Genome Biology最新文献

Multi-omics approaches reveal that diffuse midline gliomas present altered DNA replication and are susceptible to replication stress therapy

IF 12.3 1区生物学

Genome Biology Pub Date : 2024-12-20 DOI: 10.1186/s13059-024-03460-y

Anastasia E. Hains, Kashish Chetal, Tsunetoshi Nakatani, Joana G. Marques, Andreas Ettinger, Carlos A. O. Biagi Junior, Adriana Gonzalez-Sandoval, Renjitha Pillai, Mariella G. Filbin, Maria-Elena Torres-Padilla, Ruslan I. Sadreyev, Capucine Van Rechem

{"title":"Multi-omics approaches reveal that diffuse midline gliomas present altered DNA replication and are susceptible to replication stress therapy","authors":"Anastasia E. Hains, Kashish Chetal, Tsunetoshi Nakatani, Joana G. Marques, Andreas Ettinger, Carlos A. O. Biagi Junior, Adriana Gonzalez-Sandoval, Renjitha Pillai, Mariella G. Filbin, Maria-Elena Torres-Padilla, Ruslan I. Sadreyev, Capucine Van Rechem","doi":"10.1186/s13059-024-03460-y","DOIUrl":"https://doi.org/10.1186/s13059-024-03460-y","url":null,"abstract":"The fatal diffuse midline gliomas (DMG) are characterized by an undruggable H3K27M mutation in H3.1 or H3.3. K27M impairs normal development by stalling differentiation. The identification of targetable pathways remains very poorly explored. Toward this goal, we undertake a multi-omics approach to evaluate replication timing profiles, transcriptomics, and cell cycle features in DMG cells from both H3.1K27M and H3.3K27M subgroups and perform a comparative, integrative data analysis with healthy brain tissue. DMG cells present differential replication timing in each subgroup, which, in turn, correlates with significant differential gene expression. Differentially expressed genes in S phase are involved in various pathways related to DNA replication. We detect increased expression of DNA replication genes earlier in the cell cycle in DMG cell lines compared to normal brain cells. Furthermore, the distance between origins of replication in DMG cells is smaller than in normal brain cells and their fork speed is slower, a read-out of replication stress. Consistent with these findings, DMG tumors present high replication stress signatures in comparison to normal brain cells. Finally, DMG cells are specifically sensitive to replication stress therapy. This whole genome multi-omics approach provides insights into the cell cycle regulation of DMG via the H3K27M mutations and establishes a pharmacologic vulnerability in DNA replication, which resolves a potentially novel therapeutic strategy for this non-curable disease.\u0000","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"20 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142858388","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

Systematic evaluation of methylation-based cell type deconvolution methods for plasma cell-free DNA

IF 12.3 1区生物学

Genome Biology Pub Date : 2024-12-19 DOI: 10.1186/s13059-024-03456-8

Tongyue Sun, Jinqi Yuan, Yacheng Zhu, Jingqi Li, Shen Yang, Junpeng Zhou, Xinzhou Ge, Susu Qu, Wei Li, Jingyi Jessica Li, Yumei Li

{"title":"Systematic evaluation of methylation-based cell type deconvolution methods for plasma cell-free DNA","authors":"Tongyue Sun, Jinqi Yuan, Yacheng Zhu, Jingqi Li, Shen Yang, Junpeng Zhou, Xinzhou Ge, Susu Qu, Wei Li, Jingyi Jessica Li, Yumei Li","doi":"10.1186/s13059-024-03456-8","DOIUrl":"https://doi.org/10.1186/s13059-024-03456-8","url":null,"abstract":"Plasma cell-free DNA (cfDNA) is derived from cellular death in various tissues. Investigating the tissue origin of cfDNA through cell type deconvolution, we can detect changes in tissue homeostasis that occur during disease progression or in response to treatment. Consequently, cfDNA has emerged as a valuable noninvasive biomarker for disease detection and treatment monitoring. Although there are many methylation-based methods for cfDNA cell type deconvolution, a comprehensive and systematic evaluation of these methods has yet to be conducted. In this study, we benchmark five methods: MethAtlas, cfNOMe toolkit, CelFiE, CelFEER, and UXM. Utilizing deep whole-genome bisulfite sequencing data from 35 human cell types, we generate in silico cfDNA samples with ground truth cell type proportions to assess the deconvolution performance of the five methods under multiple scenarios. Our findings indicate that multiple factors, including reference marker selection, sequencing depth, and reference atlas completeness, jointly influence the deconvolution performance. Notably, an incomplete reference with missing markers or cell types leads to suboptimal results. We observe performance differences among methods under varying conditions, underscoring the importance of tailoring cfDNA deconvolution analyses. To increase the clinical relevance of our findings, we further evaluate each method’s performance in potential clinical applications using real-world datasets. Based on the benchmark results, we propose general guidelines to choose the suitable methods based on sequencing depth of the cfDNA data and completeness of the reference atlas to maximize the performance of methylation-based cfDNA cell type deconvolution.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"87 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142849135","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

TEMPTED: time-informed dimensionality reduction for longitudinal microbiome studies

IF 12.3 1区生物学

Genome Biology Pub Date : 2024-12-19 DOI: 10.1186/s13059-024-03453-x

Pixu Shi, Cameron Martino, Rungang Han, Stefan Janssen, Gregory Buck, Myrna Serrano, Kouros Owzar, Rob Knight, Liat Shenhav, Anru R. Zhang

引用次数: 0

Transcriptional regulatory network reveals key transcription factors for regulating agronomic traits in soybean

IF 12.3 1区生物学

Genome Biology Pub Date : 2024-12-18 DOI: 10.1186/s13059-024-03454-w

Wu Jiao, Mangmang Wang, Yijian Guan, Wei Guo, Chang Zhang, Yuanchun Wei, Zhenwei Zhao, Hongyu Ma, Longfei Wang, Xinyu Jiang, Wenxue Ye, Dong Cao, Qingxin Song

{"title":"Transcriptional regulatory network reveals key transcription factors for regulating agronomic traits in soybean","authors":"Wu Jiao, Mangmang Wang, Yijian Guan, Wei Guo, Chang Zhang, Yuanchun Wei, Zhenwei Zhao, Hongyu Ma, Longfei Wang, Xinyu Jiang, Wenxue Ye, Dong Cao, Qingxin Song","doi":"10.1186/s13059-024-03454-w","DOIUrl":"https://doi.org/10.1186/s13059-024-03454-w","url":null,"abstract":"Transcription factors (TFs) bind regulatory genomic regions to orchestrate spatio-temporal expression of target genes. Global dissection of the cistrome is critical for elucidating transcriptional networks underlying complex agronomic traits in crops. Here, we generate a comprehensive genome-wide binding map for 148 TFs using DNA affinity purification sequencing in soybean. We find TF binding sites (TFBSs) exhibit elevated chromatin accessibility and contain more rare alleles than other genomic regions. Intriguingly, the methylation variations at TFBSs partially contribute to expression bias among whole genome duplication paralogs. Furthermore, we construct a soybean gene regulatory network (SoyGRN) by integrating TF-target interactions with diverse datasets encompassing gene expression, TFBS motifs, chromatin accessibility, and evolutionarily conserved regulation. SoyGRN comprises 2.44 million genome-wide interactions among 3188 TFs and 51,665 target genes. We successfully identify key TFs governing seed coat color and oil content and prioritize candidate genes within quantitative trait loci associated with various agronomic traits using SoyGRN. To accelerate utilization of SoyGRN, we develop an interactive webserver ( www.soytfbase.cn ) for soybean community to explore functional TFs involved in trait regulation. Overall, our study unravels intricate landscape of TF-target interactions in soybean and provides a valuable resource for dissecting key regulators for control of agronomic traits to accelerate soybean improvement.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"1 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142849130","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

HIPSD&R-seq enables scalable genomic copy number and transcriptome profiling

IF 12.3 1区生物学

Genome Biology Pub Date : 2024-12-18 DOI: 10.1186/s13059-024-03450-0

Jan Otoničar, Olga Lazareva, Jan-Philipp Mallm, Milena Simovic-Lorenz, George Philippos, Pooja Sant, Urja Parekh, Linda Hammann, Albert Li, Umut Yildiz, Mikael Marttinen, Judith Zaugg, Kyung Min Noh, Oliver Stegle, Aurélie Ernst

引用次数: 0

Cas12f1 gene drives propagate efficiently in herpesviruses and induce minimal resistance

IF 12.3 1区生物学

Genome Biology Pub Date : 2024-12-18 DOI: 10.1186/s13059-024-03455-9

Zhuangjie Lin, Qiaorui Yao, Keyuan Lai, Kehua Jiao, Xianying Zeng, Guanxiong Lei, Tongwen Zhang, Hongsheng Dai

{"title":"Cas12f1 gene drives propagate efficiently in herpesviruses and induce minimal resistance","authors":"Zhuangjie Lin, Qiaorui Yao, Keyuan Lai, Kehua Jiao, Xianying Zeng, Guanxiong Lei, Tongwen Zhang, Hongsheng Dai","doi":"10.1186/s13059-024-03455-9","DOIUrl":"https://doi.org/10.1186/s13059-024-03455-9","url":null,"abstract":"Synthetic CRISPR-Cas9 gene drive has been developed to control harmful species. However, resistance to Cas9 gene drive can be acquired easily when DNA repair mechanisms patch up the genetic insults introduced by Cas9 and incorporate mutations to the sgRNA target. Although many strategies to reduce the occurrence of resistance have been developed so far, they are difficult to implement and not always effective. Here, Cas12f1, a recently developed CRISPR-Cas system with minimal potential for causing mutations within target sequences, has been explored as a potential platform for yielding low-resistance in gene drives. We construct Cas9 and Cas12f1 gene drives in a fast-replicating DNA virus, HSV1. Cas9 and Cas12f1 gene drives are able to spread among the HSV1 population with specificity towards their target sites, and their transmission among HSV1 viruses is not significantly affected by the reduced fitness incurred by the viral carriers. Cas12f1 gene drives spread similarly as Cas9 gene drives at high introduction frequency but transmit more slowly than Cas9 gene drives at low introduction frequency. However, Cas12f1 gene drives outperform Cas9 gene drives because they reach higher penetration and induce lower resistance than Cas9 gene drives in all cases. Due to lower resistance and higher penetration, Cas12f1 gene drives could potentially supplant Cas9 gene drives for population control.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"80 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142849132","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

GenomeDelta: detecting recent transposable element invasions without repeat library

IF 12.3 1区生物学

Genome Biology Pub Date : 2024-12-18 DOI: 10.1186/s13059-024-03459-5

Riccardo Pianezza, Anna Haider, Robert Kofler

引用次数: 0

Evaluating data requirements for high-quality haplotype-resolved genomes for creating robust pangenome references

IF 12.3 1区生物学

Genome Biology Pub Date : 2024-12-18 DOI: 10.1186/s13059-024-03452-y

Prasad Sarashetti, Josipa Lipovac, Filip Tomas, Mile Šikić, Jianjun Liu

{"title":"Evaluating data requirements for high-quality haplotype-resolved genomes for creating robust pangenome references","authors":"Prasad Sarashetti, Josipa Lipovac, Filip Tomas, Mile Šikić, Jianjun Liu","doi":"10.1186/s13059-024-03452-y","DOIUrl":"https://doi.org/10.1186/s13059-024-03452-y","url":null,"abstract":"Long-read technologies from Pacific Biosciences (PacBio) and Oxford Nanopore Technologies (ONT) have transformed genomics research by providing diverse data types like HiFi, Duplex, and ultra-long ONT. Despite recent strides in achieving haplotype-phased gapless genome assemblies using long-read technologies, concerns persist regarding the representation of genetic diversity, prompting the development of pangenome references. However, pangenome studies face challenges related to data types, volumes, and cost considerations for each assembled genome, while striving to maintain sensitivity. The absence of comprehensive guidance on optimal data selection exacerbates these challenges. Our study evaluates recommended data types and volumes required to establish a robust de novo genome assembly pipeline for population-level pangenome projects, extensively examining performance between ONT’s Duplex and PacBio HiFi datasets in the context of achieving high-quality phased genomes with enhanced contiguity and completeness. The results show that achieving chromosome-level haplotype-resolved assembly requires 20 × high-quality long reads such as PacBio HiFi or ONT Duplex, combined with 15–20 × of ultra-long ONT per haplotype and 10 × of long-range data such as Omni-C or Hi-C. High-quality long reads from both platforms yield assemblies with comparable contiguity, with HiFi excelling in phasing accuracies, while Duplex generates more T2T contigs. Our study provides insights into optimal data types and volumes for robust de novo genome assembly in population-level pangenome projects. Reassessing the recommended data types and volumes in this study and aligning them with practical economic limitations are vital to the pangenome research community, contributing to their efforts and pushing genomic studies with broader impacts.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"1 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142849131","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

SyntheVAEiser: augmenting traditional machine learning methods with VAE-based gene expression sample generation for improved cancer subtype predictions SyntheVAEiser：利用基于 VAE 的基因表达样本生成增强传统机器学习方法，改进癌症亚型预测

IF 12.3 1区生物学

Genome Biology Pub Date : 2024-12-18 DOI: 10.1186/s13059-024-03431-3

Brian Karlberg, Raphael Kirchgaessner, Jordan Lee, Matthew Peterkort, Liam Beckman, Jeremy Goecks, Kyle Ellrott

引用次数: 0

EpiGePT: a pretrained transformer-based language model for context-specific human epigenomics

IF 12.3 1区生物学

Genome Biology Pub Date : 2024-12-18 DOI: 10.1186/s13059-024-03449-7

Zijing Gao, Qiao Liu, Wanwen Zeng, Rui Jiang, Wing Hung Wong

引用次数: 0