NAR Genomics and Bioinformatics最新文献

A general kernel machine regression framework using principal component analysis for jointly testing main and interaction effects: Applications to human microbiome studies. 利用主成分分析联合测试主效应和交互效应的通用核机器回归框架：应用于人类微生物组研究。

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NAR Genomics and Bioinformatics Pub Date : 2024-11-12 eCollection Date: 2024-09-01 DOI: 10.1093/nargab/lqae148

Hyunwook Koh

{"title":"A general kernel machine regression framework using principal component analysis for jointly testing main and interaction effects: Applications to human microbiome studies.","authors":"Hyunwook Koh","doi":"10.1093/nargab/lqae148","DOIUrl":"https://doi.org/10.1093/nargab/lqae148","url":null,"abstract":"The effect of a treatment on a health or disease response can be modified by genetic or microbial variants. It is the matter of interaction effects between genetic or microbial variants and a treatment. To powerfully discover genetic or microbial biomarkers, it is crucial to incorporate such interaction effects in addition to the main effects. However, in the context of kernel machine regression analysis of its kind, existing methods cannot be utilized in a situation, where a kernel is available but its underlying real variants are unknown. To address such limitations, I introduce a general kernel machine regression framework using principal component analysis for jointly testing main and interaction effects. It begins with extracting principal components from an input kernel through the singular value decomposition. Then, it employs the principal components as surrogate variants to construct three endogenous kernels for the main effects, interaction effects, and both of them, respectively. Hence, it works with a kernel as an input without knowing its underlying real variants, and also detects either the main effects, interaction effects, or both of them robustly. I also introduce its omnibus testing extension to multiple input kernels, named OmniK. I demonstrate its use for human microbiome studies.","PeriodicalId":33994,"journal":{"name":"NAR Genomics and Bioinformatics","volume":"6 4","pages":"lqae148"},"PeriodicalIF":4.0,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11555437/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142629627","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

Refining SARS-CoV-2 intra-host variation by leveraging large-scale sequencing data. 利用大规模测序数据完善 SARS-CoV-2 宿主内变异。

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NAR Genomics and Bioinformatics Pub Date : 2024-11-12 eCollection Date: 2024-09-01 DOI: 10.1093/nargab/lqae145

Fatima Mostefai, Jean-Christophe Grenier, Raphaël Poujol, Julie Hussin

{"title":"Refining SARS-CoV-2 intra-host variation by leveraging large-scale sequencing data.","authors":"Fatima Mostefai, Jean-Christophe Grenier, Raphaël Poujol, Julie Hussin","doi":"10.1093/nargab/lqae145","DOIUrl":"https://doi.org/10.1093/nargab/lqae145","url":null,"abstract":"Understanding viral genome evolution during host infection is crucial for grasping viral diversity and evolution. Analyzing intra-host single nucleotide variants (iSNVs) offers insights into new lineage emergence, which is important for predicting and mitigating future viral threats. Despite next-generation sequencing's potential, challenges persist, notably sequencing artifacts leading to false iSNVs. We developed a workflow to enhance iSNV detection in large NGS libraries, using over 130 000 SARS-CoV-2 libraries to distinguish mutations from errors. Our approach integrates bioinformatics protocols, stringent quality control, and dimensionality reduction to tackle batch effects and improve mutation detection reliability. Additionally, we pioneer the application of the PHATE visualization approach to genomic data and introduce a methodology that quantifies how related groups of data points are represented within a two-dimensional space, enhancing clustering structure explanation based on genetic similarities. This workflow advances accurate intra-host mutation detection, facilitating a deeper understanding of viral diversity and evolution.","PeriodicalId":33994,"journal":{"name":"NAR Genomics and Bioinformatics","volume":"6 4","pages":"lqae145"},"PeriodicalIF":4.0,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11555433/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142629558","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

Comparative single-cell transcriptomic analysis reveals putative differentiation drivers and potential origin of vertebrate retina. 单细胞转录组比较分析揭示了脊椎动物视网膜的推定分化驱动因素和潜在起源。

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NAR Genomics and Bioinformatics Pub Date : 2024-11-12 eCollection Date: 2024-09-01 DOI: 10.1093/nargab/lqae149

Xin Zeng, Fuki Gyoja, Yang Cui, Martin Loza, Takehiro G Kusakabe, Kenta Nakai

{"title":"Comparative single-cell transcriptomic analysis reveals putative differentiation drivers and potential origin of vertebrate retina.","authors":"Xin Zeng, Fuki Gyoja, Yang Cui, Martin Loza, Takehiro G Kusakabe, Kenta Nakai","doi":"10.1093/nargab/lqae149","DOIUrl":"https://doi.org/10.1093/nargab/lqae149","url":null,"abstract":"Despite known single-cell expression profiles in vertebrate retinas, understanding of their developmental and evolutionary expression patterns among homologous cell classes remains limited. We examined and compared approximately 240 000 retinal cells from four species and found significant similarities among homologous cell classes, indicating inherent regulatory patterns. To understand these shared patterns, we constructed gene regulatory networks for each developmental stage for three of these species. We identified 690 regulons governed by 530 regulators across three species, along with 10 common cell class-specific regulators and 16 highly preserved regulons. RNA velocity analysis pinpointed conserved putative driver genes and regulators to retinal cell differentiation in both mouse and zebrafish. Investigation of the origins of retinal cells by examining conserved expression patterns between vertebrate retinal cells and invertebrate Ciona intestinalis photoreceptor-related cells implied functional similarities in light transduction mechanisms. Our findings offer insights into the evolutionarily conserved regulatory frameworks and differentiation drivers of vertebrate retinal cells.","PeriodicalId":33994,"journal":{"name":"NAR Genomics and Bioinformatics","volume":"6 4","pages":"lqae149"},"PeriodicalIF":4.0,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11555436/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142629628","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

Diverse intrinsic properties shape transcript stability and stabilization in Mycolicibacterium smegmatis. 多种内在特性决定了烟曲霉中转录本的稳定性和稳定性。

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NAR Genomics and Bioinformatics Pub Date : 2024-11-04 eCollection Date: 2024-09-01 DOI: 10.1093/nargab/lqae147

Huaming Sun, Diego A Vargas-Blanco, Ying Zhou, Catherine S Masiello, Jessica M Kelly, Justin K Moy, Dmitry Korkin, Scarlet S Shell

{"title":"Diverse intrinsic properties shape transcript stability and stabilization in Mycolicibacterium smegmatis.","authors":"Huaming Sun, Diego A Vargas-Blanco, Ying Zhou, Catherine S Masiello, Jessica M Kelly, Justin K Moy, Dmitry Korkin, Scarlet S Shell","doi":"10.1093/nargab/lqae147","DOIUrl":"10.1093/nargab/lqae147","url":null,"abstract":"Mycobacteria regulate transcript degradation to facilitate adaptation to environmental stress. However, the mechanisms underlying this regulation are unknown. Here we sought to gain understanding of the mechanisms controlling mRNA stability by investigating the transcript properties associated with variance in transcript stability and stress-induced transcript stabilization. We measured mRNA half-lives transcriptome-wide in Mycolicibacterium smegmatis in log phase growth and hypoxia-induced growth arrest. The transcriptome was globally stabilized in response to hypoxia, but transcripts of essential genes were generally stabilized more than those of non-essential genes. We then developed machine learning models that enabled us to identify the non-linear collective effect of a compendium of transcript properties on transcript stability and stabilization. We identified properties that were more predictive of half-life in log phase as well as properties that were more predictive in hypoxia, and many of these varied between leadered and leaderless transcripts. In summary, we found that transcript properties are differentially associated with transcript stability depending on both the transcript type and the growth condition. Our results reveal the complex interplay between transcript features and microenvironment that shapes transcript stability in mycobacteria.","PeriodicalId":33994,"journal":{"name":"NAR Genomics and Bioinformatics","volume":"6 4","pages":"lqae147"},"PeriodicalIF":4.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11532794/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142577052","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

Faster and more accurate assessment of differential transcript expression with Gibbs sampling and edgeR v4. 利用 Gibbs 采样和 edgeR v4 更快、更准确地评估差异转录本表达。

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NAR Genomics and Bioinformatics Pub Date : 2024-11-04 eCollection Date: 2024-09-01 DOI: 10.1093/nargab/lqae151

Pedro L Baldoni, Lizhong Chen, Gordon K Smyth

{"title":"Faster and more accurate assessment of differential transcript expression with Gibbs sampling and edgeR v4.","authors":"Pedro L Baldoni, Lizhong Chen, Gordon K Smyth","doi":"10.1093/nargab/lqae151","DOIUrl":"10.1093/nargab/lqae151","url":null,"abstract":"This article further develops edgeR's divided-count approach for differential transcript expression (DTE) analysis of RNA-seq data to produce a faster and more accurate pipeline. The divided-count approach models the precision of transcript quantifications from the kallisto and Salmon software tools and divides the estimated overdispersions out of the transcript read counts, after which the divided-counts can be analysed by statistical tools developed for gene-level counts. This article adds three new refinements to the pipeline that dramatically decrease the computational overhead and storage requirements so that DTE analysis of very large datasets becomes practical. The new pipeline replaces bootstrap with Gibbs resampling and replaces edgeR v3 with v4. Both of these changes improve statistical power and accuracy and provide better resolution for low-count transcripts. The accuracy of overdispersion estimation is shown to depend on the total number of resamples across the whole dataset rather than on individual samples, dramatically reducing the recommended number of technical samples for large datasets. Test data and extensive simulations data show that the new pipeline is more powerful and efficient than previous DTE pipelines while providing correct control of the false discovery rate for any sample size.","PeriodicalId":33994,"journal":{"name":"NAR Genomics and Bioinformatics","volume":"6 4","pages":"lqae151"},"PeriodicalIF":4.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11532793/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142577054","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

Tumor purity estimated from bulk DNA methylation can be used for adjusting beta values of individual samples to better reflect tumor biology. 根据大量 DNA 甲基化估计的肿瘤纯度可用于调整单个样本的 beta 值，以更好地反映肿瘤生物学特性。

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NAR Genomics and Bioinformatics Pub Date : 2024-11-04 eCollection Date: 2024-09-01 DOI: 10.1093/nargab/lqae146

Iñaki Sasiain, Deborah F Nacer, Mattias Aine, Srinivas Veerla, Johan Staaf

{"title":"Tumor purity estimated from bulk DNA methylation can be used for adjusting beta values of individual samples to better reflect tumor biology.","authors":"Iñaki Sasiain, Deborah F Nacer, Mattias Aine, Srinivas Veerla, Johan Staaf","doi":"10.1093/nargab/lqae146","DOIUrl":"10.1093/nargab/lqae146","url":null,"abstract":"Epigenetic deregulation through altered DNA methylation is a fundamental feature of tumorigenesis, but tumor data from bulk tissue samples contain different proportions of malignant and non-malignant cells that may confound the interpretation of DNA methylation values. The adjustment of DNA methylation data based on tumor purity has been proposed to render both genome-wide and gene-specific analyses more precise, but it requires sample purity estimates. Here we present PureBeta, a single-sample statistical framework that uses genome-wide DNA methylation data to first estimate sample purity and then adjust methylation values of individual CpGs to correct for sample impurity. Purity values estimated with the algorithm have high correlation (>0.8) to reference values obtained from DNA sequencing when applied to samples from breast carcinoma, lung adenocarcinoma, and lung squamous cell carcinoma. Methylation beta values adjusted based on purity estimates have a more binary distribution that better reflects theoretical methylation states, thus facilitating improved biological inference as shown for BRCA1 in breast cancer. PureBeta is a versatile tool that can be used for different Illumina DNA methylation arrays and can be applied to individual samples of different cancer types to enhance biological interpretability of methylation data.","PeriodicalId":33994,"journal":{"name":"NAR Genomics and Bioinformatics","volume":"6 4","pages":"lqae146"},"PeriodicalIF":4.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11532792/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142577055","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

Intronic RNA secondary structural information captured for the human MYC pre-mRNA. 捕捉到的人类 MYC 前核糖核酸内部二级结构信息。

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NAR Genomics and Bioinformatics Pub Date : 2024-10-24 eCollection Date: 2024-09-01 DOI: 10.1093/nargab/lqae143

Taylor O Eich, Collin A O'Leary, Walter N Moss

{"title":"Intronic RNA secondary structural information captured for the human MYC pre-mRNA.","authors":"Taylor O Eich, Collin A O'Leary, Walter N Moss","doi":"10.1093/nargab/lqae143","DOIUrl":"https://doi.org/10.1093/nargab/lqae143","url":null,"abstract":"To address the lack of intronic reads in secondary structure probing data for the human MYC pre-mRNA, we developed a method that combines spliceosomal inhibition with RNA probing and sequencing. Here, the SIRP-seq method was applied to study the secondary structure of human MYC RNAs by chemically probing HeLa cells with dimethyl sulfate in the presence of the small molecule spliceosome inhibitor pladienolide B. Pladienolide B binds to the SF3B complex of the spliceosome to inhibit intron removal during splicing, resulting in retained intronic sequences. This method was used to increase the read coverage over intronic regions of MYC. The purpose for increasing coverage across introns was to generate complete reactivity profiles for intronic sequences via the DMS-MaPseq approach. Notably, depth was sufficient for analysis by the program DRACO, which was able to deduce distinct reactivity profiles and predict multiple secondary structural conformations as well as their suggested stoichiometric abundances. The results presented here provide a new method for intronic RNA secondary structural analyses, as well as specific structural insights relevant to MYC RNA splicing regulation and therapeutic targeting.","PeriodicalId":33994,"journal":{"name":"NAR Genomics and Bioinformatics","volume":"6 4","pages":"lqae143"},"PeriodicalIF":4.0,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11500451/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142509478","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 next-generation sequencing-chess problem. 下一代测序-国际象棋问题。

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NAR Genomics and Bioinformatics Pub Date : 2024-10-24 eCollection Date: 2024-09-01 DOI: 10.1093/nargab/lqae144

Leo Zeitler, Arach Goldar, Cyril Denby Wilkes, Julie Soutourina

引用次数: 0

Graphite: painting genomes using a colored de Bruijn graph. 石墨：使用彩色德布鲁因图绘制基因组。

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NAR Genomics and Bioinformatics Pub Date : 2024-10-23 eCollection Date: 2024-09-01 DOI: 10.1093/nargab/lqae142

Rick Beeloo, Aldert L Zomer, Sebastian Deorowicz, Bas E Dutilh

引用次数: 0

MoNETA: MultiOmics Network Embedding for SubType Analysis. MoNETA：用于子类型分析的多声学网络嵌入。

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NAR Genomics and Bioinformatics Pub Date : 2024-10-16 eCollection Date: 2024-09-01 DOI: 10.1093/nargab/lqae141

Giovanni Scala, Luigi Ferraro, Aurora Brandi, Yan Guo, Barbara Majello, Michele Ceccarelli

引用次数: 0