Genome research最新文献

Diffusion-based generation of gene regulatory networks from scRNA-seq data with DigNet. 利用DigNet从scRNA-seq数据中扩散生成基因调控网络。

IF 6.2 2区生物学

Genome research Pub Date : 2025-02-14 DOI: 10.1101/gr.279551.124

Chuanyuan Wang, Zhi-Ping Liu

{"title":"Diffusion-based generation of gene regulatory networks from scRNA-seq data with DigNet.","authors":"Chuanyuan Wang, Zhi-Ping Liu","doi":"10.1101/gr.279551.124","DOIUrl":"10.1101/gr.279551.124","url":null,"abstract":"A gene regulatory network (GRN) intricately encodes the interconnectedness of identities and functionalities of genes within cells, ultimately shaping cellular specificity. Despite decades of endeavors, reverse engineering of GRNs from gene expression profiling data remains a profound challenge, particularly when it comes to reconstructing cell-specific GRNs that are tailored to precise cellular and genetic contexts. Here, we propose a discrete diffusion generation model, called DigNet, capable of generating corresponding GRNs from high-throughput single-cell RNA sequencing (scRNA-seq) data. DigNet embeds the network generation process into a multistep recovery procedure with Markov properties. Each intermediate step has a specific model to recover a portion of the gene regulatory architectures. It thus can ensure compatibility between global network structures and regulatory modules through the unique multistep diffusion procedure. Furthermore, through iMetacell integration and non-Euclidean discrete space modeling, DigNet is robust to the presence of noise in scRNA-seq data and the sparsity of GRNs. Benchmark evaluation results against more than a dozen state-of-the-art network inference methods demonstrate that DigNet achieves superior performance across various single-cell GRN reconstruction experiments. Furthermore, DigNet provides unique insights into the immune response in breast cancer, derived from differential gene regulation identified in T cells. As an open-source software, DigNet offers a powerful and effective tool for generating cell-specific GRNs from scRNA-seq data.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":" ","pages":"340-354"},"PeriodicalIF":6.2,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Fast sequence alignment for centromere with RaMA

IF 7 2区生物学

Genome research Pub Date : 2025-02-12 DOI: 10.1101/gr.279763.124

Pinglu Zhang, Yanming Wei, Qinzhong Tian, Quan Zou, Yansu Wang

引用次数: 0

The role of transposon activity in shaping cis-regulatory element evolution after whole genome duplication

IF 7 2区生物学

Genome research Pub Date : 2025-02-12 DOI: 10.1101/gr.278931.124

Oystein Monsen, Lars Gronvold, Alex Datsomor, Thomas Nelson Harvey, James Kijas, Alexander Sang-Jae Suh, Torgeir Rhoden Hvidsten, Simen Rod Sandve

{"title":"The role of transposon activity in shaping cis-regulatory element evolution after whole genome duplication","authors":"Oystein Monsen, Lars Gronvold, Alex Datsomor, Thomas Nelson Harvey, James Kijas, Alexander Sang-Jae Suh, Torgeir Rhoden Hvidsten, Simen Rod Sandve","doi":"10.1101/gr.278931.124","DOIUrl":"https://doi.org/10.1101/gr.278931.124","url":null,"abstract":"Whole-genome duplications (WGD) and transposable element (TE) activity can act synergistically in genome evolution. WGDs can increase TE activity directly through cellular stress or indirectly by relaxing selection against TE insertions in functionally redundant, duplicated regions. Because TEs can function as, or evolve into, TE-derived cis-regulatory elements (TE-CREs), bursts of TE activity following WGD are therefore likely to impact evolution of gene regulation. Yet, the role of TEs in genome regulatory evolution after WGDs is not well understood. Here we used Atlantic salmon as a model system to explore how TE activity after the salmonid WGD ~100MYA shaped CRE evolution. We identified 55,080 putative TE-CREs using chromatin accessibility data from liver and brain. Retroelements were both the dominant source of TE-CREs and had higher regulatory activity in MPRA experiments compared to DNA elements. A minority of TE-subfamilies (16%) accounted for 46% of TE-CREs, but these \"CRE-superspreaders\" were mostly active prior to the WGD. Analysis of individual TE insertions, however, revealed enrichment of TE-CREs originating from WGD-associated TE activity, particularly for the DTT (Tc1-Mariner) DNA elements. Furthermore, coexpression analyses supported the presence of TE-driven gene regulatory network evolution, including DTT elements active at the time of WGD. In conclusion, our study supports a scenario where TE activity has been important in genome regulatory evolution, either through relaxed selective constraints, or strong selection to recalibrate optimal gene expression phenotypes, during a transient period following genome doubling.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"9 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143401580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Variation in the fitness impact of translationally optimal codons among animals

IF 7 2区生物学

Genome research Pub Date : 2025-02-10 DOI: 10.1101/gr.279837.124

Florian Bénitière, Tristan Lefébure, Laurent Duret

{"title":"Variation in the fitness impact of translationally optimal codons among animals","authors":"Florian Bénitière, Tristan Lefébure, Laurent Duret","doi":"10.1101/gr.279837.124","DOIUrl":"https://doi.org/10.1101/gr.279837.124","url":null,"abstract":"Early studies in invertebrate model organisms (fruit flies, nematodes) showed that their synonymous codon usage is under selective pressure to optimize translation efficiency in highly expressed genes (a process called translational selection). In contrast, mammals show little evidence of selection for translationally optimal codons. To understand this difference, we examined the use of synonymous codons in 223 metazoan species, covering a wide range of animal clades. For each species, we predicted the set of optimal codons based on the pool of tRNA genes present in its genome, and we analyzed how the frequency of optimal codons correlates with gene expression to quantify the intensity of translational selection (S). We observed that few metazoans show clear signs of translational selection. As predicted by the nearly neutral theory, the highest values of S are observed in species with large effective population sizes (Ne). Overall, however, Ne appears to be a poor predictor of the intensity of translational selection, suggesting important differences in the fitness effect of synonymous codon usage across taxa. We propose that the few animal taxa that are clearly affected by translational selection correspond to organisms with strong constraints for a very rapid growth rate.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"9 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143385075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Nucleosome-binding by TP53, TP63, and TP73 is determined by the composition, accessibility, and helical orientation of their binding sites

IF 7 2区生物学

Genome research Pub Date : 2025-02-10 DOI: 10.1101/gr.279541.124

Patrick Wilson, Xinyang Yu, Christopher R Handelmann, Michael J Buck

{"title":"Nucleosome-binding by TP53, TP63, and TP73 is determined by the composition, accessibility, and helical orientation of their binding sites","authors":"Patrick Wilson, Xinyang Yu, Christopher R Handelmann, Michael J Buck","doi":"10.1101/gr.279541.124","DOIUrl":"https://doi.org/10.1101/gr.279541.124","url":null,"abstract":"The TP53 family of transcription factors plays key roles in driving development and combating cancer by regulating gene expression. TP53, TP63, and TP73 - the three members of the TP53 family - regulate gene expression by binding to their DNA binding sites, many of which are situated within nucleosomes. To thoroughly examine the nucleosome-binding abilities of the TP53 family, we used Pioneer-seq, a technique that assesses a transcription factor's binding affinity to its DNA binding sites at all possible positions within the nucleosome core particle. Using Pioneer-seq, we analyzed the binding affinity of TP53, TP63, and TP73 to 10 TP53-family binding sites across the nucleosome core particle. We found that the affinity of TP53, TP63, and TP73 for nucleosomes was primarily determined by the positioning of TP53-family binding sites within nucleosomes; TP53-family members bind strongly to the more accessible edges of nucleosomes but weakly to the less accessible centers of nucleosomes. Our results further show that the DNA-helical orientation of TP53-family binding sites within nucleosomal DNA impacts the nucleosome-binding affinity of TP53-family members, with binding site composition impacting each TP53-family member's affinity only when the binding site location was accessible. Taken together, our results show that the accessibility, composition, and helical orientation of TP53-family binding sites collectively determine the nucleosome-binding affinities of TP53, TP63, and TP73. These findings help explain the rules underlying TP53-family-nucleosome binding and thus provide requisite insight into how we may better control gene-expression changes involved in development and tumor suppression.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"60 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143385078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Kernel-bounded clustering for spatial transcriptomics enables scalable discovery of complex spatial domains

IF 7 2区生物学

Genome research Pub Date : 2025-02-05 DOI: 10.1101/gr.278983.124

Hang Zhang, Yi Zhang, Kai Ming Ting, Jie Zhang, Qiuran Zhao

{"title":"Kernel-bounded clustering for spatial transcriptomics enables scalable discovery of complex spatial domains","authors":"Hang Zhang, Yi Zhang, Kai Ming Ting, Jie Zhang, Qiuran Zhao","doi":"10.1101/gr.278983.124","DOIUrl":"https://doi.org/10.1101/gr.278983.124","url":null,"abstract":"Spatial transcriptomics are a collection of technologies that have enabled characterization of gene expression profiles and spatial information in tissue samples. Existing methods for clustering spatial transcriptomics data have primarily focused on data transformation techniques to represent the data suitably for subsequent clustering analysis, often using an existing clustering algorithm. These methods have limitations in handling complex data characteristics with varying densities, sizes, and shapes (in the transformed space on which clustering is performed), and they have high computational complexity, resulting in unsatisfactory clustering outcomes and slow execution time even with GPUs. Rather than focusing on data transformation techniques, we propose a new clustering algorithm called kernel-bounded clustering (KBC). It has two unique features: (1) It is the first clustering algorithm that employs a distributional kernel to recruit members of a cluster, enabling clusters of varying densities, sizes, and shapes to be discovered, and (2) it is a linear-time clustering algorithm that significantly enhances the speed of clustering analysis, enabling researchers to effectively handle large-scale spatial transcriptomics data sets. We show that (1) KBC works well with a simple data transformation technique called the Weisfeiler–Lehman scheme, and (2) a combination of KBC and the Weisfeiler–Lehman scheme produces good clustering outcomes, and it is faster and easier-to-use than many methods that employ existing clustering algorithms and data transformation techniques.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"40 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143192103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The additional diagnostic yield of long-read sequencing in undiagnosed rare diseases

IF 7 2区生物学

Genome research Pub Date : 2025-02-03 DOI: 10.1101/gr.279970.124

Giulia F. Del Gobbo, Kym M. Boycott

{"title":"The additional diagnostic yield of long-read sequencing in undiagnosed rare diseases","authors":"Giulia F. Del Gobbo, Kym M. Boycott","doi":"10.1101/gr.279970.124","DOIUrl":"https://doi.org/10.1101/gr.279970.124","url":null,"abstract":"Long-read sequencing (LRS) is a promising technology positioned to study the significant proportion of rare diseases (RDs) that remain undiagnosed as it addresses many of the limitations of short-read sequencing, detecting and clarifying additional disease-associated variants that may be missed by the current standard diagnostic workflow for RDs. Some key areas where additional diagnostic yields may be realized include: (1) detection and resolution of structural variants (SVs); (2) detection and characterization of tandem repeat expansions; (3) coverage of regions of high sequence similarity; (4) variant phasing; (5) the use of de novo genome assemblies for reference-based or graph genome variant detection; and (6) epigenetic and transcriptomic evaluations. Examples from over 50 studies support that the main areas of added diagnostic yield currently lie in SV detection and characterization, repeat expansion assessment, and phasing (with or without DNA methylation information). Several emerging studies applying LRS in cohorts of undiagnosed RDs also demonstrate that LRS can boost diagnostic yields following negative standard-of-care clinical testing and provide an added yield of 7%–17% following negative short-read genome sequencing. With this evidence of improved diagnostic yield, we discuss the incorporation of LRS into the diagnostic care pathway for undiagnosed RDs, including current challenges and considerations, with the ultimate goal of ending the diagnostic odyssey for countless individuals with RDs.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"35 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143077627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

k-mer approaches for biodiversity genomics

IF 7 2区生物学

Genome research Pub Date : 2025-01-31 DOI: 10.1101/gr.279452.124

Katharine M. Jenike, Lucía Campos-Domínguez, Marilou Boddé, José Cerca, Christina N. Hodson, Michael C. Schatz, Kamil S. Jaron

{"title":"k-mer approaches for biodiversity genomics","authors":"Katharine M. Jenike, Lucía Campos-Domínguez, Marilou Boddé, José Cerca, Christina N. Hodson, Michael C. Schatz, Kamil S. Jaron","doi":"10.1101/gr.279452.124","DOIUrl":"https://doi.org/10.1101/gr.279452.124","url":null,"abstract":"The wide array of currently available genomes displays a wonderful diversity in size, composition, and structure and is quickly expanding thanks to several global biodiversity genomics initiatives. However, sequencing of genomes, even with the latest technologies, can still be challenging for both technical (e.g., small physical size, contaminated samples, or access to appropriate sequencing platforms) and biological reasons (e.g., germline-restricted DNA, variable ploidy levels, sex chromosomes, or very large genomes). In recent years, k-mer-based techniques have become popular to overcome some of these challenges. They are based on the simple process of dividing the analyzed sequences (e.g., raw reads or genomes) into a set of subsequences of length k, called k-mers, and then analyzing the frequency or sequences of those k-mers. Analyses based on k-mers allow for a rapid and intuitive assessment of complex sequencing data sets. Here, we provide a comprehensive review to the theoretical properties and practical applications of k-mers in biodiversity genomics with a special focus on genome modeling.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"15 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143072635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Enhancing nanopore adaptive sampling for PromethION using readfish at scale

IF 7 2区生物学

Genome research Pub Date : 2025-01-30 DOI: 10.1101/gr.279329.124

Rory Munro, Alex Payne, Nadine Holmes, Chris Moore, Inswasti Cahyani, Matt Loose

引用次数: 0

Rapid and accurate demultiplexing of direct RNA nanopore sequencing datasets with SeqTagger

IF 7 2区生物学

Genome research Pub Date : 2025-01-29 DOI: 10.1101/gr.279290.124

Leszek P Pryszcz, Gregor Diensthuber, Laia Llovera, Rebeca Medina, Anna Delgado-Tejedor, Luca Cozzuto, Julia Ponomarenko, Eva Maria Novoa

{"title":"Rapid and accurate demultiplexing of direct RNA nanopore sequencing datasets with SeqTagger","authors":"Leszek P Pryszcz, Gregor Diensthuber, Laia Llovera, Rebeca Medina, Anna Delgado-Tejedor, Luca Cozzuto, Julia Ponomarenko, Eva Maria Novoa","doi":"10.1101/gr.279290.124","DOIUrl":"https://doi.org/10.1101/gr.279290.124","url":null,"abstract":"Nanopore direct RNA sequencing (DRS) enables direct measurement of RNA molecules, including their native RNA modifications, without prior conversion to cDNA. However, commercial methods for molecular barcoding of multiple DRS samples are lacking, and community-driven efforts, such as DeePlexiCon, are not compatible with newer RNA chemistry flowcells and the latest-generation GPU cards. To overcome these limitations, we introduce SeqTagger, a rapid and robust method that can demultiplex direct RNA sequencing datasets with 99% precision and 95% recall. We demonstrate the applicability of SeqTagger in both RNA002/R9.4 and RNA004/RNA chemistries and show its robust performance both for long and short RNA libraries, including custom libraries that do not contain standard poly(A) tails, such as Nano-tRNAseq libraries. Finally, we demonstrate that increasing the multiplexing up to 96 barcodes yields highly accurate demultiplexing models. SeqTagger can be executed in a standalone manner or through the MasterOfPores NextFlow workflow. The availability of an efficient and simple multiplexing strategy improves the cost-effectiveness of this technology and facilitates the analysis of low-input biological samples.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"29 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143056331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0