The Genome Sequence Archive family (GSA family) provides a comprehensive suite of database resources for archiving, retrieving, and sharing multi-omics data for the global academic and industrial communities. It currently comprises four distinct database members: the Genome Sequence Archive (GSA, https://ngdc.cncb.ac.cn/gsa), the Genome Sequence Archive for Human (GSA-Human, https://ngdc.cncb.ac.cn/gsa-human), the Open Archive for Miscellaneous Data (OMIX, https://ngdc.cncb.ac.cn/omix), and the Open Biomedical Imaging Archive (OBIA, https://ngdc.cncb.ac.cn/obia). Compared to its 2021 version, the GSA family has expanded significantly by introducing a new repository, the OBIA, and by comprehensively upgrading the existing databases. Notable enhancements to the existing members include broadening the range of accepted data types, strengthening quality control systems, improving the data retrieval system, and refining data-sharing management mechanisms.

N6-methyladenosine (m6A) is an important epitranscriptomic mark with high abundance in the brain. Recently, it has been found to be involved in the regulation of memory formation and mammalian cortical neurogenesis. However, while it is now established that m6A methylation occurs in a spatially restricted manner, its functions in specific brain regions still await elucidation. We identify widespread and dynamic RNA m6A methylation in the developing mouse cerebellum and further uncover distinct features of continuous and temporal-specific m6A methylation across the four postnatal developmental processes. Temporal-specific m6A peaks from P7 to P60 exhibit remarkable changes in their distribution patterns along the mRNA transcripts. We also show spatiotemporal-specific expression of m6A writers METTL3, METTL14, and WTAP and erasers ALKBH5 and FTO in the mouse cerebellum. Ectopic expression of METTL3 mediated by lentivirus infection leads to disorganized structure of both Purkinje and glial cells. In addition, under hypobaric hypoxia exposure, Alkbh5-deletion causes abnormal cell proliferation and differentiation in the cerebellum through disturbing the balance of RNA m6A methylation in different cell fate determination genes. Notably, nuclear export of the hypermethylated RNAs is enhanced in the cerebellum of Alkbh5-deficient mice exposed to hypobaric hypoxia. Together, our findings provide strong evidence that RNA m6A methylation is controlled in a precise spatiotemporal manner and participates in the regulation of postnatal development of the mouse cerebellum.

GWAS Atlas (https://bigd.big.ac.cn/gwas/) is a manually curated resource of genome-wide variant-trait associations for a wide range of species. Unlike existing related resources, it features comprehensive integration of a high-quality collection of 75 467 variant-trait associations for 614 traits across 7 cultivated plants (cotton, Japanese apricot, maize, rapeseed, rice, sorghum and soybean) and two domesticated animals (goat and pig), which were manually curated from 254 publications. We integrated these associations into GWAS Atlas and presented them in terms of variants, genes, traits, studies and publications. More importantly, all associations and traits were annotated and organized based on a suite of ontologies (Plant Trait Ontology, Animal Trait Ontology for Livestock, etc.). Taken together, GWAS Atlas integrates high-quality curated GWAS associations for animals and plants and provides user-friendly web interfaces for data browsing and downloading, accordingly serving as a valuable resource for genetic research of important traits and breeding application.

N ⁶ -methyladenosine (m ⁶ A) is the most abundant epitranscriptomic mark found on mRNA and has important roles in various physiological processes. Despite the relatively high m ⁶ A levels in the brain, its potential functions in the brain remain largely unexplored. We performed a transcriptome-wide methylation analysis using the mouse brain to depict its region-specific methylation profile. RNA methylation levels in mouse cerebellum are generally higher than those in the cerebral cortex. Heterogeneity of RNA methylation exists across different brain regions and different types of neural cells including the mRNAs to be methylated, their methylation levels and methylation site selection. Common and region-specific methylation have different preferences for methylation site selection and thereby different impacts on their biological functions. In addition, high methylation levels of fragile X mental retardation protein (FMRP) target mRNAs suggest that m ⁶ A methylation is likely to be used for selective recognition of target mRNAs by FMRP in the synapse. Overall, we provide a region-specific map of RNA m ⁶ A methylation and characterize the distinct features of specific and common methylation in mouse cerebellum and cerebral cortex. Our results imply that RNA m ⁶ A methylation is a newly identified element in the region-specific gene regulatory network in the mouse brain.

Background: Housekeeping (HK) genes are ubiquitously expressed in all tissue/cell types and constitute a basal transcriptome for the maintenance of basic cellular functions. Partitioning transcriptomes into HK and tissue-specific (TS) genes relatively is fundamental for studying gene expression and cellular differentiation. Although many studies have aimed at large-scale and thorough categorization of human HK genes, a meaningful consensus has yet to be reached. Results: We collected two latest gene expression datasets (both EST and microarray data) from public databases and analyzed the gene expression profiles in 18 human tissues that have been well-documented by both two data types. Benchmarked by a manually-curated HK gene collection (HK408), we demonstrated that present data from EST sampling was far from saturated, and the inadequacy has limited the gene detectability and our understanding of TS expressions. Due to a likely over-stringent threshold, microarray data showed higher false negative rate compared with EST data, leading to a significant underestimation of HK genes. Based on EST data, we found that 40.0% of the currently annotated human genes were universally expressed in at least 16 of 18 tissues, as compared to only 5.1% specifically expressed in a single tissue. Our current EST-based estimate on human HK genes ranged from 3,140 to 6,909 in number, a ten-fold increase in comparison with previous microarray-based estimates. Conclusion: We concluded that a significant fraction of human genes, at least in the currently annotated data depositories, was broadly expressed. Our understanding of tissue-specific expression was still preliminary and required much more large-scale and high-quality transcriptomic data in future studies. The new HK gene list categorized in this study will be useful for genome-wide analyses on structural and functional features of HK genes.

Background: Gene expression is a key determinant of cellular response. Natural variation in gene expression bridges genetic variation to phenotypic alteration. Identification of the regulatory variants controlling the gene expression in response to drought, a major environmental threat of crop production worldwide, is of great value for drought-tolerant gene identification.Results: A total of 627 RNA-seq analyses are performed for 224 maize accessions which represent a wide genetic diversity under three water regimes; 73,573 eQTLs are detected for about 30,000 expressing genes with high-density genome-wide single nucleotide polymorphisms, reflecting a comprehensive and dynamic genetic architecture of gene expression in response to drought. The regulatory variants controlling the gene expression constitutively or drought-dynamically are unraveled. Focusing on dynamic regulatory variants resolved to genes encoding transcription factors, a drought-responsive network reflecting a hierarchy of transcription factors and their target genes is built. Moreover, 97 genes are prioritized to associate with drought tolerance due to their expression variations through the Mendelian randomization analysis. One of the candidate genes,Abscisic acid 8′-hydroxylase, is verified to play a negative role in plant drought tolerance.Conclusions: This study unravels the effects of genetic variants on gene expression dynamics in drought response which allows us to better understand the role of distal and proximal genetic effects on gene expression and phenotypic plasticity. The prioritized drought-associated genes may serve as direct targets for functional investigation or allelic mining.