Genome researchPub Date : 2025-05-07DOI: 10.1101/gr.279878.124
Paras Verma, Deeksha Thakur, Deepanshi Awasthi, Shashi Bhushan Pandit
{"title":"Exon nomenclature and classification of transcripts (ENACT) provides a systematic framework to annotate exon attributes","authors":"Paras Verma, Deeksha Thakur, Deepanshi Awasthi, Shashi Bhushan Pandit","doi":"10.1101/gr.279878.124","DOIUrl":"https://doi.org/10.1101/gr.279878.124","url":null,"abstract":"Isoform diversity is known to enhance a gene's functional repertoire by producing protein variants with distinct functional implications. Despite numerous studies on transcriptome diversifying processes (alternative splicing/transcription), understanding their extent and correlated impact on proteome diversity remains limited owing to dearth of subsequent proteogenomic consequences. To coalesce the genomic information embedded in exons with isoform sequences, we present an innovative framework, “Exon Nomenclature and Classification of Transcripts” (ENACT). This centralizes exonic loci such that protein sequence information is integrated (onto the available/annotated or new transcripts) while enabling tracking and assessing splice-site variability through unique yielded descriptors. The resulting annotation from the ENACT framework enables exon features to be tractable, facilitating a systematic analysis of isoform diversity. Our findings and case studies unveil systemic exon inclusion roles in regulating diversity in coding region. Correspondingly, annotation of protein-coding genes and associated transcripts from <em>C. elegans</em>, <em>D. melanogaster</em>, <em>D. rerio</em>, <em>M. musculus</em>, and <em>H. sapiens</em> are publicly accessible in a dedicated resource.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"43 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143920039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Genome researchPub Date : 2025-05-02DOI: 10.1101/gr.279771.124
Vishvak Raghavan, Yumin Zheng, Yue Li, Jun Ding
{"title":"Harnessing agent-based frameworks in CellAgentChat to unravel cell-cell interactions from single-cell and spatial transcriptomics","authors":"Vishvak Raghavan, Yumin Zheng, Yue Li, Jun Ding","doi":"10.1101/gr.279771.124","DOIUrl":"https://doi.org/10.1101/gr.279771.124","url":null,"abstract":"Understanding cell-cell interactions (CCIs) is essential yet challenging due to the inherent intricacy and diversity of cellular dynamics. Existing approaches often analyze global patterns of CCIs using statistical frameworks, missing the nuances of individual cell behavior due to their focus on aggregate data. This makes them insensitive in complex environments where the detailed dynamics of cell interactions matter. We introduce CellAgentChat, an agent-based model (ABM) designed to decipher CCIs from single-cell RNA sequencing and spatial transcriptomics data. This approach models biological systems as collections of autonomous agents governed by biologically inspired principles and rules. Validated across eight diverse single-cell datasets, CellAgentChat demonstrates its effectiveness in detecting intricate signaling events across different cell populations. Moreover, CellAgentChat offers the ability to generate animated visualizations of single-cell interactions and provides flexibility in modifying agent behavior rules, facilitating thorough exploration of both close and distant cellular communications. Furthermore, CellAgentChat leverages ABM features to enable intuitive in silico perturbations via agent rule modifications, facilitating the development of novel intervention strategies. This ABM method unlocks an in-depth understanding of cellular signaling interactions across various biological contexts, thereby enhancing in silico studies for cellular communication-based therapies.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"6 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143898285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Genome researchPub Date : 2025-04-25DOI: 10.1101/gr.279609.124
Chenbo Gong, Yicheng Huang, Mengmeng Liu, Yong Zhou, Yinwei Xu, Nahed Mohammed, Xintong Qiao, Andrea Zuccolo, Weibo Xie, Rod A. Wing, Jianwei Zhang, Fei Zhou, Yongjun Lin
{"title":"Continuous infiltration and evolutionary trajectory of nuclear organelle DNA in Oryza","authors":"Chenbo Gong, Yicheng Huang, Mengmeng Liu, Yong Zhou, Yinwei Xu, Nahed Mohammed, Xintong Qiao, Andrea Zuccolo, Weibo Xie, Rod A. Wing, Jianwei Zhang, Fei Zhou, Yongjun Lin","doi":"10.1101/gr.279609.124","DOIUrl":"https://doi.org/10.1101/gr.279609.124","url":null,"abstract":"Transfer of chloroplast or mitochondrial DNA into the nuclear genome is a common phenomenon in many species. However, little is known about the evolutionary fate and mechanism of transfer of organellar DNA sequences in higher plants. We observe abundant insertions of organelle DNA into the nuclear genomes of 22 genome assemblies across seven <em>Oryza</em> species and further categorize nuclear organelle DNA (NORG) into 3406 orthologous groups. Analysis of the whole-genome resequencing data from 3458 <em>O. sativa</em>, <em>O. glaberrima</em>, and <em>O. barthii</em> accessions indicate that NORGs have intra- and inter-population variability owing to sequence loss and transposon insertion during evolution. Our results also suggest that NORGs have been continuously produced during the evolution of <em>Oryza</em>, and both double-strand break repair pathways and replication-based mechanisms play important roles in integrating organelle DNA into the nuclear genome. Further investigation indicates that complex NORGs are formed through single mutational events before or during the insertion process via ligation of multiple plastid and/or mitochondrial DNA with each other. In summary, this work provides novel insights into the process of endosymbiotic DNA transfer and its role in reshaping genome variation and plant genome evolution.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"24 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143876248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Genome researchPub Date : 2025-04-24DOI: 10.1101/gr.280082.124
Keegan S Krick, Marissa Maroni, Erica Korb, Kristen Lynch, Elizabeth A Heller
{"title":"Meta-analysis of activated neurons reveals dynamic regulation of diverse classes of alternative splicing","authors":"Keegan S Krick, Marissa Maroni, Erica Korb, Kristen Lynch, Elizabeth A Heller","doi":"10.1101/gr.280082.124","DOIUrl":"https://doi.org/10.1101/gr.280082.124","url":null,"abstract":"Activity-dependent gene expression in neurons is well-established, yet few studies have examined activity-dependent alternative splicing. Alternative splicing regulates >95% of genes and is essential to diverse neuronal functions, including synapse development and calcium channel diversity. Alternative splicing is regulated by the expression and activity of RNA-binding proteins and through changes in the local chromatin environment. To date, most analyses of activity-dependent alternative splicing are focus primarily on microexons, a small subclass of neuron-specific exons. To broaden knowledge of activity-dependent alternative splicing in neurons, we analyzed five independent RNA-seq studies to identify splicing events that consistently respond to potassium chloride (KCl) depolarization. We found that the majority of activity-dependent exons become less included upon activation, are basally constitutive, are not microexons, and reside in genes that are not differentially expressed after KCl treatment. Functionally, alternative splicing of RNA processing machinery and regulators precedes splicing of genes related to neuronal function. Given recent advances in elucidating chromatin-mediated alternative splicing in brain, we explored the coincident regulation of histone modifications over activity-dependent exons. We found KCl-dependent changes in H3K36me3 and H4K20me1, both enriched in active gene bodies, over a subset of KCl-dependent exons, suggesting coordination of activity-dependent histone modification and alternative splicing. Together, these findings identify a diverse class of activity-dependent alternative splicing and describes the temporality and features of its regulation in cultured neurons.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"5 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143866550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Genome researchPub Date : 2025-04-24DOI: 10.1101/gr.280161.124
Siyu Xie, Jun Li, Wanyan Chen, Lydia Fong, Chunhua Huang, Yan Feng, Qingbo Ai, Mian Zhao, Judith Mank, Hua Wu
{"title":"Extreme heterochiasmy and high rates of sex-reversed recombination result in large yet homomorphic sex chromosomes in the Emei moustache toad","authors":"Siyu Xie, Jun Li, Wanyan Chen, Lydia Fong, Chunhua Huang, Yan Feng, Qingbo Ai, Mian Zhao, Judith Mank, Hua Wu","doi":"10.1101/gr.280161.124","DOIUrl":"https://doi.org/10.1101/gr.280161.124","url":null,"abstract":"Unlike the highly degenerated sex chromosomes in birds and mammals, many amphibians possess homomorphic sex chromosomes, which may result from high rates of sex chromosome turnover and/or occasional recombination between the X and Y (or Z and W) Chromosomes. Yet the molecular basis for maintaining homomorphy remains elusive, particularly the power of rare recombination events to arrest sex chromosome divergence. Here, we identified sex chromosomes of the Emei moustache toad and examined potential mechanisms of maintaining homomorphy. Although the sex chromosomes are homomorphic, we observed an extensive region of X-Y genetic differentiation, spanning ~349 Mb, among the largest known to date in vertebrates. Despite this large size, and the assumption that inversions catalyze recombination suppression between the X and Y Chromosomes, we found little evidence of XY structural variation. Using a high-density linkage map, we revealed that the large region of X-Y divergence was likely due to the emergence of sex determining factors in the region of ancestrally low male recombination. Population genetic data showed high rates of sex reversed XY type females, and recombination between the X and Y Chromosomes in these individuals help maintain the integrity of sequence and gene expression on the Y Chromosome. Finally, we revealed modest sexualization of gene expression within the sex chromosomes, and identified candidate genes involved in gonadal development. Our results not only show remarkable maintenance of vast sex differentiated regions under ancestral low recombination, but also emphasize the sustaining power of X-Y recombination for homomorphic chromosomes over large genomic regions.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"20 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143866549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Genome researchPub Date : 2025-04-22DOI: 10.1101/gr.279857.124
Lulu Yan, Jinyu Cheng, Qing Nie, Xiaoqiang Sun
{"title":"Dissecting multilayer cell-cell communications with signaling feedback loops from spatial transcriptomics data","authors":"Lulu Yan, Jinyu Cheng, Qing Nie, Xiaoqiang Sun","doi":"10.1101/gr.279857.124","DOIUrl":"https://doi.org/10.1101/gr.279857.124","url":null,"abstract":"The emergence of spatial transcriptomics (ST) provides unprecedented opportunities to better decipher cell-cell communication (CCC). How to integrate spatial information and complex signaling mechanisms to infer functional CCC, however, remains a major challenge. Here, we present stMLnet, a method that takes into account spatial information and multilayer signaling regulations to identify signaling feedback loops within multilayer CCCs from ST data. To this end, stMLnet quantifies spatially dependent ligand-receptor signaling activity based on diffusion and mass action models and maps it to intracellular targets. We benchmark stMLnet against seven representative existing methods and found that stMLnet performs better in both intercellular ligand-receptor inference and intracellular target genes prediction. We apply stMLnet to analyze data from diverse spatial transcriptomics techniques like seqFISH+, Slide-seq v2, MERFISH, and Stereo-seq, verifying its robustness and scalability on ST data with varying spatial resolutions and gene coverages. Particularly, stMLnet reveals multilayer signaling feedback loops underlying the inflammatory response in ST data of COVID-19-infected lung tissue. Our study provides an effective tool for dissecting multilayer ligand/receptor-target regulations and multicellular signaling circuits from ST data, which can advance understanding of the mechanistic and functional roles of spatial CCC.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"24 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143862874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Genome researchPub Date : 2025-04-22DOI: 10.1101/gr.280387.124
Jingjing Zhao, Fotis A Baltoumas, Maxwell A Konnaris, Ioannis Mouratidis, Zhe Liu, Jasmine Sims, Vikram Agarwal, Georgios A Pavlopoulos, Ilias Georgakopoulos-Soares, Nadav Ahituv
{"title":"MPRAbase a Massively Parallel Reporter Assay database","authors":"Jingjing Zhao, Fotis A Baltoumas, Maxwell A Konnaris, Ioannis Mouratidis, Zhe Liu, Jasmine Sims, Vikram Agarwal, Georgios A Pavlopoulos, Ilias Georgakopoulos-Soares, Nadav Ahituv","doi":"10.1101/gr.280387.124","DOIUrl":"https://doi.org/10.1101/gr.280387.124","url":null,"abstract":"Massively parallel reporter assays (MPRAs) represent a set of high-throughput technologies that measure the functional effects of thousands of sequences/variants on gene regulatory activity. There are several different variations of MPRA technology and they are used for numerous applications, including regulatory element discovery, variant effect measurement, saturation mutagenesis, synthetic regulatory element generation or characterization of evolutionary gene regulatory differences. Despite their many designs and uses, there is no comprehensive database that incorporates the results of these experiments. To address this, we developed MPRAbase, a manually curated database that currently harbors 130 experiments, encompassing 17,718,677 elements tested across 35 cell types and 4 organisms. The MPRAbase web interface serves as a centralized user-friendly repository to examine online the activity of regulatory elements across cell types and organisms, and to download MPRA data for independent analysis.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"104 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143862876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Genome researchPub Date : 2025-04-22DOI: 10.1101/gr.279080.124
Abigail L. Lind, Nathan A McDonald, Elias R Gerrick, Ami S Bhatt, Katherine Pollard
{"title":"Contiguous and complete assemblies of Blastocystis gut microbiome-associated protists reveal evolutionary diversification to host ecology","authors":"Abigail L. Lind, Nathan A McDonald, Elias R Gerrick, Ami S Bhatt, Katherine Pollard","doi":"10.1101/gr.279080.124","DOIUrl":"https://doi.org/10.1101/gr.279080.124","url":null,"abstract":"<em>Blastocystis</em>, an obligate host-associated protist, is the most common microbial eukaryote in the human gut and is widely distributed across vertebrate hosts. The evolutionary transition of <em>Blastocystis</em> from its free-living stramenopile ancestors to a radiation of host-associated organisms is poorly understood. To explore this, we cultured and sequenced eight strains representing the significant phylogenetic diversity of the genus using long-read, short-read, and Hi-C DNA sequencing, alongside gene annotation and RNA sequencing. Comparative genomic analyses revealed significant variation in gene content and genome structure across <em>Blastocystis</em>. Notably, three strains from herbivorous tortoises, phylogenetically distant from human subtypes, have markedly larger genomes with longer introns and intergenic regions, and retain canonical stop codons absent in the human-associated strains. Despite these genetic differences, all eight isolates exhibit gene losses linked to the reduced cellular complexity of <em>Blastocystis</em>, including losses of cilia and flagella genes, microtubule motor genes, and signal transduction genes. Isolates from herbivorous tortoises contained higher numbers of plant carbohydrate-metabolizing enzymes, suggesting that like gut bacteria, these protists ferment plant material in the host gut. We find evidence that some of these carbohydrate-metabolizing enzymes were horizontally acquired from bacteria, indicating that horizontal gene transfer is an ongoing process in <em>Blastocystis</em> that has contributed to host-related adaptation. Together, these results highlight substantial genetic and metabolic diversity within the <em>Blastocystis</em> genus, indicating different lineages of <em>Blastocystis</em> have varied ecological roles in the host gut.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"4 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143862875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Genome researchPub Date : 2025-04-15DOI: 10.1101/gr.279652.124
Olga M. Sigalova, Mattia Forneris, Frosina Stojanovska, Bingqing Zhao, Rebecca R. Viales, Adam Rabinowitz, Fayrouz Hammal, Benoît Ballester, Judith B. Zaugg, Eileen E.M. Furlong
{"title":"Integrating genetic variation with deep learning provides context for variants impacting transcription factor binding during embryogenesis","authors":"Olga M. Sigalova, Mattia Forneris, Frosina Stojanovska, Bingqing Zhao, Rebecca R. Viales, Adam Rabinowitz, Fayrouz Hammal, Benoît Ballester, Judith B. Zaugg, Eileen E.M. Furlong","doi":"10.1101/gr.279652.124","DOIUrl":"https://doi.org/10.1101/gr.279652.124","url":null,"abstract":"Understanding how genetic variation impacts transcription factor (TF) binding remains a major challenge, limiting our ability to model disease-associated variants. Here, we used a highly controlled system of F<sub>1</sub> crosses with extensive genetic diversity to profile allele-specific binding of four TFs at several time points during <em>Drosophila</em> embryogenesis. Using a combined haplotype test, we identified 9%–18% of TF-bound regions impacted by genetic variation even for essential regulators. By expanding WASP (a tool for allele-specific read mapping) to examine indels, we increased detection of allelically imbalanced peaks by 30%–50%. This fine-grained “mutagenesis” can reconstruct functionalized binding motifs for all factors. To prioritize causal variants, we trained a convolutional neural network (Basenji) to accurately predict binding from DNA sequence. The model can also predict measured allelic imbalance for strong effect variants, providing a mechanistic interpretation for how the variant impacts binding. This reveals unexpected relationships between TFs, including potential cooperative pairs, and mechanisms of tissue-specific recruitment of the ubiquitous factor CTCF.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"16 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143837030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Genome researchPub Date : 2025-04-15DOI: 10.1101/gr.280377.124
Adam H. Freedman, Timothy B. Sackton
{"title":"Building better genome annotations across the tree of life","authors":"Adam H. Freedman, Timothy B. Sackton","doi":"10.1101/gr.280377.124","DOIUrl":"https://doi.org/10.1101/gr.280377.124","url":null,"abstract":"Recent technological advances in long-read DNA sequencing accompanied by reduction in costs have made the production of genome assemblies financially achievable and computationally feasible, such that genome assembly no longer represents the major hurdle to evolutionary analysis for most nonmodel organisms. Now, the more difficult challenge is to properly annotate a draft genome assembly once it has been constructed. The primary challenge to annotations is how to select from the myriad gene prediction tools that are currently available, determine what kinds of data are necessary to generate high-quality annotations, and evaluate the quality of the annotation. To determine which methods perform the best and to determine whether the inclusion of RNA-seq data is necessary to obtain a high-quality annotation, we generated annotations with 12 different methods for 21 different species spanning vertebrates, plants, and insects. We found that the annotation transfer method TOGA, BRAKER3, and the RNA-seq assembler StringTie were consistently top performers across a variety of metrics including BUSCO recovery, CDS length, and false-positive rate, with the exception that TOGA performed less well in some monocots with respect to BUSCO recovery. The choice of which of the top-performing methods will depend upon the feasibility of whole-genome alignment, availability of RNA-seq data, importance of capturing noncoding parts of the transcriptome, and, when whole-genome alignment is not feasible, the relative performance in BUSCO recovery between BRAKER3 and StringTie. When whole-genome alignment is not feasible, inclusion of RNA-seq data will lead to substantial improvements to genome annotations.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"6 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143837025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}