bluuebunny/crossref_metadata_2025_split huggingface dataset:
3D-Spatiotemporal forecasting the expansion of supernova shells using deep learning towards high-resolution galaxy simulations
Authors: Hirashima Keiya , Moriwaki Kana , Fujii Michiko S , Hirai Yutaka , Saitoh Takayuki R , Makino Junichiro 
Published: October 2023

ABSTRACT
Supernova (SN) plays an important role in galaxy formation and evolution. In high-resolution galaxy simulations using massively parallel computing, short integration time-steps for SNe are serious bottlenecks. This is an urgent issue that needs to be resolved for future higher-resolution galaxy simulations. One possible solution would be to use the Hamiltonian splitting method, in which regions requiring short time-steps are integrated separately from the entire system. To apply this method to the particles affected by SNe in a smoothed particle hydrodynamics simulation, we need to detect the shape of the shell on and within which such SN-affected particles reside during the subsequent global step in advance. In this paper, we develop a deep learning model, 3D-Memory In Memory (3D-MIM), to predict a shell expansion after a SN explosion. Trained on turbulent cloud simulations with particle mass mgas = 1 M⊙, the model accurately reproduces the anisotropic shell shape, where densities decrease by over 10 per cent by the explosion. We also demonstrate that the model properly predicts the shell radius in the uniform medium beyond the training data set of inhomogeneous turbulent clouds. We conclude that our model enables the forecast of the shell and its interior where SN-affected particles will be present.
A high-resolution haplotype-resolved Reference panel constructed from the China Kadoorie Biobank Study
Authors: Yu Canqing , Lan Xianmei , Tao Ye , Guo Yu , Sun Dianjianyi , Qian Puyi , Zhou Yuwen , Walters Robin G , Li Linxuan , Zhu Yunqing , Zeng Jingyu , Millwood Iona Y , Guo Ruidong , Pei Pei , Yang Tao , Du Huaidong , Yang Fan , Yang Ling , Ren Fangyi , Chen Yiping , Chen Fengzhen , Jiang Xiaosen , Ye Zhiqiang , Dai Lanlan , Wei Xiaofeng , Xu Xun , Yang Huanming , Wang Jian , Chen Zhengming , Zhu Huanhuan , Lv Jun , Jin Xin , Li Liming 
Published: October 2023

Abstract
Precision medicine depends on high-accuracy individual-level genotype data. However, the whole-genome sequencing (WGS) is still not suitable for gigantic studies due to budget constraints. It is particularly important to construct highly accurate haplotype reference panel for genotype imputation. In this study, we used 10 000 samples with medium-depth WGS to construct a reference panel that we named the CKB reference panel. By imputing microarray datasets, it showed that the CKB panel outperformed compared panels in terms of both the number of well-imputed variants and imputation accuracy. In addition, we have completed the imputation of 100 706 microarrays with the CKB panel, and the after-imputed data is the hitherto largest whole genome data of the Chinese population. Furthermore, in the GWAS analysis of real phenotype height, the number of tested SNPs tripled and the number of significant SNPs doubled after imputation. Finally, we developed an online server for offering free genotype imputation service based on the CKB reference panel (https://db.cngb.org/imputation/). We believe that the CKB panel is of great value for imputing microarray or low-coverage genotype data of Chinese population, and potentially mixed populations. The imputation-completed 100 706 microarray data are enormous and precious resources of population genetic studies for complex traits and diseases.
Structural and functional basis of inositol hexaphosphate stimulation of NHEJ through stabilization of Ku-XLF interaction
Authors: Kefala Stavridi Antonia , Gontier Amandine , Morin Vincent , Frit Philippe , Ropars Virginie , Barboule Nadia , Racca Carine , Jonchhe Sagun , Morten Michael J , Andreani Jessica , Rak Alexey , Legrand Pierre , Bourand-Plantefol Alexa , Hardwick Steven W , Chirgadze Dimitri Y , Davey Paul , De Oliveira Taiana Maia , Rothenberg Eli , Britton Sebastien , Calsou Patrick , Blundell Tom L , Varela Paloma F , Chaplin Amanda K , Charbonnier Jean-Baptiste 
Published: October 2023

Abstract
The classical Non-Homologous End Joining (c-NHEJ) pathway is the predominant process in mammals for repairing endogenous, accidental or programmed DNA Double-Strand Breaks. c-NHEJ is regulated by several accessory factors, post-translational modifications, endogenous chemical agents and metabolites. The metabolite inositol-hexaphosphate (IP6) stimulates c-NHEJ by interacting with the Ku70–Ku80 heterodimer (Ku). We report cryo-EM structures of apo- and DNA-bound Ku in complex with IP6, at 3.5 Å and 2.74 Å resolutions respectively, and an X-ray crystallography structure of a Ku in complex with DNA and IP6 at 3.7 Å. The Ku-IP6 interaction is mediated predominantly via salt bridges at the interface of the Ku70 and Ku80 subunits. This interaction is distant from the DNA, DNA-PKcs, APLF and PAXX binding sites and in close proximity to XLF binding site. Biophysical experiments show that IP6 binding increases the thermal stability of Ku by 2°C in a DNA-dependent manner, stabilizes Ku on DNA and enhances XLF affinity for Ku. In cells, selected mutagenesis of the IP6 binding pocket reduces both Ku accrual at damaged sites and XLF enrolment in the NHEJ complex, which translate into a lower end-joining efficiency. Thus, this study defines the molecular bases of the IP6 metabolite stimulatory effect on the c-NHEJ repair activity.
HALL: a comprehensive database for human aging and longevity studies
Authors: Li Hao , Wu Song , Li Jiaming , Xiong Zhuang , Yang Kuan , Ye Weidong , Ren Jie , Wang Qiaoran , Xiong Muzhao , Zheng Zikai , Zhang Shuo , Han Zichu , Yang Peng , Jiang Beier , Ping Jiale , Zuo Yuesheng , Lu Xiaoyong , Zhai Qiaocheng , Yan Haoteng , Wang Si , Ma Shuai , Zhang Bing , Ye Jinlin , Qu Jing , Yang Yun-Gui , Zhang Feng , Liu Guang-Hui , Bao Yiming , Zhang Weiqi 
Published: October 2023

Abstract
Diverse individuals age at different rates and display variable susceptibilities to tissue aging, functional decline and aging-related diseases. Centenarians, exemplifying extreme longevity, serve as models for healthy aging. The field of human aging and longevity research is rapidly advancing, garnering significant attention and accumulating substantial data in recent years. Omics technologies, encompassing phenomics, genomics, transcriptomics, proteomics, metabolomics and microbiomics, have provided multidimensional insights and revolutionized cohort-based investigations into human aging and longevity. Accumulated data, covering diverse cells, tissues and cohorts across the lifespan necessitates the establishment of an open and integrated database. Addressing this, we established the Human Aging and Longevity Landscape (HALL), a comprehensive multi-omics repository encompassing a diverse spectrum of human cohorts, spanning from young adults to centenarians. The core objective of HALL is to foster healthy aging by offering an extensive repository of information on biomarkers that gauge the trajectory of human aging. Moreover, the database facilitates the development of diagnostic tools for aging-related conditions and empowers targeted interventions to enhance longevity. HALL is publicly available at https://ngdc.cncb.ac.cn/hall/index.
M2OR: a database of olfactory receptor–odorant pairs for understanding the molecular mechanisms of olfaction
Authors: Lalis Maxence , Hladiš Matej , Khalil Samar Abi , Briand Loïc , Fiorucci Sébastien , Topin Jérémie 
Published: October 2023

Abstract
Mammalian sense of smell is triggered by interaction between odorant molecules and a class of proteins, called olfactory receptors (ORs). These receptors, expressed at the surface of olfactory sensory neurons, encode myriad of distinct odors via a sophisticated activation pattern. However, determining the molecular recognition spectrum of ORs remains a major challenge. The Molecule to Olfactory Receptor database (M2OR, https://m2or.chemsensim.fr/) provides curated data that allows an easy exploration of the current state of the research on OR-molecule interaction. We have gathered a database of 75,050 bioassay experiments for 51 395 distinct OR-molecule pairs. Drawn from published literature and public databases, M2OR contains information about OR responses to molecules and their mixtures, receptor sequences and experimental details. Users can obtain information on the activity of a chosen molecule or a group of molecules, or search for agonists for a specific OR or a group of ORs. Advanced search allows for fine-grained queries using various metadata such as species or experimental assay system, and the database can be queried by multiple inputs via a batch search. Finally, for a given search query, users can access and download a curated aggregation of the experimental data into a binarized combinatorial code of olfaction.
Shortcut barcoding and early pooling for scalable multiplex single-cell reduced-representation CpG methylation sequencing at single nucleotide resolution
Authors: Mai Liyao , Wen Zebin , Zhang Yulong , Gao Yu , Lin Guanchuan , Lian Zhiwei , Yang Xiang , Zhou Jingjing , Lin Xianwei , Luo Chaochao , Peng Wanwan , Chen Caiming , Peng Jiajia , Liu Duolian , Marjani Sadie L , Tao Qian , Cui Yongping , Zhang Junxiao , Wu Xuedong , Weissman Sherman M , Pan Xinghua 
Published: October 2023

Abstract
DNA methylation is essential for a wide variety of biological processes, yet the development of a highly efficient and robust technology remains a challenge for routine single-cell analysis. We developed a multiplex scalable single-cell reduced representation bisulfite sequencing (msRRBS) technology. It allows cell-specific barcoded DNA fragments of individual cells to be pooled before bisulfite conversion, free of enzymatic modification or physical capture of the DNA ends, and achieves read mapping rates of 62.5 ± 3.9%, covering 60.0 ± 1.4% of CpG islands and 71.6 ± 1.6% of promoters in K562 cells. Its reproducibility is shown in duplicates of bulk cells with close to perfect correlation (R = 0.97–0.99). At a low 1 Mb of clean reads, msRRBS provides highly consistent coverage of CpG islands and promoters, outperforming the conventional methods with orders of magnitude reduction in cost. Here, we use this method to characterize the distinct methylation patterns and cellular heterogeneity of six cell lines, plus leukemia and hepatocellular carcinoma models. Taking 4 h of hands-on time, msRRBS offers a unique, highly efficient approach for dissecting methylation heterogeneity in a variety of multicellular systems.
IMP: bridging the gap for medicinal plant genomics
Authors: Chen Tong , Yang Mei , Cui Guanghong , Tang Jinfu , Shen Ye , Liu Juan , Yuan Yuan , Guo Juan , Huang Luqi 
Published: October 2023

Abstract
Medicinal plants have garnered significant attention in ethnomedicine and traditional medicine due to their potential antitumor, anti-inflammatory and antioxidant properties. Recent advancements in genome sequencing and synthetic biology have revitalized interest in natural products. Despite the availability of sequenced genomes and transcriptomes of these plants, the absence of publicly accessible gene annotations and tabular formatted gene expression data has hindered their effective utilization. To address this pressing issue, we have developed IMP (Integrated Medicinal Plantomics), a freely accessible platform at https://www.bic.ac.cn/IMP. IMP curated a total of 8 565 672 genes for 84 high-quality genome assemblies, and 2156 transcriptome sequencing samples encompassing various organs, tissues, developmental stages and stimulations. With the integrated 10 analysis modules, users could simply examine gene annotations, sequences, functions, distributions and expressions in IMP in a one-stop mode. We firmly believe that IMP will play a vital role in enhancing the understanding of molecular metabolic pathways in medicinal plants or plants with medicinal benefits, thereby driving advancements in synthetic biology, and facilitating the exploration of natural sources for valuable chemical constituents like drug discovery and drug production.
Long non-coding RNA generated fromCDKN1Agene by alternative polyadenylation regulates p21 expression during DNA damage response
Authors: Murphy Michael R , Ramadei Anthony , Doymaz Ahmet , Varriano Sophia , Natelson Devorah M , Yu Amy , Aktas Sera , Mazzeo Marie , Mazzeo Michael , Zakusilo George , Kleiman Frida E 
Published: October 2023

AbstractAlternative Polyadenylation (APA) is an emerging mechanism for dynamic changes in gene expression. Previously, we described widespread APA occurrence in introns during the DNA damage response (DDR). Here, we show that a DDR-activated APA event occurs in the first intron of CDKN1A, inducing an alternate last exon-containing lncRNA. We named this lncRNA SPUD (Selective Polyadenylation Upon DNA Damage). SPUD localizes to polysomes in the cytoplasm and is detectable as multiple isoforms in available high-throughput studies. SPUD has low abundance compared to the CDKN1A full-length isoform under non-stress conditions, and SPUD is induced in cancer and normal cells under a variety of DNA damaging conditions in part through p53. The RNA binding protein HuR binds to and promotes the stability of SPUD precursor RNA. SPUD induction increases p21 protein, but not mRNA levels, affecting p21 functions in cell-cycle, CDK2 expression and cell growth. Like CDKN1A full-length isoform, SPUD can bind two competitive p21 translational regulators, the inhibitor calreticulin and the activator CUGBP1; SPUD alters their association with CDKN1A full-length in a DDR-dependent manner, promoting CDKN1A translation. Together, these results show a new regulatory mechanism by which a lncRNA controls p21 expression post-transcriptionally, highlighting lncRNA relevance in DDR progression and cell-cycle.
Selective targeting of parallel G-quadruplex structure using L-RNA aptamer
Authors: Ji Danyang , Yuan Jia-Hao , Chen Shuo-Bin , Tan Jia-Heng , Kwok Chun Kit 
Published: October 2023

Abstract
G-quadruplexes (G4) are special nucleic acid structures with diverse conformational polymorphisms. Selective targeting of G-quadruplex conformations and regulating their biological functions provide promising therapeutic intervention. Despite the large repertoire of G4-binding tools, only a limited number of them can specifically target a particular G4 conformation. Here, we introduce a novel method, G4-SELEX-Seq and report the development of the first L-RNA aptamer, L-Apt12-6, with high binding selectivity to parallel G4 over other nucleic acid structures. Using parallel dG4 c-kit 1 as an example, we demonstrate the strong binding affinity between L-Apt12-6 and c-kit 1 dG4 in vitro and in cells, and notably report the applications of L-Apt12-6 in controlling DNA replication and gene expression. Our results suggest that L-Apt12-6 is a valuable tool for targeting parallel G-quadruplex conformation and regulating G4-mediated biological processes. Furthermore, G4-SELEX-Seq can be used as a general platform for G4-targeting L-RNA aptamers selection and should be applicable to other nucleic acid structures.
TargetGene: a comprehensive database of cell-type-specific target genes for genetic variants
Authors: Lin Shiqi , Wu Song , Zhao Wei , Fang Zhanjie , Kang Hongen , Liu Xinxuan , Pan Siyu , Yu Fudong , Bao Yiming , Jia Peilin 
Published: October 2023

Abstract
Annotating genetic variants to their target genes is of great importance in unraveling the causal variants and genetic mechanisms that underlie complex diseases. However, disease-associated genetic variants are often located in non-coding regions and manifest context-specific effects, making it challenging to accurately identify the target genes and regulatory mechanisms. Here, we present TargetGene (https://ngdc.cncb.ac.cn/targetgene/), a comprehensive database reporting target genes for human genetic variants from various aspects. Specifically, we collected a comprehensive catalog of multi-omics data at the single-cell and bulk levels and from various human tissues, cell types and developmental stages. To facilitate the identification of Single Nucleotide Polymorphism (SNP)-to-gene connections, we have implemented multiple analytical tools based on chromatin co-accessibility, 3D interaction, enhancer activities and quantitative trait loci, among others. We applied the pipeline to evaluate variants from nearly 1300 Genome-wide association studies (GWAS) and assembled a comprehensive atlas of multiscale regulation of genetic variants. TargetGene is equipped with user-friendly web interfaces that enable intuitive searching, navigation and browsing through the results. Overall, TargetGene provides a unique resource to empower researchers to study the regulatory mechanisms of genetic variants in complex human traits.
HervD Atlas: a curated knowledgebase of associations between human endogenous retroviruses and diseases
Authors: Li Cuidan , Qian Qiheng , Yan Chenghao , Lu Mingming , Li Lin , Li Pan , Fan Zhuojing , Lei Wenyan , Shang Kang , Wang Peihan , Wang Jie , Lu Tianyi , Huang Yuting , Yang Hongwei , Wei Haobin , Han Jingwan , Xiao Jingfa , Chen Fei 
Published: October 2023

Abstract
Human endogenous retroviruses (HERVs), as remnants of ancient exogenous retrovirus infected and integrated into germ cells, comprise ∼8% of the human genome. These HERVs have been implicated in numerous diseases, and extensive research has been conducted to uncover their specific roles. Despite these efforts, a comprehensive source of HERV-disease association still needs to be added. To address this gap, we introduce the HervD Atlas (https://ngdc.cncb.ac.cn/hervd/), an integrated knowledgebase of HERV-disease associations manually curated from all related published literature. In the current version, HervD Atlas collects 60 726 HERV-disease associations from 254 publications (out of 4692 screened literature), covering 21 790 HERVs (21 049 HERV-Terms and 741 HERV-Elements) belonging to six types, 149 diseases and 610 related/affected genes. Notably, an interactive knowledge graph that systematically integrates all the HERV-disease associations and corresponding affected genes into a comprehensive network provides a powerful tool to uncover and deduce the complex interplay between HERVs and diseases. The HervD Atlas also features a user-friendly web interface that allows efficient browsing, searching, and downloading of all association information, research metadata, and annotation information. Overall, the HervD Atlas is an essential resource for comprehensive, up-to-date knowledge on HERV-disease research, potentially facilitating the development of novel HERV-associated diagnostic and therapeutic strategies.
BRD9-mediated control of the TGF-β/Activin/Nodal pathway regulates self-renewal and differentiation of human embryonic stem cells and progression of cancer cells
Authors: Wang Xuepeng , Song Chengcheng , Ye Ying , Gu Yashi , Li Xuemei , Chen Peixin , Leng Dongliang , Xiao Jing , Wu Hao , Xie Sisi , Liu Weiwei , Zhao Qi , Chen Di , Chen Xi , Wu Qiang , Chen Guokai , Zhang Wensheng 
Published: October 2023

Abstract
Bromodomain-containing protein 9 (BRD9) is a specific subunit of the non-canonical SWI/SNF (ncBAF) chromatin-remodeling complex, whose function in human embryonic stem cells (hESCs) remains unclear. Here, we demonstrate that impaired BRD9 function reduces the self-renewal capacity of hESCs and alters their differentiation potential. Specifically, BRD9 depletion inhibits meso-endoderm differentiation while promoting neural ectoderm differentiation. Notably, supplementation of NODAL, TGF-β, Activin A or WNT3A rescues the differentiation defects caused by BRD9 loss. Mechanistically, BRD9 forms a complex with BRD4, SMAD2/3, β-CATENIN and P300, which regulates the expression of pluripotency genes and the activity of TGF-β/Nodal/Activin and Wnt signaling pathways. This is achieved by regulating the deposition of H3K27ac on associated genes, thus maintaining and directing hESC differentiation. BRD9-mediated regulation of the TGF-β/Activin/Nodal pathway is also demonstrated in the development of pancreatic and breast cancer cells. In summary, our study highlights the crucial role of BRD9 in the regulation of hESC self-renewal and differentiation, as well as its participation in the progression of pancreatic and breast cancers.
FusionNeoAntigen: a resource of fusion gene-specific neoantigens
Authors: Kumar Himansu , Luo Ruihan , Wen Jianguo , Yang Chengyuan , Zhou Xiaobo , Kim Pora 
Published: October 2023

Abstract
Among the diverse sources of neoantigens (i.e. single-nucleotide variants (SNVs), insertions or deletions (Indels) and fusion genes), fusion gene-derived neoantigens are generally more immunogenic, have multiple targets per mutation and are more widely distributed across various cancer types. Therefore, fusion gene-derived neoantigens are a potential source of highly immunogenic neoantigens and hold great promise for cancer immunotherapy. However, the lack of fusion protein sequence resources and knowledge prevents this application. We introduce ‘FusionNeoAntigen’, a dedicated resource for fusion-specific neoantigens, accessible at https://compbio.uth.edu/FusionNeoAntigen. In this resource, we provide fusion gene breakpoint crossing neoantigens focused on ∼43K fusion proteins of ∼16K in-frame fusion genes from FusionGDB2.0. FusionNeoAntigen provides fusion gene information, corresponding fusion protein sequences, fusion breakpoint peptide sequences, fusion gene-derived neoantigen prediction, virtual screening between fusion breakpoint peptides having potential fusion neoantigens and human leucocyte antigens (HLAs), fusion breakpoint RNA/protein sequences for developing vaccines, information on samples with fusion-specific neoantigen, potential CAR-T targetable cell-surface fusion proteins and literature curation. FusionNeoAntigen will help to develop fusion gene-based immunotherapies. We will report all potential fusion-specific neoantigens from all possible open reading frames of ∼120K human fusion genes in future versions.
ICEberg 3.0: functional categorization and analysis of the integrative and conjugative elements in bacteria
Authors: Wang Meng , Liu Guitian , Liu Meng , Tai Cui , Deng Zixin , Song Jiangning , Ou Hong-Yu 
Published: October 2023

Abstract
ICEberg 3.0 (https://tool2-mml.sjtu.edu.cn/ICEberg3/) is an upgraded database that provides comprehensive insights into bacterial integrative and conjugative elements (ICEs). In comparison to the previous version, three key enhancements were introduced: First, through text mining and manual curation, it now encompasses details of 2065 ICEs, 607 IMEs and 275 CIMEs, including 430 with experimental support. Secondly, ICEberg 3.0 systematically categorizes cargo gene functions of ICEs into six groups based on literature curation and predictive analysis, providing a profound understanding of ICEs’diverse biological traits. The cargo gene prediction pipeline is integrated into the online tool ICEfinder 2.0. Finally, ICEberg 3.0 aids the analysis and exploration of ICEs from the human microbiome. Extracted and manually curated from 2405 distinct human microbiome samples, the database comprises 1386 putative ICEs, offering insights into the complex dynamics of Bacteria-ICE-Cargo networks within the human microbiome. With the recent updates, ICEberg 3.0 enhances its capability to unravel the intricacies of ICE biology, particularly in the characterization and understanding of cargo gene functions and ICE interactions within the microbiome. This enhancement may facilitate the investigation of the dynamic landscape of ICE biology and its implications for microbial communities.