Genome research最新文献_第2页

Nanopore-based consensus sequencing enables accurate multimodal tumor cell-free DNA profiling 基于纳米孔的共识测序能够实现准确的多模态肿瘤无细胞DNA分析

IF 7 2区生物学

Genome research Pub Date : 2025-01-13 DOI: 10.1101/gr.279144.124

Li-Ting Chen, Myrthe Jager, Dàmi Rebergen, Geertruid J. Brink, Tom van den Ende, Willem Vanderlinden, Pauline Kolbeck, Marc Pagès-Gallego, Ymke van der Pol, Nicolle Besselink, Norbert Moldovan, Nizar Hami, Wigard P. Kloosterman, Hanneke van Laarhoven, Florent Mouliere, Ronald Zweemer, Jan Lipfert, Sarah Derks, Alessio Marcozzi, Jeroen de Ridder

{"title":"Nanopore-based consensus sequencing enables accurate multimodal tumor cell-free DNA profiling","authors":"Li-Ting Chen, Myrthe Jager, Dàmi Rebergen, Geertruid J. Brink, Tom van den Ende, Willem Vanderlinden, Pauline Kolbeck, Marc Pagès-Gallego, Ymke van der Pol, Nicolle Besselink, Norbert Moldovan, Nizar Hami, Wigard P. Kloosterman, Hanneke van Laarhoven, Florent Mouliere, Ronald Zweemer, Jan Lipfert, Sarah Derks, Alessio Marcozzi, Jeroen de Ridder","doi":"10.1101/gr.279144.124","DOIUrl":"https://doi.org/10.1101/gr.279144.124","url":null,"abstract":"Shallow genome-wide cell-free DNA (cfDNA) sequencing holds great promise for non-invasive cancer monitoring by providing reliable copy number alteration (CNA) and fragmentomic profiles. Single nucleotide variations (SNVs) are, however, much harder to identify with low sequencing depth due to sequencing errors. Here we present Nanopore Rolling Circle Amplification (RCA)-enhanced Consensus Sequencing (NanoRCS), which leverages RCA and consensus calling based on genome-wide long-read nanopore sequencing to enable simultaneous multimodal tumor fraction estimation through SNVs, CNAs, and fragmentomics. Efficacy of NanoRCS is tested on 18 cancer patient samples and seven healthy controls, demonstrating its ability to reliably detect tumor fractions as low as 0.24%. In vitro experiments confirm that SNV measurements are essential for detecting tumor fractions below 3%. NanoRCS provides the opportunity for cost-effective and rapid processing, which aligns well with clinical needs, particularly in settings where quick and accurate cancer monitoring is essential for personalized treatment strategies.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"83 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142974713","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

Interactive visualization and interpretation of pangenome graphs by linear-reference-based coordinate projection and annotation integration 通过基于线性参照的坐标投影和注释整合，实现庞基因组图谱的交互式可视化和解读

IF 7 2区生物学

Genome research Pub Date : 2025-01-13 DOI: 10.1101/gr.279461.124

Zepu Miao, Jia-Xing Yue

{"title":"Interactive visualization and interpretation of pangenome graphs by linear-reference-based coordinate projection and annotation integration","authors":"Zepu Miao, Jia-Xing Yue","doi":"10.1101/gr.279461.124","DOIUrl":"https://doi.org/10.1101/gr.279461.124","url":null,"abstract":"With the increasing availability of high-quality genome assemblies, pangenome graphs emerged as a new paradigm in the genomics field for identifying, encoding, and presenting genomic variation at both population and species levels. However, it remains challenging to truly dissect and interpret pangenome graphs via biologically informative visualization. To facilitate better exploration and understanding of pangenome graphs towards novel biological insights, here we present a web-based interactive Visualization and interpretation framework for linear-Reference-projected Pangenome Graphs (VRPG). VRPG provides efficient and intuitive supports for exploring and annotating pangenome graphs along a linear-genome-based coordinate system (e.g., that of a primary linear reference genome). Moreover, VRPG offers many unique features such as in-graph path highlighting for graph-constituent input assemblies, copy number characterization for graph-embedding nodes, graph-based mapping for query sequences, all of which are highly valuable for researchers working with pangenome graphs. Additionally, VRPG enables side-by-side visualization between the graph-based pangenome representation and the conventional primary-linear-reference-genome-based feature annotations, therefore seamlessly bridging the graph and linear genomic contexts. To further demonstrate its functionality and scalability, we applied VRPG to the cutting-edge yeast and human reference pangenome graphs derived from hundreds of high-quality genome assemblies via a dedicated web portal and examined their local genome diversity in the graph contexts.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"27 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142974715","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

Single-cell Rapid Capture Hybridization sequencing to reliably detect isoform usage and coding mutations in targeted genes 单细胞快速捕获杂交测序可靠地检测同种异构体的使用和编码突变的目标基因

IF 7 2区生物学

Genome research Pub Date : 2025-01-10 DOI: 10.1101/gr.279322.124

Hongke Peng, Jafar S. Jabbari, Luyi Tian, Changqing Wang, Yupei You, Chong Chyn Chua, Natasha S. Anstee, Noorul Amin, Andrew H. Wei, Nadia Davidson, Andrew W. Roberts, David Huang, Matthew E Ritchie, Rachel Thijssen

{"title":"Single-cell Rapid Capture Hybridization sequencing to reliably detect isoform usage and coding mutations in targeted genes","authors":"Hongke Peng, Jafar S. Jabbari, Luyi Tian, Changqing Wang, Yupei You, Chong Chyn Chua, Natasha S. Anstee, Noorul Amin, Andrew H. Wei, Nadia Davidson, Andrew W. Roberts, David Huang, Matthew E Ritchie, Rachel Thijssen","doi":"10.1101/gr.279322.124","DOIUrl":"https://doi.org/10.1101/gr.279322.124","url":null,"abstract":"Single-cell long-read sequencing has transformed our understanding of isoform usage and the mutation heterogeneity between cells. Despite unbiased in-depth analysis, the low sequencing throughput often results in insufficient read coverage thereby limiting our ability to perform mutation calling for specific genes. Here, we developed a single-cell Rapid Capture Hybridization sequencing (scRaCH-seq) method that demonstrated high specificity and efficiency in capturing targeted transcripts using long-read sequencing, allowing an in-depth analysis of mutation status and transcript usage for genes of interest. The method includes creating a probe panel for transcript capture, using barcoded primers for pooling and efficient sequencing via Oxford Nanopore Technologies platforms. scRaCH-seq is applicable to stored and indexed single-cell cDNA which allows analysis to be combined with existing short-read RNA-seq datasets. In our investigation of BTK and SF3B1 genes in samples from patients with chronic lymphocytic leukaemia (CLL), we detected SF3B1 isoforms and mutations with high sensitivity. Integration with short-read scRNA-seq data revealed significant gene expression differences in SF3B1-mutated CLL cells, though it did not impact the sensitivity of the anti-cancer drug venetoclax. scRaCH-seq's capability to study long-read transcripts of multiple genes makes it a powerful tool for single-cell genomics.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"36 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142961752","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

Proxy panels enable privacy-aware outsourcing of genotype imputation 代理面板使隐私意识外包的基因型插入

IF 7 2区生物学

Genome research Pub Date : 2025-01-10 DOI: 10.1101/gr.278934.124

Degui Zhi, Xiaoqian Jiang, Arif O. Harmanci

{"title":"Proxy panels enable privacy-aware outsourcing of genotype imputation","authors":"Degui Zhi, Xiaoqian Jiang, Arif O. Harmanci","doi":"10.1101/gr.278934.124","DOIUrl":"https://doi.org/10.1101/gr.278934.124","url":null,"abstract":"One of the major challenges in genomic data sharing is protecting participants' privacy in collaborative studies and when genomic data is outsourced to perform analysis tasks, e.g., genotype imputation services and federated collaborations genomic analysis. Although numerous cryptographic methods have been developed, these methods may not yet be practical for population-scale tasks in terms of computational requirements, rely on high-level expertise in security, and require each algorithm to be implemented from scratch. In this study, we focus on outsourcing of genotype imputation, a fundamental task that utilizes population-level reference panels, and develop protocols that rely on using \"proxy-panels\" to protect genotype panels while imputation task is being outsourced at servers. The proxy panels are generated through a series of protection mechanisms such as haplotype sampling, allele hashing, and coordinate anonymization to protect the underlying sensitive panel's genetic variant coordinates, genetic maps, and chromosome-wide haplotypes. While the resulting proxy panels are almost distinct from the sensitive panels, they are valid panels that can be used as input to imputation methods such as Beagle. We demonstrate that proxy-based imputation protects against well-known attacks with a minor decrease in imputation accuracy for variants in a wide range of allele frequencies.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"7 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142961755","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

Post-transcriptional cross- and auto-regulation buffer expression of the human RNA helicases DDX3X and DDX3Y 人RNA解旋酶DDX3X和DDX3Y的转录后交叉和自动调节缓冲表达

IF 7 2区生物学

Genome research Pub Date : 2025-01-10 DOI: 10.1101/gr.279707.124

Shruthi Rengarajan, Jason Derks, Daniel W. Bellott, Nikolai Slavov, David C. Page

{"title":"Post-transcriptional cross- and auto-regulation buffer expression of the human RNA helicases DDX3X and DDX3Y","authors":"Shruthi Rengarajan, Jason Derks, Daniel W. Bellott, Nikolai Slavov, David C. Page","doi":"10.1101/gr.279707.124","DOIUrl":"https://doi.org/10.1101/gr.279707.124","url":null,"abstract":"The Y-linked gene DDX3Y and its X-linked homolog DDX3X survived the evolution of the human sex chromosomes from ordinary autosomes. DDX3X encodes a multifunctional RNA helicase, with mutations causing developmental disorders and cancers. We find that, among X-linked genes with surviving Y homologs, DDX3X is extraordinarily dosage sensitive. Studying cells of individuals with sex chromosome aneuploidy, we observe that when the number of Y Chromosomes increases, DDX3X transcript levels fall; conversely, when the number of X Chromosomes increases, DDX3Y transcript levels fall. In 46,XY cells, CRISPRi knockdown of either DDX3X or DDX3Y causes transcript levels of the homologous gene to rise. In 46,XX cells, chemical inhibition of DDX3X protein activity elicits an increase in DDX3X transcript levels. Thus, perturbation of either DDX3X or DDX3Y expression is buffered: by negative cross-regulation of DDX3X and DDX3Y in 46,XY cells and by negative auto-regulation of DDX3X in 46,XX cells. DDX3X–DDX3Y cross-regulation is mediated through mRNA destabilization—as shown by metabolic labeling of newly transcribed RNA—and buffers total levels of DDX3X and DDX3Y protein in human cells. We infer that post-transcriptional auto-regulation of the ancestral (autosomal) DDX3X gene transmuted into auto- and cross-regulation of DDX3X and DDX3Y as these sex-linked genes evolved from ordinary alleles of their autosomal precursor.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"26 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142961769","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

Timescale and genetic linkage explain the variable impact of defense systems on horizontal gene transfer 时间尺度和遗传连锁解释了防御系统对水平基因转移的可变影响

IF 7 2区生物学

Genome research Pub Date : 2025-01-10 DOI: 10.1101/gr.279300.124

Yang Liu, Joao Botelho, Jaime Iranzo

{"title":"Timescale and genetic linkage explain the variable impact of defense systems on horizontal gene transfer","authors":"Yang Liu, Joao Botelho, Jaime Iranzo","doi":"10.1101/gr.279300.124","DOIUrl":"https://doi.org/10.1101/gr.279300.124","url":null,"abstract":"Prokaryotes have evolved a wide repertoire of defense systems to prevent invasion by mobile genetic elements (MGE). However, because MGE are vehicles for the exchange of beneficial accessory genes, defense systems could consequently impede rapid adaptation in microbial populations. Here, we study how defense systems impact horizontal gene transfer (HGT) in the short and long terms. By combining comparative genomics and phylogeny-aware statistical methods, we quantified the association between the presence of 7 widespread defense systems and the abundance of MGE in the genomes of 196 bacterial and 1 archaeal species. We also calculated the differences in the rates of gene gain and loss between lineages that possess and lack each defense system. Our results show that the impact of defense systems on HGT is highly taxon- and system-dependent, and in most cases not statistically significant. Timescale analysis reveals that defense systems must persist in a lineage for a relatively long time to exert an appreciable negative impact on HGT. In contrast, for shorter evolutionary timescales, frequent co-acquisition of MGE and defense systems results in a net positive association of the latter with HGT. Given the high turnover rates experienced by defense systems, we propose that the inhibitory effect of most defense systems on HGT is masked by their strong linkage with MGE. These findings help explain the contradictory conclusions of previous research by pointing at mobility and within-host retention times as key factors that determine the impact of defense systems on genome plasticity.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"26 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142961756","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

Hierarchical architecture of neo-sex chromosomes and accelerated adaptive evolution in tortricid moths 圆蛾新性染色体的层次结构与加速适应进化

IF 7 2区生物学

Genome research Pub Date : 2025-01-06 DOI: 10.1101/gr.279569.124

Fangyuan Yang, Li-Jun Cao, Petr Nguyen, Zhong-Zheng Ma, Jin-Cui Chen, Wei Song, Shu-Jun Wei

{"title":"Hierarchical architecture of neo-sex chromosomes and accelerated adaptive evolution in tortricid moths","authors":"Fangyuan Yang, Li-Jun Cao, Petr Nguyen, Zhong-Zheng Ma, Jin-Cui Chen, Wei Song, Shu-Jun Wei","doi":"10.1101/gr.279569.124","DOIUrl":"https://doi.org/10.1101/gr.279569.124","url":null,"abstract":"Sex chromosomes can expand through fusion with autosomes, thereby acquiring unique evolutionary patterns. In butterflies and moths (Lepidoptera), these sex chromosome–autosome (SA) fusions occur relatively frequently, suggesting possible evolutionary advantages. Here, we investigated how SA fusion affects chromosome features and molecular evolution in leafroller moths (Lepidoptera: Tortricidae). Phylogenomic analysis showed that Tortricidae diverged ∼124 million years ago, accompanied by an SA fusion between the Merian elements M(20 + 17) and MZ. In contrast to partial autosomal fusions, the fused neo-Z Chromosome developed a hierarchical architecture, in which the three elements exhibit heterogeneous sequence features and evolutionary patterns. Specifically, the M17 part had a distinct base composition and chromatin domains. Unlike M20 and MZ, M17 was expressed at the same levels as autosomes in both sexes, compensating for the lost gene dosage in females. Concurrently, the SA fusion drove M17 as an evolutionary hotspot, accelerating the evolution of several genes related to ecological adaptation (e.g., ABCCs) and facilitating the divergence of closely related species, whereas the undercompensated M20 did not show such an effect. Thus, accelerated evolution under a novel pattern of dosage compensation may have favored the adaptive radiation of this group. This study demonstrates the association between a karyotype variant and adaptive evolution and explains the recurrent SA fusion in the Lepidoptera.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"7 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142935026","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

Fusion, fission, and scrambling of the bilaterian genome in Bryozoa 苔藓虫中双边基因组的融合、裂变和混乱

IF 7 2区生物学

Genome research Pub Date : 2025-01-06 DOI: 10.1101/gr.279636.124

Thomas D. Lewin, Isabel Jiah-Yih Liao, Mu-En Chen, John D.D. Bishop, Peter W.H. Holland, Yi-Jyun Luo

{"title":"Fusion, fission, and scrambling of the bilaterian genome in Bryozoa","authors":"Thomas D. Lewin, Isabel Jiah-Yih Liao, Mu-En Chen, John D.D. Bishop, Peter W.H. Holland, Yi-Jyun Luo","doi":"10.1101/gr.279636.124","DOIUrl":"https://doi.org/10.1101/gr.279636.124","url":null,"abstract":"Groups of orthologous genes are commonly found together on the same chromosome over vast evolutionary distances. This extensive physical gene linkage, known as macrosynteny, is seen between bilaterian phyla as divergent as Chordata, Echinodermata, Mollusca, and Nemertea. Here, we report a unique pattern of genome evolution in Bryozoa, an understudied phylum of colonial invertebrates. Using comparative genomics, we reconstruct the chromosomal evolutionary history of five bryozoans. Multiple ancient chromosome fusions followed by gene mixing led to the near-complete loss of bilaterian linkage groups in the ancestor of extant bryozoans. A second wave of rearrangements, including chromosome fission, then occurred independently in two bryozoan classes, further scrambling bryozoan genomes. We also discover at least five derived chromosomal fusion events shared between bryozoans and brachiopods, supporting the traditional but highly debated Lophophorata hypothesis and suggesting macrosynteny to be a potentially powerful source of phylogenetic information. Finally, we show that genome rearrangements led to the dispersion of genes from bryozoan Hox clusters onto multiple chromosomes. Our findings demonstrate that the canonical bilaterian genome structure has been lost across all studied representatives of an entire phylum, and reveal that linkage group fission can occur very frequently in specific lineages.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"56 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142935025","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

UV damage and repair maps in Drosophila reveal the impact of domain-specific changes in nucleosome repeat length on repair efficiency 果蝇的紫外线损伤和修复图谱揭示了核小体重复长度的区域特异性变化对修复效率的影响

IF 7 2区生物学

Genome research Pub Date : 2025-01-06 DOI: 10.1101/gr.279605.124

Benjamin Morledge-Hampton, Kathiresan Selvam, Manish Chauhan, Alan Goodman, John J. Wyrick

{"title":"UV damage and repair maps in Drosophila reveal the impact of domain-specific changes in nucleosome repeat length on repair efficiency","authors":"Benjamin Morledge-Hampton, Kathiresan Selvam, Manish Chauhan, Alan Goodman, John J. Wyrick","doi":"10.1101/gr.279605.124","DOIUrl":"https://doi.org/10.1101/gr.279605.124","url":null,"abstract":"Cyclobutane pyrimidine dimers (CPDs) are formed in DNA following exposure to ultraviolet (UV) light and are mutagenic unless repaired by nucleotide excision repair (NER). It is known that CPD repair rates vary in different genome regions due to transcription-coupled NER and differences in chromatin accessibility; however, the impact of regional chromatin organization on CPD formation remains unclear. Furthermore, nucleosomes are known to modulate UV damage and repair activity, but how these damage and repair patterns are affected by the overarching chromatin domains in which these nucleosomes are located is not understood. Here, we generated a new CPD damage map in Drosophila S2 cells using CPD-seq and analyzed it alongside existing excision repair-sequencing (XR-seq) data to compare CPD damage formation and repair rates across five previously established chromatin types in Drosophila. This analysis revealed that repair activity varied substantially across different chromatin types, while CPD formation was relatively unaffected. Moreover, we observed distinct patterns of repair activity in nucleosomes located in different chromatin types, which we show is due to domain-specific differences in nucleosome repeat length (NRL). These findings indicate that NRL is altered in different chromatin types in Drosophila and that changes in NRL modulate the repair of UV lesions.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"81 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142934920","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

Identification of the shortest species-specific oligonucleotide sequences 物种特异性最短寡核苷酸序列的鉴定

IF 7 2区生物学

Genome research Pub Date : 2025-01-02 DOI: 10.1101/gr.280070.124

Ioannis Mouratidis, Maxwell Konnaris, Nikol Chantzi, Candace S.Y Chan, Michail Patsakis, Kimonas Provatas, Austin Montgomery, Fotis A. Baltoumas, Congzhou M. Sha, Manvita Mareboina, Georgios A. Pavlopoulos, Dionysios V. Chartoumpekis, Ilias Georgakopoulos-Soares

{"title":"Identification of the shortest species-specific oligonucleotide sequences","authors":"Ioannis Mouratidis, Maxwell Konnaris, Nikol Chantzi, Candace S.Y Chan, Michail Patsakis, Kimonas Provatas, Austin Montgomery, Fotis A. Baltoumas, Congzhou M. Sha, Manvita Mareboina, Georgios A. Pavlopoulos, Dionysios V. Chartoumpekis, Ilias Georgakopoulos-Soares","doi":"10.1101/gr.280070.124","DOIUrl":"https://doi.org/10.1101/gr.280070.124","url":null,"abstract":"Despite the exponential increase in sequencing information driven by massively parallel DNA sequencing technologies, universal and succinct genomic fingerprints for each organism are still missing. Identifying the shortest species-specific nucleic sequences offers insights into species evolution and holds potential practical applications in agriculture, wildlife conservation, and healthcare. We propose a new method for sequence analysis termed nucleic \"quasi-primes\", the shortest occurring sequences in each of 45,785 organismal reference genomes, present in one genome and absent from every other examined genome. In the human genome, we find that the genomic loci of nucleic quasi-primes are most enriched for genes associated with brain development and cognitive function. In a single-cell case study focusing on the human primary motor cortex, nucleic quasi-prime genes account for a significantly larger proportion of the variation based on average gene expression. Non-neuronal cell types, including astrocytes, endothelial cells, microglia perivascular-macrophages, oligodendrocytes, and vascular and leptomeningeal cells, exhibited significant activation of quasi-prime containing gene associations related to cancer, while simultaneously suppressing quasi-prime containing genes were associated with cognitive, mental, and developmental disorders. We also show that human disease-causing variants, eQTLs, mQTLs and sQTLs are 4.43-fold, 4.34-fold, 4.29-fold and 4.21-fold enriched at human quasi-prime loci, respectively. These findings indicate that nucleic quasi-primes are genomic loci linked to the evolution of species-specific traits and in humans they provide insights in the development of cognitive traits and human diseases, including neurodevelopmental disorders.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"134 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142911664","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