Pub Date : 2024-08-01DOI: 10.1186/s13059-024-03349-w
Irzam Sarfraz, Yichen Wang, Amulya Shastry, Wei Kheng Teh, Artem Sokolov, Brian R. Herb, Heather H. Creasy, Isaac Virshup, Ruben Dries, Kylee Degatano, Anup Mahurkar, Daniel J. Schnell, Pedro Madrigal, Jason Hilton, Nils Gehlenborg, Timothy Tickle, Joshua D. Campbell
Many datasets are being produced by consortia that seek to characterize healthy and disease tissues at single-cell resolution. While biospecimen and experimental information is often captured, detailed metadata standards related to data matrices and analysis workflows are currently lacking. To address this, we develop the matrix and analysis metadata standards (MAMS) to serve as a resource for data centers, repositories, and tool developers. We define metadata fields for matrices and parameters commonly utilized in analytical workflows and developed the rmams package to extract MAMS from single-cell objects. Overall, MAMS promotes the harmonization, integration, and reproducibility of single-cell data across platforms.
{"title":"MAMS: matrix and analysis metadata standards to facilitate harmonization and reproducibility of single-cell data","authors":"Irzam Sarfraz, Yichen Wang, Amulya Shastry, Wei Kheng Teh, Artem Sokolov, Brian R. Herb, Heather H. Creasy, Isaac Virshup, Ruben Dries, Kylee Degatano, Anup Mahurkar, Daniel J. Schnell, Pedro Madrigal, Jason Hilton, Nils Gehlenborg, Timothy Tickle, Joshua D. Campbell","doi":"10.1186/s13059-024-03349-w","DOIUrl":"https://doi.org/10.1186/s13059-024-03349-w","url":null,"abstract":"Many datasets are being produced by consortia that seek to characterize healthy and disease tissues at single-cell resolution. While biospecimen and experimental information is often captured, detailed metadata standards related to data matrices and analysis workflows are currently lacking. To address this, we develop the matrix and analysis metadata standards (MAMS) to serve as a resource for data centers, repositories, and tool developers. We define metadata fields for matrices and parameters commonly utilized in analytical workflows and developed the rmams package to extract MAMS from single-cell objects. Overall, MAMS promotes the harmonization, integration, and reproducibility of single-cell data across platforms.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"74 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141862136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01DOI: 10.1186/s13059-024-03339-y
Jia Li, Yu Shyr, Qi Liu
Typical clustering methods for single-cell and spatial transcriptomics struggle to identify rare cell types, while approaches tailored to detect rare cell types gain this ability at the cost of poorer performance for grouping abundant ones. Here, we develop aKNNO to simultaneously identify abundant and rare cell types based on an adaptive k-nearest neighbor graph with optimization. Benchmarking on 38 simulated and 20 single-cell and spatial transcriptomics datasets demonstrates that aKNNO identifies both abundant and rare cell types more accurately than general and specialized methods. Using only gene expression aKNNO maps abundant and rare cells more precisely compared to integrative approaches.
单细胞和空间转录组学的典型聚类方法难以识别稀有细胞类型，而为检测稀有细胞类型量身定制的方法获得了这种能力，但代价是对丰富细胞类型的分组性能较差。在此，我们开发了 KNNO，基于优化的自适应 k 近邻图同时识别丰富和稀有细胞类型。在 38 个模拟数据集和 20 个单细胞及空间转录组学数据集上进行的基准测试表明，与一般方法和专门方法相比，aKNNO 能更准确地识别丰富细胞类型和稀有细胞类型。与综合方法相比，仅使用基因表达，KNNO 就能更精确地绘制丰富和稀有细胞的图谱。
{"title":"aKNNO: single-cell and spatial transcriptomics clustering with an optimized adaptive k-nearest neighbor graph","authors":"Jia Li, Yu Shyr, Qi Liu","doi":"10.1186/s13059-024-03339-y","DOIUrl":"https://doi.org/10.1186/s13059-024-03339-y","url":null,"abstract":"Typical clustering methods for single-cell and spatial transcriptomics struggle to identify rare cell types, while approaches tailored to detect rare cell types gain this ability at the cost of poorer performance for grouping abundant ones. Here, we develop aKNNO to simultaneously identify abundant and rare cell types based on an adaptive k-nearest neighbor graph with optimization. Benchmarking on 38 simulated and 20 single-cell and spatial transcriptomics datasets demonstrates that aKNNO identifies both abundant and rare cell types more accurately than general and specialized methods. Using only gene expression aKNNO maps abundant and rare cells more precisely compared to integrative approaches.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"28 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141862138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01DOI: 10.1186/s13059-024-03346-z
Kero Guynes, Luke A. Sarre, Allan M. Carrillo-Baltodano, Billie E. Davies, Lan Xu, Yan Liang, Francisco M. Martín-Zamora, Paul J. Hurd, Alex de Mendoza, José M. Martín-Durán
DNA methylation in the form of 5-methylcytosine (5mC) is the most abundant base modification in animals. However, 5mC levels vary widely across taxa. While vertebrate genomes are hypermethylated, in most invertebrates, 5mC concentrates on constantly and highly transcribed genes (gene body methylation; GbM) and, in some species, on transposable elements (TEs), a pattern known as “mosaic”. Yet, the role and developmental dynamics of 5mC and how these explain interspecies differences in DNA methylation patterns remain poorly understood, especially in Spiralia, a large clade of invertebrates comprising nearly half of the animal phyla. Here, we generate base-resolution methylomes for three species with distinct genomic features and phylogenetic positions in Annelida, a major spiralian phylum. All possible 5mC patterns occur in annelids, from typical invertebrate intermediate levels in a mosaic distribution to hypermethylation and methylation loss. GbM is common to annelids with 5mC, and methylation differences across species are explained by taxon-specific transcriptional dynamics or the presence of intronic TEs. Notably, the link between GbM and transcription decays during development, alongside a gradual and global, age-dependent demethylation in adult stages. Additionally, reducing 5mC levels with cytidine analogs during early development impairs normal embryogenesis and reactivates TEs in the annelid Owenia fusiformis. Our study indicates that global epigenetic erosion during development and aging is an ancestral feature of bilateral animals. However, the tight link between transcription and gene body methylation is likely more important in early embryonic stages, and 5mC-mediated TE silencing probably emerged convergently across animal lineages.
{"title":"Annelid methylomes reveal ancestral developmental and aging-associated epigenetic erosion across Bilateria","authors":"Kero Guynes, Luke A. Sarre, Allan M. Carrillo-Baltodano, Billie E. Davies, Lan Xu, Yan Liang, Francisco M. Martín-Zamora, Paul J. Hurd, Alex de Mendoza, José M. Martín-Durán","doi":"10.1186/s13059-024-03346-z","DOIUrl":"https://doi.org/10.1186/s13059-024-03346-z","url":null,"abstract":"DNA methylation in the form of 5-methylcytosine (5mC) is the most abundant base modification in animals. However, 5mC levels vary widely across taxa. While vertebrate genomes are hypermethylated, in most invertebrates, 5mC concentrates on constantly and highly transcribed genes (gene body methylation; GbM) and, in some species, on transposable elements (TEs), a pattern known as “mosaic”. Yet, the role and developmental dynamics of 5mC and how these explain interspecies differences in DNA methylation patterns remain poorly understood, especially in Spiralia, a large clade of invertebrates comprising nearly half of the animal phyla. Here, we generate base-resolution methylomes for three species with distinct genomic features and phylogenetic positions in Annelida, a major spiralian phylum. All possible 5mC patterns occur in annelids, from typical invertebrate intermediate levels in a mosaic distribution to hypermethylation and methylation loss. GbM is common to annelids with 5mC, and methylation differences across species are explained by taxon-specific transcriptional dynamics or the presence of intronic TEs. Notably, the link between GbM and transcription decays during development, alongside a gradual and global, age-dependent demethylation in adult stages. Additionally, reducing 5mC levels with cytidine analogs during early development impairs normal embryogenesis and reactivates TEs in the annelid Owenia fusiformis. Our study indicates that global epigenetic erosion during development and aging is an ancestral feature of bilateral animals. However, the tight link between transcription and gene body methylation is likely more important in early embryonic stages, and 5mC-mediated TE silencing probably emerged convergently across animal lineages.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"39 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141862137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01Epub Date: 2022-03-10DOI: 10.1089/cbr.2021.0371
Xiao Fu, Zhongchao Duan, Xin Lu, Yingyu Zhu, Yuanyuan Ren, Wei Zhang, Xiaoming Sun, Lin Ge, Jie Yang
Background: Radiotherapy is one of the most effective therapeutic strategies for cervical cancer patients, although radioresistance-mediated residual and recurrent tumors are the main cause of treatment failure. However, the mechanism of tumor radioresistance is still elusive. DNA damage response pathways are key determinants of radioresistance. The purpose of this study was to investigate the role and mechanism of SND1 in radioresistance of cervical cancer. Methods: A stable HeLa cell line with SND1 knockout (HeLa-KO) was generated through a modified CRISPR/Cas9 double-nicking gene editing system. The stable CaSki cell lines with SND1 knockdown (CaSki-Ctrl, CaSki-SND1-sh-1, CaSki-SND1-sh-2) were constructed through lentivirus transfection with the pSil-SND1-sh-1 and pSil-SND1-sh-2 plasmids. Results: It was observed that SND1 deficiency significantly increased the radiosensitivity of cervical cancer cells. It was also found that silencing SND1 promotes radiation-induced apoptosis. Significantly, the cells with a loss of SND1 function exhibited inefficient ataxia telangiectasia mutated pathway activation, subsequently impairing DNA repair and G2/M checkpoint arrest. In addition, threonine 103 is an important phosphorylation site of SND1 under DNA damaging stress. Conclusion: Collectively, the results of this study reveal a potent radiosensitizing effect of silencing SND1 or T103 mutation on cervical cancer cells, providing novel insights into potential therapeutic strategies for cervical cancer treatment.
{"title":"SND1 Promotes Radioresistance in Cervical Cancer Cells by Targeting the DNA Damage Response.","authors":"Xiao Fu, Zhongchao Duan, Xin Lu, Yingyu Zhu, Yuanyuan Ren, Wei Zhang, Xiaoming Sun, Lin Ge, Jie Yang","doi":"10.1089/cbr.2021.0371","DOIUrl":"10.1089/cbr.2021.0371","url":null,"abstract":"<p><p><b><i>Background:</i></b> Radiotherapy is one of the most effective therapeutic strategies for cervical cancer patients, although radioresistance-mediated residual and recurrent tumors are the main cause of treatment failure. However, the mechanism of tumor radioresistance is still elusive. DNA damage response pathways are key determinants of radioresistance. The purpose of this study was to investigate the role and mechanism of SND1 in radioresistance of cervical cancer. <b><i>Methods:</i></b> A stable HeLa cell line with SND1 knockout (HeLa-KO) was generated through a modified CRISPR/Cas9 double-nicking gene editing system. The stable CaSki cell lines with SND1 knockdown (CaSki-Ctrl, CaSki-SND1-sh-1, CaSki-SND1-sh-2) were constructed through lentivirus transfection with the pSil-SND1-sh-1 and pSil-SND1-sh-2 plasmids. <b><i>Results:</i></b> It was observed that SND1 deficiency significantly increased the radiosensitivity of cervical cancer cells. It was also found that silencing SND1 promotes radiation-induced apoptosis. Significantly, the cells with a loss of SND1 function exhibited inefficient ataxia telangiectasia mutated pathway activation, subsequently impairing DNA repair and G2/M checkpoint arrest. In addition, threonine 103 is an important phosphorylation site of SND1 under DNA damaging stress. <b><i>Conclusion:</i></b> Collectively, the results of this study reveal a potent radiosensitizing effect of silencing SND1 or T103 mutation on cervical cancer cells, providing novel insights into potential therapeutic strategies for cervical cancer treatment.</p>","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"5 1","pages":"425-434"},"PeriodicalIF":2.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87962338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-30DOI: 10.1186/s13059-024-03342-3
Yanhong Liu, Pan Liu, Lifeng Gao, Yushan Li, Xueni Ren, Jizeng Jia, Lei Wang, Xu Zheng, Yiping Tong, Hongcui Pei, Zefu Lu
Winter wheat undergoes vernalization, a process activated by prolonged exposure to low temperatures. During this phase, flowering signals are generated and transported to the apical meristems, stimulating the transition to the inflorescence meristem while inhibiting tiller bud elongation. Although some vernalization genes have been identified, the key cis-regulatory elements and precise mechanisms governing this process in wheat remain largely unknown. In this study, we construct extensive epigenomic and transcriptomic profiling across multiple tissues—leaf, axillary bud, and shoot apex—during the vernalization of winter wheat. Epigenetic modifications play a crucial role in eliciting tissue-specific responses and sub-genome-divergent expressions during vernalization. Notably, we observe that H3K27me3 primarily regulates vernalization-induced genes and has limited influence on vernalization-repressed genes. The integration of these datasets enables the identification of 10,600 putative vernalization-related regulatory elements including distal accessible chromatin regions (ACRs) situated 30Kb upstream of VRN3, contributing to the construction of a comprehensive regulatory network. Furthermore, we discover that TaSPL7/15, integral components of the aging-related flowering pathway, interact with the VRN1 promoter and VRN3 distal regulatory elements. These interactions finely regulate their expressions, consequently impacting the vernalization process and flowering. Our study offers critical insights into wheat vernalization’s epigenomic dynamics and identifies the putative regulatory elements crucial for developing wheat germplasm with varied vernalization characteristics. It also establishes a vernalization-related transcriptional network, and uncovers that TaSPL7/15 from the aging pathway participates in vernalization by directly binding to the VRN1 promoter and VRN3 distal regulatory elements.
{"title":"Epigenomic identification of vernalization cis-regulatory elements in winter wheat","authors":"Yanhong Liu, Pan Liu, Lifeng Gao, Yushan Li, Xueni Ren, Jizeng Jia, Lei Wang, Xu Zheng, Yiping Tong, Hongcui Pei, Zefu Lu","doi":"10.1186/s13059-024-03342-3","DOIUrl":"https://doi.org/10.1186/s13059-024-03342-3","url":null,"abstract":"Winter wheat undergoes vernalization, a process activated by prolonged exposure to low temperatures. During this phase, flowering signals are generated and transported to the apical meristems, stimulating the transition to the inflorescence meristem while inhibiting tiller bud elongation. Although some vernalization genes have been identified, the key cis-regulatory elements and precise mechanisms governing this process in wheat remain largely unknown. In this study, we construct extensive epigenomic and transcriptomic profiling across multiple tissues—leaf, axillary bud, and shoot apex—during the vernalization of winter wheat. Epigenetic modifications play a crucial role in eliciting tissue-specific responses and sub-genome-divergent expressions during vernalization. Notably, we observe that H3K27me3 primarily regulates vernalization-induced genes and has limited influence on vernalization-repressed genes. The integration of these datasets enables the identification of 10,600 putative vernalization-related regulatory elements including distal accessible chromatin regions (ACRs) situated 30Kb upstream of VRN3, contributing to the construction of a comprehensive regulatory network. Furthermore, we discover that TaSPL7/15, integral components of the aging-related flowering pathway, interact with the VRN1 promoter and VRN3 distal regulatory elements. These interactions finely regulate their expressions, consequently impacting the vernalization process and flowering. Our study offers critical insights into wheat vernalization’s epigenomic dynamics and identifies the putative regulatory elements crucial for developing wheat germplasm with varied vernalization characteristics. It also establishes a vernalization-related transcriptional network, and uncovers that TaSPL7/15 from the aging pathway participates in vernalization by directly binding to the VRN1 promoter and VRN3 distal regulatory elements.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"48 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141794568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-30DOI: 10.1186/s13059-024-03341-4
Jose M Serradell, Jose M Lorenzo-Salazar, Carlos Flores, Oscar Lao, David Comas
Background: North African human populations present a complex demographic scenario due to the presence of an autochthonous genetic component and population substructure, plus extensive gene flow from the Middle East, Europe, and sub-Saharan Africa.
Results: We conducted a comprehensive analysis of 364 genomes to construct detailed demographic models for the North African region, encompassing its two primary ethnic groups, the Arab and Amazigh populations. This was achieved through an Approximate Bayesian Computation with Deep Learning (ABC-DL) framework and a novel algorithm called Genetic Programming for Population Genetics (GP4PG). This innovative approach enabled us to effectively model intricate demographic scenarios, utilizing a subset of 16 whole genomes at > 30X coverage. The demographic model suggested by GP4PG exhibited a closer alignment with the observed data compared to the ABC-DL model. Both point to a back-to-Africa origin of North African individuals and a close relationship with Eurasian populations. Results support different origins for Amazigh and Arab populations, with Amazigh populations originating back in Epipaleolithic times, while GP4PG supports Arabization as the main source of Middle Eastern ancestry. The GP4PG model includes population substructure in surrounding populations (sub-Saharan Africa and Middle East) with continuous decaying gene flow after population split. Contrary to ABC-DL, the best GP4PG model does not require pulses of admixture from surrounding populations into North Africa pointing to soft splits as drivers of divergence in North Africa.
Conclusions: We have built a demographic model on North Africa that points to a back-to-Africa expansion and a differential origin between Arab and Amazigh populations.
{"title":"Modelling the demographic history of human North African genomes points to a recent soft split divergence between populations.","authors":"Jose M Serradell, Jose M Lorenzo-Salazar, Carlos Flores, Oscar Lao, David Comas","doi":"10.1186/s13059-024-03341-4","DOIUrl":"10.1186/s13059-024-03341-4","url":null,"abstract":"<p><strong>Background: </strong>North African human populations present a complex demographic scenario due to the presence of an autochthonous genetic component and population substructure, plus extensive gene flow from the Middle East, Europe, and sub-Saharan Africa.</p><p><strong>Results: </strong>We conducted a comprehensive analysis of 364 genomes to construct detailed demographic models for the North African region, encompassing its two primary ethnic groups, the Arab and Amazigh populations. This was achieved through an Approximate Bayesian Computation with Deep Learning (ABC-DL) framework and a novel algorithm called Genetic Programming for Population Genetics (GP4PG). This innovative approach enabled us to effectively model intricate demographic scenarios, utilizing a subset of 16 whole genomes at > 30X coverage. The demographic model suggested by GP4PG exhibited a closer alignment with the observed data compared to the ABC-DL model. Both point to a back-to-Africa origin of North African individuals and a close relationship with Eurasian populations. Results support different origins for Amazigh and Arab populations, with Amazigh populations originating back in Epipaleolithic times, while GP4PG supports Arabization as the main source of Middle Eastern ancestry. The GP4PG model includes population substructure in surrounding populations (sub-Saharan Africa and Middle East) with continuous decaying gene flow after population split. Contrary to ABC-DL, the best GP4PG model does not require pulses of admixture from surrounding populations into North Africa pointing to soft splits as drivers of divergence in North Africa.</p><p><strong>Conclusions: </strong>We have built a demographic model on North Africa that points to a back-to-Africa expansion and a differential origin between Arab and Amazigh populations.</p>","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"25 1","pages":"201"},"PeriodicalIF":10.1,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11290046/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141855331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-29DOI: 10.1186/s13059-024-03338-z
Xiuhui Yang, Koren K. Mann, Hao Wu, Jun Ding
Single-cell multi-omics data reveal complex cellular states, providing significant insights into cellular dynamics and disease. Yet, integration of multi-omics data presents challenges. Some modalities have not reached the robustness or clarity of established transcriptomics. Coupled with data scarcity for less established modalities and integration intricacies, these challenges limit our ability to maximize single-cell omics benefits. We introduce scCross, a tool leveraging variational autoencoders, generative adversarial networks, and the mutual nearest neighbors (MNN) technique for modality alignment. By enabling single-cell cross-modal data generation, multi-omics data simulation, and in silico cellular perturbations, scCross enhances the utility of single-cell multi-omics studies.
{"title":"scCross: a deep generative model for unifying single-cell multi-omics with seamless integration, cross-modal generation, and in silico exploration","authors":"Xiuhui Yang, Koren K. Mann, Hao Wu, Jun Ding","doi":"10.1186/s13059-024-03338-z","DOIUrl":"https://doi.org/10.1186/s13059-024-03338-z","url":null,"abstract":"Single-cell multi-omics data reveal complex cellular states, providing significant insights into cellular dynamics and disease. Yet, integration of multi-omics data presents challenges. Some modalities have not reached the robustness or clarity of established transcriptomics. Coupled with data scarcity for less established modalities and integration intricacies, these challenges limit our ability to maximize single-cell omics benefits. We introduce scCross, a tool leveraging variational autoencoders, generative adversarial networks, and the mutual nearest neighbors (MNN) technique for modality alignment. By enabling single-cell cross-modal data generation, multi-omics data simulation, and in silico cellular perturbations, scCross enhances the utility of single-cell multi-omics studies.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"48 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141790927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-29DOI: 10.1186/s13059-024-03323-6
Yuyao Song, Guillermo Parada, Jimmy Tsz Hang Lee, Martin Hemberg
Single-cell RNA-seq (scRNA-seq) is widely used for transcriptome profiling, but most analyses focus on gene-level events, with less attention devoted to alternative splicing. Here, we present scASfind, a novel computational method to allow for quantitative analysis of cell type-specific splicing events using full-length scRNA-seq data. ScASfind utilizes an efficient data structure to store the percent spliced-in value for each splicing event. This makes it possible to exhaustively search for patterns among all differential splicing events, allowing us to identify marker events, mutually exclusive events, and events involving large blocks of exons that are specific to one or more cell types.
{"title":"Mining alternative splicing patterns in scRNA-seq data using scASfind","authors":"Yuyao Song, Guillermo Parada, Jimmy Tsz Hang Lee, Martin Hemberg","doi":"10.1186/s13059-024-03323-6","DOIUrl":"https://doi.org/10.1186/s13059-024-03323-6","url":null,"abstract":"Single-cell RNA-seq (scRNA-seq) is widely used for transcriptome profiling, but most analyses focus on gene-level events, with less attention devoted to alternative splicing. Here, we present scASfind, a novel computational method to allow for quantitative analysis of cell type-specific splicing events using full-length scRNA-seq data. ScASfind utilizes an efficient data structure to store the percent spliced-in value for each splicing event. This makes it possible to exhaustively search for patterns among all differential splicing events, allowing us to identify marker events, mutually exclusive events, and events involving large blocks of exons that are specific to one or more cell types.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"73 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141791153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-29DOI: 10.1186/s13059-024-03348-x
Bao Yang, Zengdong Tan, Jiayu Yan, Ke Zhang, Zhewen Ouyang, Ruyi Fan, Yefei Lu, Yuting Zhang, Xuan Yao, Hu Zhao, Xuemin Wang, Shaoping Lu, Liang Guo
Phosphorus is a macronutrient necessary for plant growth and development and its availability and efficient use affect crop yields. Leaves are the largest tissue that uses phosphorus in plants, and membrane phospholipids are the main source of cellular phosphorus usage. Here we identify a key process for plant cellular phosphorus recycling mediated by membrane phospholipid hydrolysis during leaf senescence. Our results indicate that over 90% of lipid phosphorus, accounting for more than one-third of total cellular phosphorus, is recycled from senescent leaves before falling off the plants. Nonspecific phospholipase C4 (NPC4) and phospholipase Dζ2 (PLDζ2) are highly induced during leaf senescence, and knockouts of PLDζ2 and NPC4 decrease the loss of membrane phospholipids and delay leaf senescence. Conversely, overexpression of PLDζ2 and NPC4 accelerates the loss of phospholipids and leaf senescence, promoting phosphorus remobilization from senescent leaves to young tissues and plant growth. We also show that this phosphorus recycling process in senescent leaves mediated by membrane phospholipid hydrolysis is conserved in plants. These results indicate that PLDζ2- and NPC4-mediated membrane phospholipid hydrolysis promotes phosphorus remobilization from senescent leaves to growing tissues and that the phospholipid hydrolysis-mediated phosphorus recycling improves phosphorus use efficiency in plants.
{"title":"Phospholipase-mediated phosphate recycling during plant leaf senescence","authors":"Bao Yang, Zengdong Tan, Jiayu Yan, Ke Zhang, Zhewen Ouyang, Ruyi Fan, Yefei Lu, Yuting Zhang, Xuan Yao, Hu Zhao, Xuemin Wang, Shaoping Lu, Liang Guo","doi":"10.1186/s13059-024-03348-x","DOIUrl":"https://doi.org/10.1186/s13059-024-03348-x","url":null,"abstract":"Phosphorus is a macronutrient necessary for plant growth and development and its availability and efficient use affect crop yields. Leaves are the largest tissue that uses phosphorus in plants, and membrane phospholipids are the main source of cellular phosphorus usage. Here we identify a key process for plant cellular phosphorus recycling mediated by membrane phospholipid hydrolysis during leaf senescence. Our results indicate that over 90% of lipid phosphorus, accounting for more than one-third of total cellular phosphorus, is recycled from senescent leaves before falling off the plants. Nonspecific phospholipase C4 (NPC4) and phospholipase Dζ2 (PLDζ2) are highly induced during leaf senescence, and knockouts of PLDζ2 and NPC4 decrease the loss of membrane phospholipids and delay leaf senescence. Conversely, overexpression of PLDζ2 and NPC4 accelerates the loss of phospholipids and leaf senescence, promoting phosphorus remobilization from senescent leaves to young tissues and plant growth. We also show that this phosphorus recycling process in senescent leaves mediated by membrane phospholipid hydrolysis is conserved in plants. These results indicate that PLDζ2- and NPC4-mediated membrane phospholipid hydrolysis promotes phosphorus remobilization from senescent leaves to growing tissues and that the phospholipid hydrolysis-mediated phosphorus recycling improves phosphorus use efficiency in plants.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"15 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141791151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-27DOI: 10.1186/s13059-024-03344-1
Xue Li, Bo Zhu, Yue Lu, Feng Zhao, Qian Liu, Jiahao Wang, Miaomiao Ye, Siyuan Chen, Junwei Nie, Lizhong Xiong, Yu Zhao, Changyin Wu, Dao-Xiu Zhou
<p><b>Author Correction: Genome Biol 25, 84 (2024)</b></p><p><b>https://doi.org/10.1186/s13059-024-03222-w</b></p><br/><p>Following publication of the original article [1], the authors identified an error in Fig. 2. In Fig. 2B, a wild type pollen picture was wrongly used to represent cmt3b pollens that in fact are of wild type phenotype.</p><p>The incorrect and correct Fig. 2 is published in this correction article and the original article [1] has been updated.</p><p>Incorrect figure:</p><br/><figure><figcaption><b data-test="figure-caption-text">Fig. 2</b></figcaption><picture><source srcset="//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs13059-024-03344-1/MediaObjects/13059_2024_3344_Fig1_HTML.png?as=webp" type="image/webp"/><img alt="figure 1" aria-describedby="Fig1" height="989" loading="lazy" src="//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs13059-024-03344-1/MediaObjects/13059_2024_3344_Fig1_HTML.png" width="685"/></picture><p>Effects of <i>cmt3a</i> and <i>cmt3b</i> mutations on DNA methylation in meiocyte, microspore and sperm. <b>a</b> Transcript levels in FPKM of rice CMT3a and CMT3b in seedling (Se), roots (Ro), meiocyte (Me), unicellular microspore (UM), sperm (S), egg (E), zygote (Z), endosperm nuclei (En, 1.5 days after fertilization) and globular embryo (GE, 3 days after fertilization) from RNA-seq data. The sperm (Kit-S) in Kitaake background was reported by Anderson et al., (2013). <b>b</b> The pollen grains of wild type and <i>cmt3a</i> and <i>cmt3b</i> mutants were I2-KI stained. Bars = 50 μm. <b>c</b> Violin plots comparing overall cytosine methylation levels of wild type and <i>cmt3a</i> and <i>cmt3b</i> mutant meiocyte (Me), unicellular microspore (UM) and sperm (S). The average methylation levels (white dots) and median values (black bars) in transposable elements (TE) are shown. Values of the methylomes are averages from the two replicates. <b>d</b> Number of differential methylated regions (DMR) in <i>cmt3a</i> and <i>cmt3b</i> relative to wild type. Relative portions in TE (> 500 bp), TEG, gene, and Intergenic regions are indicated by different colors. <b>e</b> Venn diagrams showing overlapping of hypo-CHG DMRs in <i>cmt3a</i> and <i>cmt3b</i> meiocyte (left) and sperm (right) relative to wild type cells. <b>f</b> Box plots of DNA methylation levels of hypo-CHG DMRs in meiocyte (Me) versus microspore (UM) (upper) and sperm (S) relative to microspore (UM) (lower) in wild type, <i>cmt3a</i> (3a) and <i>cmt3b</i> (3b) cells. The significance was calculated with multiple comparison tests. Different letters on top of the bars indicate a significant difference (<i>p</i> < 0.05). <b>g</b> Genome Browser screen captures showing high CHG methylation sites in microspore relative to meiocyte and sperm decreased in cmt3b mutants (highlighted by grey)</p><span>Full size image</span><svg aria-hidden="true" focusable="false" height="16" role="img" width="16"><use xlink:href="#ic
{"title":"Author Correction: DNA methylation remodeling and the functional implication during male gametogenesis in rice","authors":"Xue Li, Bo Zhu, Yue Lu, Feng Zhao, Qian Liu, Jiahao Wang, Miaomiao Ye, Siyuan Chen, Junwei Nie, Lizhong Xiong, Yu Zhao, Changyin Wu, Dao-Xiu Zhou","doi":"10.1186/s13059-024-03344-1","DOIUrl":"https://doi.org/10.1186/s13059-024-03344-1","url":null,"abstract":"<p><b>Author Correction: Genome Biol 25, 84 (2024)</b></p><p><b>https://doi.org/10.1186/s13059-024-03222-w</b></p><br/><p>Following publication of the original article [1], the authors identified an error in Fig. 2. In Fig. 2B, a wild type pollen picture was wrongly used to represent cmt3b pollens that in fact are of wild type phenotype.</p><p>The incorrect and correct Fig. 2 is published in this correction article and the original article [1] has been updated.</p><p>Incorrect figure:</p><br/><figure><figcaption><b data-test=\"figure-caption-text\">Fig. 2</b></figcaption><picture><source srcset=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs13059-024-03344-1/MediaObjects/13059_2024_3344_Fig1_HTML.png?as=webp\" type=\"image/webp\"/><img alt=\"figure 1\" aria-describedby=\"Fig1\" height=\"989\" loading=\"lazy\" src=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs13059-024-03344-1/MediaObjects/13059_2024_3344_Fig1_HTML.png\" width=\"685\"/></picture><p>Effects of <i>cmt3a</i> and <i>cmt3b</i> mutations on DNA methylation in meiocyte, microspore and sperm. <b>a</b> Transcript levels in FPKM of rice CMT3a and CMT3b in seedling (Se), roots (Ro), meiocyte (Me), unicellular microspore (UM), sperm (S), egg (E), zygote (Z), endosperm nuclei (En, 1.5 days after fertilization) and globular embryo (GE, 3 days after fertilization) from RNA-seq data. The sperm (Kit-S) in Kitaake background was reported by Anderson et al., (2013). <b>b</b> The pollen grains of wild type and <i>cmt3a</i> and <i>cmt3b</i> mutants were I2-KI stained. Bars = 50 μm. <b>c</b> Violin plots comparing overall cytosine methylation levels of wild type and <i>cmt3a</i> and <i>cmt3b</i> mutant meiocyte (Me), unicellular microspore (UM) and sperm (S). The average methylation levels (white dots) and median values (black bars) in transposable elements (TE) are shown. Values of the methylomes are averages from the two replicates. <b>d</b> Number of differential methylated regions (DMR) in <i>cmt3a</i> and <i>cmt3b</i> relative to wild type. Relative portions in TE (> 500 bp), TEG, gene, and Intergenic regions are indicated by different colors. <b>e</b> Venn diagrams showing overlapping of hypo-CHG DMRs in <i>cmt3a</i> and <i>cmt3b</i> meiocyte (left) and sperm (right) relative to wild type cells. <b>f</b> Box plots of DNA methylation levels of hypo-CHG DMRs in meiocyte (Me) versus microspore (UM) (upper) and sperm (S) relative to microspore (UM) (lower) in wild type, <i>cmt3a</i> (3a) and <i>cmt3b</i> (3b) cells. The significance was calculated with multiple comparison tests. Different letters on top of the bars indicate a significant difference (<i>p</i> < 0.05). <b>g</b> Genome Browser screen captures showing high CHG methylation sites in microspore relative to meiocyte and sperm decreased in cmt3b mutants (highlighted by grey)</p><span>Full size image</span><svg aria-hidden=\"true\" focusable=\"false\" height=\"16\" role=\"img\" width=\"16\"><use xlink:href=\"#ic","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"56 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141768536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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