Genome Biology最新文献_第4页

Guidelines for releasing a variant effect predictor 变异效应预测器发布指南

IF 12.3 1区生物学

Genome Biology Pub Date : 2025-04-15 DOI: 10.1186/s13059-025-03572-z

Benjamin J. Livesey, Mihaly Badonyi, Mafalda Dias, Jonathan Frazer, Sushant Kumar, Kresten Lindorff-Larsen, David M. McCandlish, Rose Orenbuch, Courtney A. Shearer, Lara Muffley, Julia Foreman, Andrew M. Glazer, Ben Lehner, Debora S. Marks, Frederick P. Roth, Alan F. Rubin, Lea M. Starita, Joseph A. Marsh

引用次数: 0

Post-cleavage target residence determines asymmetry in non-homologous end joining of Cas12a-induced DNA double strand breaks 切割后靶点驻留决定了cas12a诱导的DNA双链断裂非同源端连接的不对称性

IF 12.3 1区生物学

Genome Biology Pub Date : 2025-04-14 DOI: 10.1186/s13059-025-03567-w

Ruo-Dan Chen, Yi Yang, Kun-Ming Liu, Jing-Zhen Hu, Yi-Li Feng, Chun-Yi Yang, Rui-Rui Jiang, Si-Cheng Liu, Yue Wang, Ping-An Han, Ru-Gang Tian, Yu-Long Wang, Shi-Ming Xu, An-Yong Xie

{"title":"Post-cleavage target residence determines asymmetry in non-homologous end joining of Cas12a-induced DNA double strand breaks","authors":"Ruo-Dan Chen, Yi Yang, Kun-Ming Liu, Jing-Zhen Hu, Yi-Li Feng, Chun-Yi Yang, Rui-Rui Jiang, Si-Cheng Liu, Yue Wang, Ping-An Han, Ru-Gang Tian, Yu-Long Wang, Shi-Ming Xu, An-Yong Xie","doi":"10.1186/s13059-025-03567-w","DOIUrl":"https://doi.org/10.1186/s13059-025-03567-w","url":null,"abstract":"After Cas12a cleaves its DNA target, it generates a DNA double strand break (DSB) with two compatible 5′-staggered ends. The Cas12a-gRNA complex remains at the protospacer adjacent motif (PAM)-proximal end (PPE) while releasing the PAM-distal end (PDE). The effects of this asymmetric retention on DSB repair are currently unknown. Post-cleavage retention of LbCas12a at PPEs suppresses the recruitment of classical non-homologous end joining (c-NHEJ) core factors, leading to longer deletions at PPEs compared to PDEs. This asymmetry in c-NHEJ engagement results in approximately tenfold more accurate ligation between two compatible PDEs induced by paired LbCas12a than ligation involving a compatible PPE. Moreover, ligation to a given end of SpCas9-induced DSBs demonstrates more efficient ligation with a PDE from Cas12a-induced DSBs than with a PPE. In LbCas12a-induced NHEJ-mediated targeted integration, only two compatible PDEs from LbCas12a-induced DSBs—one from donor templates and the other from target sites—promote accurate and directional ligation. Based on these findings, we developed a strategy called Cas12a-induced PDE ligation (CIPDEL) for NHEJ-mediated efficient and precise gene correction and insertion. The asymmetric retention of CRISPR-LbCas12a at DSB ends suppresses c-NHEJ at PPEs, not at PDEs. This unique repair mechanism can be utilized in the CIPDEL strategy, offering a potentially better alternative for homology-directed targeted integration.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"60 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143827649","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}

引用次数: 0

Genomic evidence for low genetic diversity but purging of strong deleterious variants in snow leopards 基因组证据表明，雪豹的遗传多样性低，但清除了强烈的有害变异

IF 12.3 1区生物学

Genome Biology Pub Date : 2025-04-14 DOI: 10.1186/s13059-025-03555-0

Lin Yang, Hong Jin, Qien Yang, Andrey Poyarkov, Miroslav Korablev, Viatcheslav Rozhnov, Junjie Shao, Qiaomei Fu, Jose Antonio Hernandez-Blanco, Xiangjiang Zhan, Li Yu, Dmitry Alexandrov, Qingyan Dai, Bariushaa Munkhtsog, Xin Du, Bayaraa Munkhtsog, Liqing Ma, Wanlin Chen, Sergei Malykh, Yipeng Jin, Shunfu He, Tongzuo Zhang, Guosheng Wu, Yonghong Shi, Fuwen Wei, Yibo Hu

{"title":"Genomic evidence for low genetic diversity but purging of strong deleterious variants in snow leopards","authors":"Lin Yang, Hong Jin, Qien Yang, Andrey Poyarkov, Miroslav Korablev, Viatcheslav Rozhnov, Junjie Shao, Qiaomei Fu, Jose Antonio Hernandez-Blanco, Xiangjiang Zhan, Li Yu, Dmitry Alexandrov, Qingyan Dai, Bariushaa Munkhtsog, Xin Du, Bayaraa Munkhtsog, Liqing Ma, Wanlin Chen, Sergei Malykh, Yipeng Jin, Shunfu He, Tongzuo Zhang, Guosheng Wu, Yonghong Shi, Fuwen Wei, Yibo Hu","doi":"10.1186/s13059-025-03555-0","DOIUrl":"https://doi.org/10.1186/s13059-025-03555-0","url":null,"abstract":"Long-term persistence of species with low genetic diversity is the focus of widespread attention in conservation biology. The snow leopard, Panthera uncia, is a big cat from high-alpine regions of Asia. However, its subspecies taxonomy, evolutionary history, evolutionary potential, and survival strategy remain unclear, which greatly hampers their conservation. We sequence a high-quality chromosome-level genome of the snow leopard and the genomes of 52 wild snow leopards. Population genomics reveal the existence of two large genetic lineages in global snow leopards, the northern and southern lineages, supported by the biogeography. The Last Glacial Maximum drove the divergence of two lineages. Microclimate differences and large rivers between the western and central Himalayas likely maintain the differentiation of two lineages. EPAS1 is positively selected in the southern lineage with almost fixed amino acid substitutions and shows an increased allele frequency with elevation. Compared to the southern lineage, the northern lineage exhibits a lower level of genomic diversity and higher levels of inbreeding and genetic load, consistent with its recent population decline. We find that snow leopards have extremely low genomic diversity and higher inbreeding than other Carnivora species; however, strong deleterious mutations have been effectively purged in snow leopards by historical population bottlenecks and inbreeding, which may be a vital genetic mechanism for their population survival and viability. Our findings reveal the survival strategy of a species with low genetic diversity and highlight the importance of unveiling both genetic diversity and genetic burden for the conservation of threatened species.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"75 6 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143827650","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}

引用次数: 0

Extracellular vesicle-derived miRNA-mediated cell–cell communication inference for single-cell transcriptomic data with miRTalk 细胞外囊泡衍生的mirna介导的细胞-细胞通讯推断与miRTalk单细胞转录组数据

IF 12.3 1区生物学

Genome Biology Pub Date : 2025-04-14 DOI: 10.1186/s13059-025-03566-x

Xin Shao, Lingqi Yu, Chengyu Li, Jingyang Qian, Xinyu Yang, Haihong Yang, Jie Liao, Xueru Fan, Xiao Xu, Xiaohui Fan

引用次数: 0

Spatiotemporal transcriptomics reveals key gene regulation for grain yield and quality in wheat 时空转录组学揭示小麦谷物产量和品质的关键基因调控

IF 12.3 1区生物学

Genome Biology Pub Date : 2025-04-11 DOI: 10.1186/s13059-025-03569-8

Xiaohui Li, Yiman Wan, Dongzhi Wang, Xingguo Li, Jiajie Wu, Jun Xiao, Kunming Chen, Xue Han, Yuan Chen

{"title":"Spatiotemporal transcriptomics reveals key gene regulation for grain yield and quality in wheat","authors":"Xiaohui Li, Yiman Wan, Dongzhi Wang, Xingguo Li, Jiajie Wu, Jun Xiao, Kunming Chen, Xue Han, Yuan Chen","doi":"10.1186/s13059-025-03569-8","DOIUrl":"https://doi.org/10.1186/s13059-025-03569-8","url":null,"abstract":"Cereal grain size and quality are critical agronomic traits in crop production. Wheat grain development is governed by intricate regulatory networks that require precise spatiotemporal coordination of gene expression to establish functional compartments in different cell types. Here, we perform a spatial transcriptomics study covering the early stages of wheat grain development, from 4 to 12 days after pollination. We classify the grain into 10 distinct cell types and identify 192 marker genes associated with them. WGCNA analysis reveals that highly expressed genes in different cell types exhibit distinct enrichment patterns, significantly influencing grain development and filling. Through co-expression and motif analyses, we identify a specific group of genes that may regulate wheat grain development, including TaABI3-B1, a transcription factor specifically expressed in the embryo and surrounding endosperm, which negatively affects embryo and grain size. This study presents a comprehensive spatiotemporal transcriptional dataset for understanding wheat grain development. Additionally, it identifies key genetic resources with potential applications for improving wheat yield.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"74 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143819553","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}

引用次数: 0

TF Profiler: a transcription factor inference method that broadly measures transcription factor activity and identifies mechanistically distinct networks TF Profiler：一种转录因子推断方法，广泛测量转录因子活性并识别机械上不同的网络

IF 12.3 1区生物学

Genome Biology Pub Date : 2025-04-09 DOI: 10.1186/s13059-025-03545-2

Taylor Jones, Rutendo F. Sigauke, Lynn Sanford, Dylan J. Taatjes, Mary A. Allen, Robin D. Dowell

引用次数: 0

Filtering cells with high mitochondrial content depletes viable metabolically altered malignant cell populations in cancer single-cell studies 在癌症单细胞研究中，具有高线粒体含量的过滤细胞消耗了代谢改变的恶性细胞群

IF 12.3 1区生物学

Genome Biology Pub Date : 2025-04-09 DOI: 10.1186/s13059-025-03559-w

Josephine Yates, Agnieszka Kraft, Valentina Boeva

{"title":"Filtering cells with high mitochondrial content depletes viable metabolically altered malignant cell populations in cancer single-cell studies","authors":"Josephine Yates, Agnieszka Kraft, Valentina Boeva","doi":"10.1186/s13059-025-03559-w","DOIUrl":"https://doi.org/10.1186/s13059-025-03559-w","url":null,"abstract":"Single-cell transcriptomics has transformed our understanding of cellular diversity, yet noise from technical artifacts and low-quality cells can obscure key biological signals. A common practice is filtering out cells with a high percentage of mitochondrial RNA counts (pctMT), typically indicative of cell death. However, commonly used filtering thresholds, primarily derived from studies on healthy tissues, may be overly stringent for malignant cells, which often naturally exhibit higher baseline mitochondrial gene expression. We examine nine public single-cell RNA-seq datasets from various cancers, including 441,445 cells from 134 patients, and public spatial transcriptomics data, assessing the viability of malignant cells with high pctMT. Our analysis reveals that malignant cells exhibit significantly higher pctMT than nonmalignant cells, without a notable increase in dissociation-induced stress scores. Malignant cells with high pctMT show metabolic dysregulation, including increased xenobiotic metabolism, relevant to therapeutic response. Analysis of pctMT in cancer cell lines further reveals links to drug resistance. We also observe associations between pctMT and malignant cell transcriptional heterogeneity, as well as patient clinical features. This study provides insights into the functional characteristics of malignant cells with elevated pctMT, challenging current quality control practices in tumor single-cell RNA-seq analyses and offering potential improvements in data interpretation for future cancer studies.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"97 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143813725","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}

引用次数: 0

MIDAA: deep archetypal analysis for interpretable multi-omic data integration based on biological principles MIDAA：基于生物学原理的可解释多组数据集成的深度原型分析

IF 12.3 1区生物学

Genome Biology Pub Date : 2025-04-08 DOI: 10.1186/s13059-025-03530-9

Salvatore Milite, Giulio Caravagna, Andrea Sottoriva

引用次数: 0

The histone acetyltransferase CBP participates in regulating the DNA damage response through ATM after double-strand breaks 组蛋白乙酰转移酶CBP通过ATM参与调控双链断裂后的DNA损伤反应

IF 12.3 1区生物学

Genome Biology Pub Date : 2025-04-08 DOI: 10.1186/s13059-025-03528-3

Wafaa S. Ramadan, Samrein B. M. Ahmed, Iman M. Talaat, Lama Lozon, Soraya Mouffak, Timo Gemoll, Wael Y. Mansour, Raafat El-Awady

{"title":"The histone acetyltransferase CBP participates in regulating the DNA damage response through ATM after double-strand breaks","authors":"Wafaa S. Ramadan, Samrein B. M. Ahmed, Iman M. Talaat, Lama Lozon, Soraya Mouffak, Timo Gemoll, Wael Y. Mansour, Raafat El-Awady","doi":"10.1186/s13059-025-03528-3","DOIUrl":"https://doi.org/10.1186/s13059-025-03528-3","url":null,"abstract":"Spatial and temporal control of DNA damage response pathways after DNA damage is crucial for maintenance of genomic stability. Ataxia telangiectasia mutated (ATM) protein plays a central role in DNA damage response pathways. The chain of events following induction of DNA damage that results in full activation of ATM is still evolving. Here we set out to explore the role of CREB-binding protein (CBP), a histone acetyltransferase (HAT), in DNA damage response, particularly in the ATM activation pathway. In response to DNA damage, CBP is stabilized and is recruited at sites of DNA double-strand breaks where it acetylates ATM and promotes its kinase activity. Cells deficient in CBP display an impairment in DNA double-strand break repair and high sensitivity to chemo- and radiotherapy. Importantly, re-expressing CBP’s HAT domain in CBP-deficient cells restores the DNA repair capability, demonstrating the essential role of CBP’s HAT domain in repairing DNA double-strand breaks. Together, our findings shed the light on CBP as a key participant in the ATM activation pathway and in the subsequent repair of DNA double-strand breaks, which may serve as a potential target to modulate the cellular response to DNA damaging agents in cancer. ","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"6 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143797775","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}

引用次数: 0

Missing cell types in single-cell references impact deconvolution of bulk data but are detectable 单细胞参考中缺失的细胞类型影响大量数据的反褶积，但可以检测到

IF 12.3 1区生物学

Genome Biology Pub Date : 2025-04-07 DOI: 10.1186/s13059-025-03506-9

Adriana Ivich, Natalie R. Davidson, Laurie Grieshober, Weishan Li, Stephanie C. Hicks, Jennifer A. Doherty, Casey S. Greene

{"title":"Missing cell types in single-cell references impact deconvolution of bulk data but are detectable","authors":"Adriana Ivich, Natalie R. Davidson, Laurie Grieshober, Weishan Li, Stephanie C. Hicks, Jennifer A. Doherty, Casey S. Greene","doi":"10.1186/s13059-025-03506-9","DOIUrl":"https://doi.org/10.1186/s13059-025-03506-9","url":null,"abstract":"Advancements in RNA sequencing have expanded our ability to study gene expression profiles of biological samples in bulk tissue and single cells. Deconvolution of bulk data with single-cell references provides the ability to study relative cell-type proportions, but most methods assume a reference is present for every cell type in bulk data. This is not true in all circumstances—cell types can be missing in single-cell profiles for many reasons. In this study, we examine the impact of missing cell types on deconvolution methods. Using paired single-cell and single-nucleus data, we simulate realistic scenarios where cell types are missing since single-nucleus RNA sequencing is able to capture cell types that would otherwise be missing in a single-cell counterpart. Single-nucleus sequencing captures cell types absent in single-cell counterparts, allowing us to study their effects on deconvolution. We evaluate three different methods and find that performance is influenced by both the number and similarity of missing cell types. Additionally, missing cell-type profiles can be recovered from residuals using a simple non-negative matrix factorization strategy. We also analyzed real bulk data of cancerous and non-cancerous samples. We observe results consistent with simulation, namely that expression patterns from cell types likely to be missing appear present in residuals. We expect our results to provide a starting point for those developing new deconvolution methods and help improve their to better account for the presence of missing cell types. Our results suggest that deconvolution methods should consider the possibility of missing cell types.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"25 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143790192","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}

引用次数: 0