-CA/PVA-CEO films could be developed as biocomposite food packaging material.

Nutrient controlled release performance of bio-based coated fertilizer enhanced by synergistic effects of liquefied starch and siloxane.

The porous structure and hydrophilicity of coating shells affect the nutrient controlled-release performance of castor oil-based (CO) coated fertilizers. In order to solve these problems, in this study, the castor oil-based polyurethane (PCU) coating material was modified with liquefied starch polyol (LS) and siloxane, and a new coating material with cross-linked network structure and hydrophobic surface was synthesized, and used it to prepare the coated controlled-release urea (SSPCU). The results demonstrated that the cross-linked network formed by LS and CO improved the density and reduced the pores on the surface of the coating shells. The siloxane was grafted on the surface of coating shells to improve its hydrophobicity and thus delayed water entry. The nitrogen release experiment indicated that the synergistic effects of LS and siloxane improved the nitrogen controlled-release performance of bio-based coated fertilizers. Nutrient released longevity of SSPCU with 7 % coating percentage reached >63 days. Moreover, the nutrient release mechanism of coated fertilizer was further revealed by the analysis of the release kinetics analysis. Therefore, the results of this study provide a new idea and technical support for development of efficient and environment-friendly bio-based coated controlled-release fertilizers.

HGD: an integrated homologous gene database across multiple species.

Homology is fundamental to infer genes' evolutionary processes and relationships with shared ancestry. Existing homolog gene resources vary in terms of inferring methods, homologous relationship and identifiers, posing inevitable difficulties for choosing and mapping homology results from one to another. Here, we present HGD (Homologous Gene Database, https://ngdc.cncb.ac.cn/hgd), a comprehensive homologs resource integrating multi-species, multi-resources and multi-omics, as a complement to existing resources providing public and one-stop data service. Currently, HGD houses a total of 112 383 644 homologous pairs for 37 species, including 19 animals, 16 plants and 2 microorganisms. Meanwhile, HGD integrates various annotations from public resources, including 16 909 homologs with traits, 276 670 homologs with variants, 398 573 homologs with expression and 536 852 homologs with gene ontology (GO) annotations. HGD provides a wide range of omics gene function annotations to help users gain a deeper understanding of gene function.

Amphiphilic chitosan/carboxymethyl gellan gum composite films enriched with mustard essential oil for mango preservation.

In this paper, amphiphilic chitosan and carboxymethyl modified gellan gum were synthesized to develop an active edible fresh-keeping material. The optimal weight ratio of CMCS-g-CA/CMGG was determined as 5:2 through the characterization of Fourier transform infrared (FT-IR), Thermogravimetric analysis (TGA), mechanical and barrier properties of the composite films. In addition, the water vapor permeability and oxygen permeability of CMCS-g-CA/CMGG composite films incorporated with mustard essential oil were all declined, and the antibacterial property of the composite film solutions against E. coli, S. aureus and Bacillus anthracis was distinctly improved with the increase of mustard essential oil (MEO) dosage. Furthermore, the CMCS-g-CA/CMGG + 2.0 µL/mL MEO composite film exhibited an effective preservation on mango fruits during 20 days of storage based on the characterization of surface appearance and quality indexes of fruits. Hence, the multifunctional CMCA-g-CA/CMGG/MEO composite films can be served as a prospective eco-friendly packaging material for fruit preservation.

Dual-grafted dextran based nanomicelles: Higher antioxidant, anti-inflammatory and cellular uptake efficiency for quercetin.

Quercetin (QCT) has antioxidant, anti-inflammatory, anti-tumor and other important pharmacological activities, but the poor water solubility limits its application. In this work, the amphiphilic dextran (ADEX) was prepared by grafting L-cysteine and octadecylamine onto carboxymethyl dextran with the grafting rate of 21.29 % and 19.35 %. Then, the QCT-loaded nanomicelles (QNMs) were prepared by using ADEX as wall material and the QCT as core material via ultrasonic self-assembly method. The particle size and zeta potential of QNMs were 372 nm and 31.4 mV. Under simulated gastric and simulated intestinal fluids, the cumulative release QNMs were 37.54 % and 52.13 % within 180 min, and the QNMs showed better stability in simulated gastric fluid. The QNMs showed significantly better PTIO, OH and O2- scavenging activities than QCT. In addition, QNMs could effectively down-regulate the expression of pro-inflammatory cytokines and promoted the expression of anti-inflammatory cytokine. The cellular uptake results proved that the QNMs were more easily absorbed by cells than free QCT, indicating that the nano-encapsulation procedure effectively improved the uptake efficiency of QCT by cells.

GWAS Atlas: an updated knowledgebase integrating more curated associations in plants and animals.

GWAS Atlas (https://ngdc.cncb.ac.cn/gwas/) is a manually curated resource of genome-wide genotype-to-phenotype associations for a wide range of species. Here, we present an updated implementation of GWAS Atlas by curating and incorporating more high-quality associations, with significant improvements and advances over the previous version. Specifically, the current release of GWAS Atlas incorporates a total of 278,109 curated genotype-to-phenotype associations for 1,444 different traits across 15 species (10 plants and 5 animals) from 830 publications and 3,432 studies. A collection of 6,084 lead SNPs of 439 traits and 486 experiment-validated causal variants of 157 traits are newly added. Moreover, 1,056 trait ontology terms are newly defined, resulting in 1,172 and 431 terms for Plant Phenotype and Trait Ontology and Animal Phenotype and Trait Ontology, respectively. Additionally, it is equipped with four online analysis tools and a submission platform, allowing users to perform data analysis and data submission. Collectively, as a core resource in the National Genomics Data Center, GWAS Atlas provides valuable genotype-to-phenotype associations for a diversity of species and thus plays an important role in agronomic trait study and molecular breeding.

Accurate identification of taxon-specific molecular markers in plants based on DNA signature sequence.

Accurate identification of plants remains a significant challenge for taxonomists and is the basis for plant diversity conservation. Although DNA barcoding methods are commonly used for plant identification, these are limited by the low amplification success and low discriminative power of selected genomic regions. In this study, we developed a k-mer-based approach, the DNA signature sequence (DSS), to accurately identify plant taxon-specific markers, especially at the species level. DSS is a constant-length nucleotide sequence capable of identifying a taxon and distinguishing it from other taxa. In this study, we performed the first large-scale study of DSS markers in plants. DSS candidates of 3899 angiosperm plant species were calculated based on a chloroplast data set with 4356 assemblies. Using Sanger sequencing of PCR amplicons and high-throughput sequencing, DSSs were validated in four and 165 species, respectively. Based on this, the universality of the DSSs was over 79.38%. Several indicators influencing DSS marker identification and detection have also been evaluated, and common criteria for DSS application in plant identification have been proposed.

Synergistic antibacterial activity of chitosan modified by double antibacterial agents as coating material for fruits preservation.

Chitosan (CS) is a natural marine polysaccharide with good biocompatibility and biodegradability. But its poor water solubility and antibacterial activity limit its application in fruits preservation. In this study, based on the advantage of quaternary phosphonium salt (QP) and salicylic acid (SA) with good antibacterial activities and different antibacterial mechanisms, a novel antibacterial coating material was synthesized by grafting QP and SA onto CS. With the grafting of SA and QP onto CS, not only the crystallinity of CS molecules decreased and the water solubility improved, but also the antibacterial activity of CS-QP-SA against Escherichia coli and Staphylococcus aureus, and Colletotrichum gloeosporioides (anthracnose) improved by the synergistic effect of QP and SA. After 20 days storage, the mango fruits treated by CS-QP-SA had a weight loss rate of 12.86 %, the fruit decay incidence was 52.00 ± 1.70 %. Hence, the CS-QP-SA films effectively extending the storage time of mango fruits to a certain extent. The results of this study indicated that CS-QP-SA might be a promising preservative for fruits and vegetables.

METTL3 regulates m6A methylation of PTCH1 and GLI2 in Sonic hedgehog signaling to promote tumor progression in SHH-medulloblastoma.

SHH subgroup medulloblastoma (SHH-MB) is one of the most common malignant pediatric tumors that arises in the cerebellum. Previously, we showed that RNA m6A methylation participates in regulation of cerebellar development. Here we investigate whether dysregulated m6A methylation contributes to tumorigenesis of SHH-MB. We show that high expression of m6A methyltransferase METTL3 associates with worse survival in the patients with SHH-MB. A large number of hypermethylated transcripts are identified in SHH-MB tumor cells by m6A-seq. We find that METTL3 promotes tumor progression via activating Sonic hedgehog signaling. Mechanistically, METTL3 methylates PTCH1 and GLI2 RNAs and further regulates their RNA stability and translation. Importantly, targeting METTL3 by depleting METTL3 expression or treatment with its catalytic inhibitor STM2457 restrains tumor progression. Collectively, this study shows a critical function for METTL3 and m6A methylation in SHH-MB, indicative of a potential role of METTL3 as therapeutic target in SHH-MB.