NAR Genomics and Bioinformatics最新文献_第3页

asms: finding allele-specific methylation in human genomes without phasing. asm：在人类基因组中发现没有相位的等位基因特异性甲基化。

IF 3

NAR Genomics and Bioinformatics Pub Date : 2026-07-02 eCollection Date: 2026-09-01 DOI: 10.1093/nargab/lqag072

Emanuele Raineri, Miguel Ángel Esteve Marco, Eloi Casals, Anna Esteve Codina

{"title":"asms: finding allele-specific methylation in human genomes without phasing.","authors":"Emanuele Raineri, Miguel Ángel Esteve Marco, Eloi Casals, Anna Esteve Codina","doi":"10.1093/nargab/lqag072","DOIUrl":"10.1093/nargab/lqag072","url":null,"abstract":"Allele-specific methylation (ASM) refers to the differential DNA methylation between two alleles at a specific locus. This phenomenon can be driven by genomic imprinting (where gene expression depends on the parent of origin) or by genetic variants (that may affect DNA-protein binding), both of which play crucial roles in gene regulation and contribute to normal biological variation and disease. ASM can be tissue- or cell-type specific, which adds an extra layer of complexity to its analysis. Detection methods typically rely on phasing using genetic variants, a process that is computationally intensive and can fail in regions with low heterozygosity. To overcome these limitations, we developed asms (Allele-Specific Methylation Scanner), a tool that identifies potential ASM loci from methylation data without requiring prior phasing by looking at heterogeneous methylation across reads. Although we tested it using Oxford Nanopore Technologies (ONT) data, the tool can be used with any platform using MM/ML tags to store methylation in BAM files. asms can examine efficiently thousands of loci (either from a list or through an automatic genomic scan) by segregating reads based on their methylation patterns. When information on variants is available, asms can verify whether distinct alleles correspond to different base modification profiles. asms is available at https://github.com/ecmra/asms.","PeriodicalId":33994,"journal":{"name":"NAR Genomics and Bioinformatics","volume":"8 3","pages":"lqag072"},"PeriodicalIF":3.0,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13326645/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148377056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The role of ATF4 in neurons under mitochondrial stress. 线粒体应激下ATF4在神经元中的作用。

IF 3

NAR Genomics and Bioinformatics Pub Date : 2026-06-30 eCollection Date: 2026-09-01 DOI: 10.1093/nargab/lqag069

Maria Bilen, Yubing Liu, Imane Chakroun, Mohamed Ariff Iqbal, Bensun C Fong, Jingwei Chen, Smitha Paul, Alexandre Blais, Ruth S Slack

{"title":"The role of ATF4 in neurons under mitochondrial stress.","authors":"Maria Bilen, Yubing Liu, Imane Chakroun, Mohamed Ariff Iqbal, Bensun C Fong, Jingwei Chen, Smitha Paul, Alexandre Blais, Ruth S Slack","doi":"10.1093/nargab/lqag069","DOIUrl":"10.1093/nargab/lqag069","url":null,"abstract":"Mitochondrial dysfunction and fragmentation are observed in various circumstances, such as neurodegeneration and aging. Studies have shown that altered mitochondrial function activates the integrated stress response (ISR), with ATF4 serving as a major mediator of adaptation to stress. Presently, little is known about the role of ATF4 in neurons under mitochondrial stress. Using primary cortical neurons, we demonstrate that inhibiting ATF4 under OPA1-mediated mitochondrial stress accelerates the impairment of neuronal differentiation, as evidenced by smaller dendrites and lower dendritic spine density. To better understand the role of ATF4 in this context, we investigated the global binding sites of ATF4 using chromatin immunoprecipitation sequencing (ChIP-seq) and examined the chromatin accessibility changes that occur following the loss of ATF4 in neurons under conditions of mitochondrial stress. We found that ATF4 binds to a wide range of targets and alters the chromatin accessibility of genes involved in metabolism, neuronal fate, and neuron maturation. The downstream targets of ATF4 identified in this study can reveal novel and direct targets of ATF4 in neuronal survival and maturation. These adaptations are the hallmarks of stress response in mitochondrial dysfunction-mediated neurodegeneration.","PeriodicalId":33994,"journal":{"name":"NAR Genomics and Bioinformatics","volume":"8 3","pages":"lqag069"},"PeriodicalIF":3.0,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13316428/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148362802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

An epigenetic clock for chronological age estimation in East Asian populations. 东亚人群实足年龄估计的表观遗传时钟。

IF 3

NAR Genomics and Bioinformatics Pub Date : 2026-06-30 eCollection Date: 2026-09-01 DOI: 10.1093/nargab/lqag068

Kuan Chen Lu, Po-Hsiu Kuo, Amrita Chattopadhyay, Tzu-Pin Lu

{"title":"An epigenetic clock for chronological age estimation in East Asian populations.","authors":"Kuan Chen Lu, Po-Hsiu Kuo, Amrita Chattopadhyay, Tzu-Pin Lu","doi":"10.1093/nargab/lqag068","DOIUrl":"10.1093/nargab/lqag068","url":null,"abstract":"Population aging is increasing the burden of age-related disease, highlighting the need for accurate molecular tools to estimate aging. DNA methylation, a heritable epigenetic mark linked to development and age-related disease, can capture biological aging and predict chronological age; however, most existing epigenetic clocks were developed primarily in non-East Asian populations and may show reduced calibration across ancestries. We analyzed methylation profiles from East Asian cohorts from Taiwan, Japan, and China to develop an East Asian-specific epigenetic clock, termed the EAS Clock. After quality control and probe filtering, a parsimonious model based on 38 CpG sites was constructed using stepwise multivariate regression with forward selection and Bayesian Information Criterion. The EAS Clock showed significant correlations between predicted and chronological age in both training and independent testing datasets, with residuals centered near zero. Functional enrichment analyses indicated that genes associated with the selected CpGs were involved in neurobiological, musculoskeletal, immune-inflammatory, and lipid-metabolic pathways. These findings support the EAS Clock as a compact methylation-based estimator of chronological age tailored to East Asian populations.","PeriodicalId":33994,"journal":{"name":"NAR Genomics and Bioinformatics","volume":"8 3","pages":"lqag068"},"PeriodicalIF":3.0,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13316434/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148362793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Long non-coding RNA triplex-dependent regulation of melanoma gene networks. 黑色素瘤基因网络的长链非编码RNA三联体依赖性调控。

IF 3

NAR Genomics and Bioinformatics Pub Date : 2026-06-27 eCollection Date: 2026-09-01 DOI: 10.1093/nargab/lqag067

Kushani Shah, Eleni Anastasakou, Leinal Sejour, Serafima Guseva, Christopher Rauchet, Leon Wert-Lamas, Riccardo Calandrelli, Robert Distel, Sheng Zhong, Ioannis Vlachos, Carl D Novina

{"title":"Long non-coding RNA triplex-dependent regulation of melanoma gene networks.","authors":"Kushani Shah, Eleni Anastasakou, Leinal Sejour, Serafima Guseva, Christopher Rauchet, Leon Wert-Lamas, Riccardo Calandrelli, Robert Distel, Sheng Zhong, Ioannis Vlachos, Carl D Novina","doi":"10.1093/nargab/lqag067","DOIUrl":"10.1093/nargab/lqag067","url":null,"abstract":"SLNCR is a long non-coding RNA (lncRNA) that promotes melanoma formation. Previously, we have shown that SLNCR regulates gene expression via its interactions with different transcription factors. Here we show that SLNCR is associated with several genomic sites that contain RNA•DNA triplex target sites (TTSs). The primary sequence of SLNCR contains four triplex-forming regions (TFRs), which are homologous to the TFRs of MEG3, HOTAIR, and PARTICLE lncRNAs. Full-length SLNCR overexpression promotes proliferation, migration, and invasion of melanoma cells by inducing characteristic gene expression changes of genes that are enriched in pathways involved in cell cycle regulation and cell migration. The transcriptomic signature of full-length SLNCR is reversed by deletions of TFR1, 2, 3, or 4. Full-length SLNCR is structurally flexible and permissive of different interactions with the DNA and/or proteins. Deletion of any individual TFR causes SLNCR to gain structural definition, potentially preventing some of its native interactions. Using RNA sequencing and the Triplex Domain Finder tool, we demonstrate that SLNCR TFRs form RNA•DNA:DNA triplexes with the TTSs in promoters of key genes (nodes) predicted to regulate melanoma migration and invasion networks. We further validate the effect on invasion using A375 cells in functional assays. Finally, inhibitory oligos that block SLNCR•DNA:DNA triplex formation reversed the effect of SLNCR-mediated migration ex vivo, demonstrating that triplex formation plays a role in driving melanoma progression.","PeriodicalId":33994,"journal":{"name":"NAR Genomics and Bioinformatics","volume":"8 3","pages":"lqag067"},"PeriodicalIF":3.0,"publicationDate":"2026-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13309845/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148346525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Distinct repeat architecture landscapes in the proteomes of protozoan parasites. 原生动物寄生虫蛋白质组中不同的重复结构景观。

IF 3

NAR Genomics and Bioinformatics Pub Date : 2026-06-27 eCollection Date: 2026-09-01 DOI: 10.1093/nargab/lqag061

Hirotaka Matsumoto, Jing Hong

{"title":"Distinct repeat architecture landscapes in the proteomes of protozoan parasites.","authors":"Hirotaka Matsumoto, Jing Hong","doi":"10.1093/nargab/lqag061","DOIUrl":"10.1093/nargab/lqag061","url":null,"abstract":"Protozoan parasites cause major infectious diseases and pose persistent global health challenges, particularly the emergence of drug-resistant strains. Tandem repeats and other repetitive architectures are widespread in proteomes and have been implicated in host-parasite interactions, immune evasion, and antigenicity. However, repeat-containing proteins (RPs) exhibit highly diverse architectures that extend beyond simple motif reiteration, making their comprehensive and quantitative characterization challenging. In this study, we performed bioinformatics analysis of repeat architectures in protozoan proteins. In addition to the established repeat-detection approaches, we developed a new algorithm, Drepper, which quantifies repeat-architecture complexity. By integrating diverse repeat-related features, we clustered RPs across species and identified distinct groups associated with parasite lineages. Notably, we identified a high-complexity, repeat-rich (HCRR) cluster enriched in Plasmodium proteins and a low-complexity, repeat-rich (LCRR) cluster enriched in Trypanosoma and Leishmania proteins. Functional, evolutionary, and structural analyses revealed that LCRR cluster is enriched in flagellar-related proteins, low-complexity repeat architectures may be maintained through concerted evolution, and, compared with HCRR, it shows a greater tendency to adopt defined three-dimensional structures. Taken together, our results reveal lineage-specific strategies in protozoan repeat architectures and provide a quantitative framework for studying their biological and evolutionary roles.","PeriodicalId":33994,"journal":{"name":"NAR Genomics and Bioinformatics","volume":"8 3","pages":"lqag061"},"PeriodicalIF":3.0,"publicationDate":"2026-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13309793/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148346594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Challenges in predicting chromatin accessibility differences between species. 预测物种间染色质可及性差异的挑战。

IF 3

NAR Genomics and Bioinformatics Pub Date : 2026-06-24 eCollection Date: 2026-06-01 DOI: 10.1093/nargab/lqag059

Amy Z M Stephen, Arian Raje, Heather H Sestili, Morgan E Wirthlin, Alyssa J Lawler, Ashley R Brown, Junjie Ma, William R Stauffer, Andreas R Pfenning, Irene M Kaplow

{"title":"Challenges in predicting chromatin accessibility differences between species.","authors":"Amy Z M Stephen, Arian Raje, Heather H Sestili, Morgan E Wirthlin, Alyssa J Lawler, Ashley R Brown, Junjie Ma, William R Stauffer, Andreas R Pfenning, Irene M Kaplow","doi":"10.1093/nargab/lqag059","DOIUrl":"10.1093/nargab/lqag059","url":null,"abstract":"Differences in enhancer activity between species can help drive phenotypic diversity, yet enhancers often have conserved functions despite rapid sequence evolution, posing a challenge for quantifying their functional differences between species. Previous machine learning models have focused on the binary task of predicting differences in the presence of enhancers between species but have yet to demonstrate an ability to predict continuous differences in enhancer activity. Here, we trained convolutional neural networks on a regression task to predict chromatin accessibility-a proxy for enhancer activity-in the liver across five mammals, and we developed a novel framework to evaluate cross-species performance. We demonstrated that training on multiple species improves model generalization to both species used in training and held-out species. However, the models consistently achieved poor performance in predicting quantitative differences in accessibility between species at orthologous regions. Our study highlights the challenges in using regression models to predict chromatin accessibility changes between species. All data and code are available at http://daphne.compbio.cs.cmu.edu/files/azstephe/liver_regression_resource/ and https://figshare.com/projects/liverRegression/274293.","PeriodicalId":33994,"journal":{"name":"NAR Genomics and Bioinformatics","volume":"8 2","pages":"lqag059"},"PeriodicalIF":3.0,"publicationDate":"2026-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13291610/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148333314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Power-law penalties correct distance bias in single-cell co-accessibility and deep-learning chromatin interaction predictions. 幂律惩罚纠正了单细胞共可及性和深度学习染色质相互作用预测中的距离偏差。

IF 3

NAR Genomics and Bioinformatics Pub Date : 2026-06-24 eCollection Date: 2026-06-01 DOI: 10.1093/nargab/lqag063

Luca Schlegel, Fabio Gómez Cano, Alexandre P Marand, Frank Johannes

引用次数: 0

LORA: a polymorphic multi-sample long read assembly pipeline. LORA：多态多样本长读组装管道。

IF 3

NAR Genomics and Bioinformatics Pub Date : 2026-06-23 eCollection Date: 2026-06-01 DOI: 10.1093/nargab/lqag062

Dimitri Desvillechabrol, Rania Ouazahrou, Juliana Pipoli da Fonseca, Gerald F Späth, Thomas Cokelaer

{"title":"LORA: a polymorphic multi-sample long read assembly pipeline.","authors":"Dimitri Desvillechabrol, Rania Ouazahrou, Juliana Pipoli da Fonseca, Gerald F Späth, Thomas Cokelaer","doi":"10.1093/nargab/lqag062","DOIUrl":"10.1093/nargab/lqag062","url":null,"abstract":"Genome assembly from long-read sequencing data has become a standard approach for resolving complex genomic regions and producing high-contiguity assemblies. However, the diversity of available assemblers, their varying performance across species, and the need for reproducible workflows present ongoing challenges. We developed LORA, an easy-to-use and reproducible application for assembling genomes from long-read data. LORA integrates several well-established assemblers, including Canu, HiFiasm, Flye, and Unicycler, as well as more recent tools such as Necat and Pecat. It is implemented as a Snakemake pipeline to parallelize tasks and support seamless execution on both local machines and computing clusters. LORA includes multiple quality assessment steps, interactive HTML reports for interpretation, BLAST-based taxonomic identification, and completeness evaluation. Together, these features provide users with a comprehensive view of assembly quality and potential problems. We illustrate the capabilities of LORA using datasets from bacterial genomes and unicellular eukaryotes, sequenced with both PacBio and Oxford Nanopore technologies, highlighting typical outcomes and common pitfalls encountered during long-read assemblies. LORA is distributed as part of the Sequana project, an open-source framework designed for reproducibility, maintainability, and straightforward deployment across computing environments.","PeriodicalId":33994,"journal":{"name":"NAR Genomics and Bioinformatics","volume":"8 2","pages":"lqag062"},"PeriodicalIF":3.0,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13288111/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148319572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Correction to 'Genome sequence assembly and annotation of MATA and MATB strains of Yarrowia lipolytica'. 对“多脂耶氏菌MATA和MATB菌株的基因组序列组装和注释”的更正。

IF 3

NAR Genomics and Bioinformatics Pub Date : 2026-06-22 eCollection Date: 2026-06-01 DOI: 10.1093/nargab/lqag064

引用次数: 0

Comprehensive mapping of identical sequences across human proteins emphasizes the widespread issue of shared epitopes in self-antigens. 对人类蛋白质中相同序列的全面定位强调了自体抗原中共享表位的广泛问题。

IF 3

NAR Genomics and Bioinformatics Pub Date : 2026-06-22 eCollection Date: 2026-06-01 DOI: 10.1093/nargab/lqag060

Guillaume Kellermann, Olivier Croce, Baharia Mograbi, Paul Hofman, Patrick Brest

引用次数: 0