Rujiao Li

Epigenome-wide association studies (EWAS) has become an indispensable approach for elucidating the epigenetic basis of complex traits. EWAS Open Platform (https://ngdc.cncb.ac.cn/ewas/) includes three main components: EWAS Atlas (curated associations from publications), EWAS Data Hub (normalized DNA methylation array data), and EWAS Toolkit (one-stop analysis services). Here, we present a new release of EWAS Open Platform with the following significant updates and enhancements: (i) Expanded information: EWAS Atlas houses over 800 000 associations and incorporates an additional 17 000 curated causal relationships. EWAS Data Hub contains >180 000 batch-corrected samples, which incorporate data from newly added Illumina MethylationEPIC v2.0 BeadChip (935K) as well as trait-specific methylation profiles. EWAS Toolkit now provides an online batch correction tool and an interactive epigenetic causal network. (ii) Enhanced interoperability: data, knowledge, and toolkit are fully interconnected through a unified retrieval, offering integrated summaries and visualization capabilities. (iii) Artificial intelligence (AI)-based service: the platform is newly equipped with an AI-assisted question-answering service, allowing users to interactively explore EWAS-related questions and generate tailored insights. Taken together, EWAS Open Platform has undergone a significant upgrade across data resources, analytical tools, and service functionalities, offering more advanced support for unraveling complex molecular mechanisms from an epigenomic perspective.

The ribosomal DNA (rDNA) constitutes a remarkably conserved DNA sequence within species, located in the area of the nucleolus, and responsible for coding three major types of rRNAs (18S, 5.8S and 28S). While historical investigations into rDNA focused on its structure and coding capabilities, recent research has turned to explore its functional roles in various biological processes. In this review, we summarize the main findings of rDNA methylation with embryonic development, aging and diseases in multiple species, including epigenetic alterations, related biological processes and potential applications of rDNA methylation. We present an overview of current related research and identify gaps in this field.

Perennial woody plants hold vital ecological significance, distinguished by their unique traits. While significant progress has been made in their genomic and functional studies, a major challenge persists: the absence of a comprehensive reference platform for collection, integration and in-depth analysis of the vast amount of data. Here, we present PPGR (Resource for Perennial Plant Genomes and Regulation; https://ngdc.cncb.ac.cn/ppgr/) to address this critical gap, by collecting, integrating, analyzing and visualizing genomic, gene regulation and functional data of perennial plants. PPGR currently includes 60 species, 847 million protein–protein/TF (transcription factor)-target interactions, 9016 transcriptome samples under various environmental conditions and genetic backgrounds. Noteworthy is the focus on genes that regulate wood production, seasonal dormancy, terpene biosynthesis and leaf senescence representing a wealth of information derived from experimental data, literature mining, public databases and genomic predictions. Furthermore, PPGR incorporates a range of multi-omics search and analysis tools to facilitate browsing and application of these extensive datasets. PPGR represents a comprehensive and high-quality resource for perennial plants, substantiated by an illustrative case study that demonstrates its capacity in unraveling gene functions and shedding light on potential regulatory processes.

DNA methylation, as the most intensively studied epigenetic mark, regulates gene expression in numerous biological processes including development, aging, and disease. With the rapid accumulation of whole-genome bisulfite sequencing data, integrating, archiving, analyzing, and visualizing those data becomes critical. Since its first publication in 2015, MethBank has been continuously updated to include more DNA methylomes across more diverse species. Here, we present MethBank 4.0 (https://ngdc.cncb.ac.cn/methbank/), which reports an increase of 309% in data volume, with 1449 single-base resolution methylomes of 23 species, covering 236 tissues/cell lines and 15 biological contexts. Value-added information, such as more rigorous quality evaluation, more standardized metadata, and comprehensive downstream annotations have been integrated in the new version. Moreover, expert-curated knowledge modules of featured differentially methylated genes associated with biological contexts and methylation analysis tools have been incorporated as new components of MethBank. In addition, MethBank 4.0 is equipped with a series of new web interfaces to browse, search, and visualize DNA methylation profiles and related information. With all these improvements, we believe the updated MethBank 4.0 will serve as a fundamental resource to provide a wide range of data services for the global research community.

Alternative splicing (AS) is a fundamental process that governs almost all aspects of cellular functions, and dysregulation in this process has been implicated in tumor initiation, progression and treatment resistance. With accumulating studies of carcinogenic mis-splicing in cancers, there is an urgent demand to integrate cancer-associated splicing changes to better understand their internal cross-talks and functional consequences from a global view. However, a resource of key functional AS events in human cancers is still lacking. To fill the gap, we developed ASCancer Atlas (https://ngdc.cncb.ac.cn/ascancer), a comprehensive knowledgebase of aberrant splicing in human cancers. Compared to extant databases, ASCancer Atlas features a high-confidence collection of 2006 cancer-associated splicing events experimentally proved to promote tumorigenesis, a systematic splicing regulatory network, and a suit of multi-scale online analysis tools. For each event, we manually curated the functional axis including upstream splicing regulators, splicing event annotations, downstream oncogenic effects, and possible therapeutic strategies. ASCancer Atlas also houses about 2 million computationally putative splicing events. Additionally, a user-friendly web interface was built to enable users to easily browse, search, visualize, analyze, and download all splicing events. Overall, ASCancer Atlas provides a unique resource to study the functional roles of splicing dysregulation in human cancers.

Single-cell transcriptome studies have revealed immune dysfunction in COVID-19 patients, including lymphopenia, T cell exhaustion, and increased levels of pro-inflammatory cytokines, while DNA methylation plays an important role in the regulation of immune response and inflammatory response. The specific cell types of immune responses regulated by DNA methylation in COVID-19 patients will be better understood by exploring the COVID-19 DNA methylation variation at the cell-type level. Here, we developed an analytical pipeline to explore single-cell DNA methylation variations in COVID-19 patients by transferring bulk-tissue-level knowledge to the single-cell level. We discovered that the methylation variations in the whole blood of COVID-19 patients showed significant cell-type specificity with remarkable enrichment in gamma-delta T cells and presented a phenomenon of hypermethylation and low expression. Furthermore, we identified five genes whose methylation variations were associated with several cell types. Among them, S100A9, AHNAK, and CX3CR1 have been reported as potential COVID-19 biomarkers previously, and the others (TRAF3IP3 and LFNG) are closely associated with the immune and virus-related signaling pathways. We propose that they might serve as potential epigenetic biomarkers for COVID-19 and could play roles in important biological processes such as the immune response and antiviral activity.

Epigenome-Wide Association Study (EWAS) has become a standard strategy to discover DNA methylation variation of different phenotypes. Since 2018, we have developed EWAS Atlas and EWAS Data Hub to integrate a growing volume of EWAS knowledge and data, respectively. Here, we present EWAS Open Platform (https://ngdc.cncb.ac.cn/ewas) that includes EWAS Atlas, EWAS Data Hub and the newly developed EWAS Toolkit. In the current implementation, EWAS Open Platform integrates 617 018 high-quality EWAS associations from 910 publications, covering 51 phenotypes, 275 diseases and 104 environmental factors. It also provides well-normalized DNA methylation array data and the corresponding metadata from 115 852 samples, which involve 707 tissues, 218 cell lines and 528 diseases. Taking advantage of integrated knowledge and data in EWAS Atlas and EWAS Data Hub, EWAS Open Platform equips with EWAS Toolkit, a powerful one-stop site for EWAS enrichment, annotation, and knowledge network construction and visualization. Collectively, EWAS Open Platform provides open access to EWAS knowledge, data and toolkit and thus bears great utility for a broader range of relevant research.

Single-cell bisulfite sequencing methods are widely used to assess epigenomic heterogeneity in cell states. Over the past few years, large amounts of data have been generated and facilitated deeper understanding of the epigenetic regulation of many key biological processes including early embryonic development, cell differentiation and tumor progression. It is an urgent need to build a functional resource platform with the massive amount of data. Here, we present scMethBank, the first open access and comprehensive database dedicated to the collection, integration, analysis and visualization of single-cell DNA methylation data and metadata. Current release of scMethBank includes processed single-cell bisulfite sequencing data and curated metadata of 8328 samples derived from 15 public single-cell datasets, involving two species (human and mouse), 29 cell types and two diseases. In summary, scMethBank aims to assist researchers who are interested in cell heterogeneity to explore and utilize whole genome methylation data at single-cell level by providing browse, search, visualization, download functions and user-friendly online tools. The database is accessible at: https://ngdc.cncb.ac.cn/methbank/scm/.

On January 22, 2020, China National Center for Bioinformation (CNCB) released the 2019 Novel Coronavirus Resource (2019nCoVR), an open-access information resource for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). 2019nCoVR features a comprehensive integration of sequence and clinical information for all publicly available SARS-CoV-2 isolates, which are manually curated with value-added annotations and quality evaluated by an automated in-house pipeline. Of particular note, 2019nCoVR offers systematic analyses to generate a dynamic landscape of SARS-CoV-2 genomic variations at a global scale. It provides all identified variants and their detailed statistics for each virus isolate, and congregates the quality score, functional annotation, and population frequency for each variant. Spatiotemporal change for each variant can be visualized and historical viral haplotype network maps for the course of the outbreak are also generated based on all complete and high-quality genomes available. Moreover, 2019nCoVR provides a full collection of SARS-CoV-2 relevant literature on the coronavirus disease 2019 (COVID-19), including published papers from PubMed as well as preprints from services such as bioRxiv and medRxiv through Europe PMC. Furthermore, by linking with relevant databases in CNCB, 2019nCoVR offers data submission services for raw sequence reads and assembled genomes, and data sharing with NCBI. Collectively, SARS-CoV-2 is updated daily to collect the latest information on genome sequences, variants, haplotypes, and literature for a timely reflection, making 2019nCoVR a valuable resource for the global research community. 2019nCoVR is accessible at https://bigd.big.ac.cn/ncov/.