Genome Biology最新文献

{"title":"TEMPTED: time-informed dimensionality reduction for longitudinal microbiome studies","authors":"Pixu Shi, Cameron Martino, Rungang Han, Stefan Janssen, Gregory Buck, Myrna Serrano, Kouros Owzar, Rob Knight, Liat Shenhav, Anru R. Zhang","doi":"10.1186/s13059-024-03453-x","DOIUrl":"https://doi.org/10.1186/s13059-024-03453-x","url":null,"abstract":"Longitudinal studies are crucial for understanding complex microbiome dynamics and their link to health. We introduce TEMPoral TEnsor Decomposition (TEMPTED), a time-informed dimensionality reduction method for high-dimensional longitudinal data that treats time as a continuous variable, effectively characterizing temporal information and handling varying temporal sampling. TEMPTED captures key microbial dynamics, facilitates beta-diversity analysis, and enhances reproducibility by transferring learned representations to new data. In simulations, it achieves 90% accuracy in phenotype classification, significantly outperforming existing methods. In real data, TEMPTED identifies vaginal microbial markers linked to term and preterm births, demonstrating robust performance across datasets and sequencing platforms.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"114 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142849043","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}

{"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}

{"title":"HIPSD&R-seq enables scalable genomic copy number and transcriptome profiling","authors":"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","doi":"10.1186/s13059-024-03450-0","DOIUrl":"https://doi.org/10.1186/s13059-024-03450-0","url":null,"abstract":"Single-cell DNA sequencing (scDNA-seq) enables decoding somatic cancer variation. Existing methods are hampered by low throughput or cannot be combined with transcriptome sequencing in the same cell. We propose HIPSD&R-seq (HIgh-throughPut Single-cell Dna and Rna-seq), a scalable yet simple and accessible assay to profile low-coverage DNA and RNA in thousands of cells in parallel. Our approach builds on a modification of the 10X Genomics platform for scATAC and multiome profiling. In applications to human cell models and primary tissue, we demonstrate the feasibility to detect rare clones and we combine the assay with combinatorial indexing to profile over 17,000 cells.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"64 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142849044","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}

{"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}

{"title":"GenomeDelta: detecting recent transposable element invasions without repeat library","authors":"Riccardo Pianezza, Anna Haider, Robert Kofler","doi":"10.1186/s13059-024-03459-5","DOIUrl":"https://doi.org/10.1186/s13059-024-03459-5","url":null,"abstract":"We present GenomeDelta, a novel tool for identifying sample-specific sequences, such as recent transposable element (TE) invasions, without requiring a repeat library. GenomeDelta compares high-quality assemblies with short-read data to detect sequences absent from the short reads. It is applicable to both model and non-model organisms and can identify recent TE invasions, spatially heterogeneous sequences, viral insertions, and hotizontal gene transfers. GenomeDelta was validated with simulated and real data and used to discover three recent TE invasions in Drosophila melanogaster and a novel TE with geographic variation in Zymoseptoria tritici.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"22 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142849045","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}

{"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}

{"title":"SyntheVAEiser: augmenting traditional machine learning methods with VAE-based gene expression sample generation for improved cancer subtype predictions","authors":"Brian Karlberg, Raphael Kirchgaessner, Jordan Lee, Matthew Peterkort, Liam Beckman, Jeremy Goecks, Kyle Ellrott","doi":"10.1186/s13059-024-03431-3","DOIUrl":"https://doi.org/10.1186/s13059-024-03431-3","url":null,"abstract":"The accuracy of machine learning methods is often limited by the amount of training data that is available. We proposed to improve machine learning training regimes by augmenting datasets with synthetically generated samples. We present a method for synthesizing gene expression samples and test the system’s capabilities for improving the accuracy of categorical prediction of cancer subtypes. We developed SyntheVAEiser, a variational autoencoder based tool that was trained and tested on over 8000 cancer samples. We have shown that this technique can be used to augment machine learning tasks and increase performance of recognition of underrepresented cohorts.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"23 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142849136","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}

{"title":"EpiGePT: a pretrained transformer-based language model for context-specific human epigenomics","authors":"Zijing Gao, Qiao Liu, Wanwen Zeng, Rui Jiang, Wing Hung Wong","doi":"10.1186/s13059-024-03449-7","DOIUrl":"https://doi.org/10.1186/s13059-024-03449-7","url":null,"abstract":"The inherent similarities between natural language and biological sequences have inspired the use of large language models in genomics, but current models struggle to incorporate chromatin interactions or predict in unseen cellular contexts. To address this, we propose EpiGePT, a transformer-based model designed for predicting context-specific human epigenomic signals. By incorporating transcription factor activities and 3D genome interactions, EpiGePT outperforms existing methods in epigenomic signal prediction tasks, especially in cell-type-specific long-range interaction predictions and genetic variant impacts, advancing our understanding of gene regulation. A free online prediction service is available at http://health.tsinghua.edu.cn/epigept .","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"38 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142849133","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}

{"title":"SQUiD: ultra-secure storage and analysis of genetic data for the advancement of precision medicine","authors":"Jacob Blindenbach, Jiayi Kang, Seungwan Hong, Caline Karam, Thomas Lehner, Gamze Gürsoy","doi":"10.1186/s13059-024-03447-9","DOIUrl":"https://doi.org/10.1186/s13059-024-03447-9","url":null,"abstract":"Cloud computing allows storing the ever-growing genotype-phenotype datasets crucial for precision medicine. Due to the sensitive nature of this data and varied laws and regulations, additional security measures are needed to ensure data privacy. We develop SQUiD, a secure queryable database for storing and analyzing genotype-phenotype data. SQUiD allows storage and secure querying of data in a low-security, low-cost public cloud using homomorphic encryption in a multi-client setting. We demonstrate SQUiD’s practical usability and scalability using synthetic and UK Biobank data.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"58 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142849046","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}

{"title":"Increased spatial coupling of integrin and collagen IV in the immunoresistant clear-cell renal-cell carcinoma tumor microenvironment","authors":"Alex C. Soupir, Mitchell T. Hayes, Taylor C. Peak, Oscar Ospina, Nicholas H. Chakiryan, Anders E. Berglund, Paul A. Stewart, Jonathan Nguyen, Carlos Moran Segura, Natasha L. Francis, Paola M. Ramos Echevarria, Jad Chahoud, Roger Li, Kenneth Y. Tsai, Jodi A. Balasi, Yamila Caraballo Peres, Jasreman Dhillon, Lindsey A. Martinez, Warren E. Gloria, Nathan Schurman, Sean Kim, Mark Gregory, James Mulé, Brooke L. Fridley, Brandon J. Manley","doi":"10.1186/s13059-024-03435-z","DOIUrl":"https://doi.org/10.1186/s13059-024-03435-z","url":null,"abstract":"Immunotherapy has improved survival for patients with advanced clear cell renal cell carcinoma (ccRCC), but resistance to therapy develops in most patients. We use cellular-resolution spatial transcriptomics in patients with immunotherapy naïve and exposed primary ccRCC tumors to better understand immunotherapy resistance. Spatial molecular imaging of tumor and adjacent stroma samples from 21 tumors suggests that viable tumors following immunotherapy harbor more stromal CD8 + T cells and neutrophils than immunotherapy naïve tumors. YES1 is significantly upregulated in immunotherapy exposed tumor cells. Spatial GSEA shows that the epithelial-mesenchymal transition pathway is spatially enriched and the associated ligand-receptor transcript pair COL4A1-ITGAV has significantly higher autocorrelation in the stroma after exposure to immunotherapy. More integrin αV + cells are observed in immunotherapy exposed stroma on multiplex immunofluorescence validation. Compared to other cancers in TCGA, ccRCC tumors have the highest expression of both COL4A1 and ITGAV. Assessing bulk RNA expression and proteomic correlates in CPTAC databases reveals that collagen IV protein is more abundant in advanced stages of disease. Spatial transcriptomics of samples of 3 patient cohorts with cRCC tumors indicates that COL4A1 and ITGAV are more autocorrelated in immunotherapy-exposed stroma compared to immunotherapy-naïve tumors, with high expression among fibroblasts, tumor cells, and endothelium. Further research is needed to understand changes in the ccRCC tumor immune microenvironment and explore potential therapeutic role of integrin after immunotherapy treatment.\u0000","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"53 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142776470","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}