Pub Date : 2024-04-22DOI: 10.1093/gigascience/giae017
Yiyan Yang, Keith Dufault-Thompson, Wei Yan, Tian Cai, Lei Xie, Xiaofang Jiang
Background Phage therapy, reemerging as a promising approach to counter antimicrobial-resistant infections, relies on a comprehensive understanding of the specificity of individual phages. Yet the significant diversity within phage populations presents a considerable challenge. Currently, there is a notable lack of tools designed for large-scale characterization of phage receptor-binding proteins, which are crucial in determining the phage host range. Results In this study, we present SpikeHunter, a deep learning method based on the ESM-2 protein language model. With SpikeHunter, we identified 231,965 diverse phage-encoded tailspike proteins, a crucial determinant of phage specificity that targets bacterial polysaccharide receptors, across 787,566 bacterial genomes from 5 virulent, antibiotic-resistant pathogens. Notably, 86.60% (143,200) of these proteins exhibited strong associations with specific bacterial polysaccharides. We discovered that phages with identical tailspike proteins can infect different bacterial species with similar polysaccharide receptors, underscoring the pivotal role of tailspike proteins in determining host range. The specificity is mainly attributed to the protein’s C-terminal domain, which strictly correlates with host specificity during domain swapping in tailspike proteins. Importantly, our dataset-driven predictions of phage–host specificity closely match the phage–host pairs observed in real-world phage therapy cases we studied. Conclusions Our research provides a rich resource, including both the method and a database derived from a large-scale genomics survey. This substantially enhances understanding of phage specificity determinants at the strain level and offers a valuable framework for guiding phage selection in therapeutic applications.
{"title":"Large-scale genomic survey with deep learning-based method reveals strain-level phage specificity determinants","authors":"Yiyan Yang, Keith Dufault-Thompson, Wei Yan, Tian Cai, Lei Xie, Xiaofang Jiang","doi":"10.1093/gigascience/giae017","DOIUrl":"https://doi.org/10.1093/gigascience/giae017","url":null,"abstract":"Background Phage therapy, reemerging as a promising approach to counter antimicrobial-resistant infections, relies on a comprehensive understanding of the specificity of individual phages. Yet the significant diversity within phage populations presents a considerable challenge. Currently, there is a notable lack of tools designed for large-scale characterization of phage receptor-binding proteins, which are crucial in determining the phage host range. Results In this study, we present SpikeHunter, a deep learning method based on the ESM-2 protein language model. With SpikeHunter, we identified 231,965 diverse phage-encoded tailspike proteins, a crucial determinant of phage specificity that targets bacterial polysaccharide receptors, across 787,566 bacterial genomes from 5 virulent, antibiotic-resistant pathogens. Notably, 86.60% (143,200) of these proteins exhibited strong associations with specific bacterial polysaccharides. We discovered that phages with identical tailspike proteins can infect different bacterial species with similar polysaccharide receptors, underscoring the pivotal role of tailspike proteins in determining host range. The specificity is mainly attributed to the protein’s C-terminal domain, which strictly correlates with host specificity during domain swapping in tailspike proteins. Importantly, our dataset-driven predictions of phage–host specificity closely match the phage–host pairs observed in real-world phage therapy cases we studied. Conclusions Our research provides a rich resource, including both the method and a database derived from a large-scale genomics survey. This substantially enhances understanding of phage specificity determinants at the strain level and offers a valuable framework for guiding phage selection in therapeutic applications.","PeriodicalId":12581,"journal":{"name":"GigaScience","volume":"41 1","pages":""},"PeriodicalIF":9.2,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140804820","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}
Background Most currently available reference genomes lack the sequence map of sex-limited (such as Y and W) chromosomes, which results in incomplete assemblies that hinder further research on sex chromosomes. Recent advancements in long-read sequencing and population sequencing have provided the opportunity to assemble sex-limited chromosomes without the traditional complicated experimental efforts. Findings We introduce the first computational method, Sorting long Reads of Y or other sex-limited chromosome (SRY), which achieves improved assembly results compared to flow sorting. Specifically, SRY outperforms in the heterochromatic region and demonstrates comparable performance in other regions. Furthermore, SRY enhances the capabilities of the hybrid assembly software, resulting in improved continuity and accuracy. Conclusions Our method enables true complete genome assembly and facilitates downstream research of sex-limited chromosomes.
背景 目前可用的大多数参考基因组都缺乏性限（如 Y 和 W）染色体的序列图，导致组装不完整，阻碍了对性染色体的进一步研究。最近在长线程测序和群体测序方面取得的进展为我们提供了无需传统的复杂实验工作就能组装性限染色体的机会。研究结果 我们介绍了第一种计算方法--Y或其他性别限制染色体长读数排序法（SRY），与流式排序法相比，SRY的组装结果更好。具体来说，SRY 在异染色质区域的表现更好，在其他区域的表现也不相上下。此外，SRY 还增强了混合组装软件的功能，从而提高了连续性和准确性。结论 我们的方法实现了真正的全基因组组装，并促进了性别限制染色体的下游研究。
{"title":"An effective strategy for assembling the sex-limited chromosome","authors":"Xiao-Bo Wang, Hong-Wei Lu, Qing-You Liu, A-Lun Li, Hong-Ling Zhou, Yong Zhang, Tian-Qi Zhu, Jue Ruan","doi":"10.1093/gigascience/giae015","DOIUrl":"https://doi.org/10.1093/gigascience/giae015","url":null,"abstract":"Background Most currently available reference genomes lack the sequence map of sex-limited (such as Y and W) chromosomes, which results in incomplete assemblies that hinder further research on sex chromosomes. Recent advancements in long-read sequencing and population sequencing have provided the opportunity to assemble sex-limited chromosomes without the traditional complicated experimental efforts. Findings We introduce the first computational method, Sorting long Reads of Y or other sex-limited chromosome (SRY), which achieves improved assembly results compared to flow sorting. Specifically, SRY outperforms in the heterochromatic region and demonstrates comparable performance in other regions. Furthermore, SRY enhances the capabilities of the hybrid assembly software, resulting in improved continuity and accuracy. Conclusions Our method enables true complete genome assembly and facilitates downstream research of sex-limited chromosomes.","PeriodicalId":12581,"journal":{"name":"GigaScience","volume":"21 1","pages":""},"PeriodicalIF":9.2,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140613961","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}
Pub Date : 2024-04-16DOI: 10.1093/gigascience/giae019
Hamid Beiki, Brenda M Murdoch, Carissa A Park, Chandlar Kern, Denise Kontechy, Gabrielle Becker, Gonzalo Rincon, Honglin Jiang, Huaijun Zhou, Jacob Thorne, James E Koltes, Jennifer J Michal, Kimberly Davenport, Monique Rijnkels, Pablo J Ross, Rui Hu, Sarah Corum, Stephanie McKay, Timothy P L Smith, Wansheng Liu, Wenzhi Ma, Xiaohui Zhang, Xiaoqing Xu, Xuelei Han, Zhihua Jiang, Zhi-Liang Hu, James M Reecy
Background The accurate identification of the functional elements in the bovine genome is a fundamental requirement for high-quality analysis of data informing both genome biology and genomic selection. Functional annotation of the bovine genome was performed to identify a more complete catalog of transcript isoforms across bovine tissues. Results A total of 160,820 unique transcripts (50% protein coding) representing 34,882 unique genes (60% protein coding) were identified across tissues. Among them, 118,563 transcripts (73% of the total) were structurally validated by independent datasets (PacBio isoform sequencing data, Oxford Nanopore Technologies sequencing data, de novo assembled transcripts from RNA sequencing data) and comparison with Ensembl and NCBI gene sets. In addition, all transcripts were supported by extensive data from different technologies such as whole transcriptome termini site sequencing, RNA Annotation and Mapping of Promoters for the Analysis of Gene Expression, chromatin immunoprecipitation sequencing, and assay for transposase-accessible chromatin using sequencing. A large proportion of identified transcripts (69%) were unannotated, of which 86% were produced by annotated genes and 14% by unannotated genes. A median of two 5′ untranslated regions were expressed per gene. Around 50% of protein-coding genes in each tissue were bifunctional and transcribed both coding and noncoding isoforms. Furthermore, we identified 3,744 genes that functioned as noncoding genes in fetal tissues but as protein-coding genes in adult tissues. Our new bovine genome annotation extended more than 11,000 annotated gene borders compared to Ensembl or NCBI annotations. The resulting bovine transcriptome was integrated with publicly available quantitative trait loci data to study tissue–tissue interconnection involved in different traits and construct the first bovine trait similarity network. Conclusions These validated results show significant improvement over current bovine genome annotations.
{"title":"Enhanced bovine genome annotation through integration of transcriptomics and epi-transcriptomics datasets facilitates genomic biology","authors":"Hamid Beiki, Brenda M Murdoch, Carissa A Park, Chandlar Kern, Denise Kontechy, Gabrielle Becker, Gonzalo Rincon, Honglin Jiang, Huaijun Zhou, Jacob Thorne, James E Koltes, Jennifer J Michal, Kimberly Davenport, Monique Rijnkels, Pablo J Ross, Rui Hu, Sarah Corum, Stephanie McKay, Timothy P L Smith, Wansheng Liu, Wenzhi Ma, Xiaohui Zhang, Xiaoqing Xu, Xuelei Han, Zhihua Jiang, Zhi-Liang Hu, James M Reecy","doi":"10.1093/gigascience/giae019","DOIUrl":"https://doi.org/10.1093/gigascience/giae019","url":null,"abstract":"Background The accurate identification of the functional elements in the bovine genome is a fundamental requirement for high-quality analysis of data informing both genome biology and genomic selection. Functional annotation of the bovine genome was performed to identify a more complete catalog of transcript isoforms across bovine tissues. Results A total of 160,820 unique transcripts (50% protein coding) representing 34,882 unique genes (60% protein coding) were identified across tissues. Among them, 118,563 transcripts (73% of the total) were structurally validated by independent datasets (PacBio isoform sequencing data, Oxford Nanopore Technologies sequencing data, de novo assembled transcripts from RNA sequencing data) and comparison with Ensembl and NCBI gene sets. In addition, all transcripts were supported by extensive data from different technologies such as whole transcriptome termini site sequencing, RNA Annotation and Mapping of Promoters for the Analysis of Gene Expression, chromatin immunoprecipitation sequencing, and assay for transposase-accessible chromatin using sequencing. A large proportion of identified transcripts (69%) were unannotated, of which 86% were produced by annotated genes and 14% by unannotated genes. A median of two 5′ untranslated regions were expressed per gene. Around 50% of protein-coding genes in each tissue were bifunctional and transcribed both coding and noncoding isoforms. Furthermore, we identified 3,744 genes that functioned as noncoding genes in fetal tissues but as protein-coding genes in adult tissues. Our new bovine genome annotation extended more than 11,000 annotated gene borders compared to Ensembl or NCBI annotations. The resulting bovine transcriptome was integrated with publicly available quantitative trait loci data to study tissue–tissue interconnection involved in different traits and construct the first bovine trait similarity network. Conclusions These validated results show significant improvement over current bovine genome annotations.","PeriodicalId":12581,"journal":{"name":"GigaScience","volume":"19 1","pages":""},"PeriodicalIF":9.2,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140614176","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}
Pub Date : 2024-04-16DOI: 10.1093/gigascience/giae014
Sungwon Jeon, Hansol Choi, Yeonsu Jeon, Whan-Hyuk Choi, Hyunjoo Choi, Kyungwhan An, Hyojung Ryu, Jihun Bhak, Hyeonjae Lee, Yoonsung Kwon, Sukyeon Ha, Yeo Jin Kim, Asta Blazyte, Changjae Kim, Yeonkyung Kim, Younghui Kang, Yeong Ju Woo, Chanyoung Lee, Jeongwoo Seo, Changhan Yoon, Dan Bolser, Orsolya Biro, Eun-Seok Shin, Byung Chul Kim, Seon-Young Kim, Ji-Hwan Park, Jongbum Jeon, Dooyoung Jung, Semin Lee, Jong Bhak
Background Phenome-wide association studies (PheWASs) have been conducted on Asian populations, including Koreans, but many were based on chip or exome genotyping data. Such studies have limitations regarding whole genome–wide association analysis, making it crucial to have genome-to-phenome association information with the largest possible whole genome and matched phenome data to conduct further population-genome studies and develop health care services based on population genomics. Results Here, we present 4,157 whole genome sequences (Korea4K) coupled with 107 health check-up parameters as the largest genomic resource of the Korean Genome Project. It encompasses most of the variants with allele frequency >0.001 in Koreans, indicating that it sufficiently covered most of the common and rare genetic variants with commonly measured phenotypes for Koreans. Korea4K provides 45,537,252 variants, and half of them were not present in Korea1K (1,094 samples). We also identified 1,356 new genotype–phenotype associations that were not found by the Korea1K dataset. Phenomics analyses further revealed 24 significant genetic correlations, 14 pleiotropic associations, and 127 causal relationships based on Mendelian randomization among 37 traits. In addition, the Korea4K imputation reference panel, the largest Korean variants reference to date, showed a superior imputation performance to Korea1K across all allele frequency categories. Conclusions Collectively, Korea4K provides not only the largest Korean genome data but also corresponding health check-up parameters and novel genome–phenome associations. The large-scale pathological whole genome–wide omics data will become a powerful set for genome–phenome level association studies to discover causal markers for the prediction and diagnosis of health conditions in future studies.
{"title":"Korea4K: whole genome sequences of 4,157 Koreans with 107 phenotypes derived from extensive health check-ups","authors":"Sungwon Jeon, Hansol Choi, Yeonsu Jeon, Whan-Hyuk Choi, Hyunjoo Choi, Kyungwhan An, Hyojung Ryu, Jihun Bhak, Hyeonjae Lee, Yoonsung Kwon, Sukyeon Ha, Yeo Jin Kim, Asta Blazyte, Changjae Kim, Yeonkyung Kim, Younghui Kang, Yeong Ju Woo, Chanyoung Lee, Jeongwoo Seo, Changhan Yoon, Dan Bolser, Orsolya Biro, Eun-Seok Shin, Byung Chul Kim, Seon-Young Kim, Ji-Hwan Park, Jongbum Jeon, Dooyoung Jung, Semin Lee, Jong Bhak","doi":"10.1093/gigascience/giae014","DOIUrl":"https://doi.org/10.1093/gigascience/giae014","url":null,"abstract":"Background Phenome-wide association studies (PheWASs) have been conducted on Asian populations, including Koreans, but many were based on chip or exome genotyping data. Such studies have limitations regarding whole genome–wide association analysis, making it crucial to have genome-to-phenome association information with the largest possible whole genome and matched phenome data to conduct further population-genome studies and develop health care services based on population genomics. Results Here, we present 4,157 whole genome sequences (Korea4K) coupled with 107 health check-up parameters as the largest genomic resource of the Korean Genome Project. It encompasses most of the variants with allele frequency >0.001 in Koreans, indicating that it sufficiently covered most of the common and rare genetic variants with commonly measured phenotypes for Koreans. Korea4K provides 45,537,252 variants, and half of them were not present in Korea1K (1,094 samples). We also identified 1,356 new genotype–phenotype associations that were not found by the Korea1K dataset. Phenomics analyses further revealed 24 significant genetic correlations, 14 pleiotropic associations, and 127 causal relationships based on Mendelian randomization among 37 traits. In addition, the Korea4K imputation reference panel, the largest Korean variants reference to date, showed a superior imputation performance to Korea1K across all allele frequency categories. Conclusions Collectively, Korea4K provides not only the largest Korean genome data but also corresponding health check-up parameters and novel genome–phenome associations. The large-scale pathological whole genome–wide omics data will become a powerful set for genome–phenome level association studies to discover causal markers for the prediction and diagnosis of health conditions in future studies.","PeriodicalId":12581,"journal":{"name":"GigaScience","volume":"24 1","pages":""},"PeriodicalIF":9.2,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140614276","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}
Pub Date : 2024-04-04DOI: 10.1093/gigascience/giae011
Mariano Ruz Jurado, Lukas S Tombor, Mani Arsalan, Tomas Holubec, Fabian Emrich, Thomas Walther, Wesley Abplanalp, Ariane Fischer, Andreas M Zeiher, Marcel H Schulz, Stefanie Dimmeler, David John
Background Cardiovascular research heavily relies on mouse (Mus musculus) models to study disease mechanisms and to test novel biomarkers and medications. Yet, applying these results to patients remains a major challenge and often results in noneffective drugs. Therefore, it is an open challenge of translational science to develop models with high similarities and predictive value. This requires a comparison of disease models in mice with diseased tissue derived from humans. Results To compare the transcriptional signatures at single-cell resolution, we implemented an integration pipeline called OrthoIntegrate, which uniquely assigns orthologs and therewith merges single-cell RNA sequencing (scRNA-seq) RNA of different species. The pipeline has been designed to be as easy to use and is fully integrable in the standard Seurat workflow. We applied OrthoIntegrate on scRNA-seq from cardiac tissue of heart failure patients with reduced ejection fraction (HFrEF) and scRNA-seq from the mice after chronic infarction, which is a commonly used mouse model to mimic HFrEF. We discovered shared and distinct regulatory pathways between human HFrEF patients and the corresponding mouse model. Overall, 54% of genes were commonly regulated, including major changes in cardiomyocyte energy metabolism. However, several regulatory pathways (e.g., angiogenesis) were specifically regulated in humans. Conclusions The demonstration of unique pathways occurring in humans indicates limitations on the comparability between mice models and human HFrEF and shows that results from the mice model should be validated carefully. OrthoIntegrate is publicly accessible (https://github.com/MarianoRuzJurado/OrthoIntegrate) and can be used to integrate other large datasets to provide a general comparison of models with patient data.
{"title":"Improved integration of single-cell transcriptome data demonstrates common and unique signatures of heart failure in mice and humans","authors":"Mariano Ruz Jurado, Lukas S Tombor, Mani Arsalan, Tomas Holubec, Fabian Emrich, Thomas Walther, Wesley Abplanalp, Ariane Fischer, Andreas M Zeiher, Marcel H Schulz, Stefanie Dimmeler, David John","doi":"10.1093/gigascience/giae011","DOIUrl":"https://doi.org/10.1093/gigascience/giae011","url":null,"abstract":"Background Cardiovascular research heavily relies on mouse (Mus musculus) models to study disease mechanisms and to test novel biomarkers and medications. Yet, applying these results to patients remains a major challenge and often results in noneffective drugs. Therefore, it is an open challenge of translational science to develop models with high similarities and predictive value. This requires a comparison of disease models in mice with diseased tissue derived from humans. Results To compare the transcriptional signatures at single-cell resolution, we implemented an integration pipeline called OrthoIntegrate, which uniquely assigns orthologs and therewith merges single-cell RNA sequencing (scRNA-seq) RNA of different species. The pipeline has been designed to be as easy to use and is fully integrable in the standard Seurat workflow. We applied OrthoIntegrate on scRNA-seq from cardiac tissue of heart failure patients with reduced ejection fraction (HFrEF) and scRNA-seq from the mice after chronic infarction, which is a commonly used mouse model to mimic HFrEF. We discovered shared and distinct regulatory pathways between human HFrEF patients and the corresponding mouse model. Overall, 54% of genes were commonly regulated, including major changes in cardiomyocyte energy metabolism. However, several regulatory pathways (e.g., angiogenesis) were specifically regulated in humans. Conclusions The demonstration of unique pathways occurring in humans indicates limitations on the comparability between mice models and human HFrEF and shows that results from the mice model should be validated carefully. OrthoIntegrate is publicly accessible (https://github.com/MarianoRuzJurado/OrthoIntegrate) and can be used to integrate other large datasets to provide a general comparison of models with patient data.","PeriodicalId":12581,"journal":{"name":"GigaScience","volume":"103 1","pages":""},"PeriodicalIF":9.2,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140599512","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}
Pub Date : 2024-04-04DOI: 10.1093/gigascience/giae010
Michael B Hall, Lachlan J M Coin
Background Culture-free real-time sequencing of clinical metagenomic samples promises both rapid pathogen detection and antimicrobial resistance profiling. However, this approach introduces the risk of patient DNA leakage. To mitigate this risk, we need near-comprehensive removal of human DNA sequences at the point of sequencing, typically involving the use of resource-constrained devices. Existing benchmarks have largely focused on the use of standardized databases and largely ignored the computational requirements of depletion pipelines as well as the impact of human genome diversity. Results We benchmarked host removal pipelines on simulated and artificial real Illumina and Nanopore metagenomic samples. We found that construction of a custom kraken database containing diverse human genomes results in the best balance of accuracy and computational resource usage. In addition, we benchmarked pipelines using kraken and minimap2 for taxonomic classification of Mycobacterium reads using standard and custom databases. With a database representative of the Mycobacterium genus, both tools obtained improved specificity and sensitivity, compared to the standard databases for classification of Mycobacterium tuberculosis. Computational efficiency of these custom databases was superior to most standard approaches, allowing them to be executed on a laptop device. Conclusions Customized pangenome databases provide the best balance of accuracy and computational efficiency when compared to standard databases for the task of human read removal and M. tuberculosis read classification from metagenomic samples. Such databases allow for execution on a laptop, without sacrificing accuracy, an especially important consideration in low-resource settings. We make all customized databases and pipelines freely available.
背景 临床元基因组样本的无培养基实时测序可实现病原体的快速检测和抗菌药耐药性分析。然而，这种方法会带来病人 DNA 泄漏的风险。为了降低这种风险，我们需要在测序时近乎全面地清除人类 DNA 序列，通常需要使用资源有限的设备。现有的基准主要集中在标准化数据库的使用上，在很大程度上忽略了删除管道的计算要求以及人类基因组多样性的影响。结果 我们在模拟和人工真实 Illumina 和 Nanopore 元基因组样本上对宿主去除管道进行了基准测试。我们发现，构建一个包含不同人类基因组的定制 kraken 数据库，能在准确性和计算资源使用之间取得最佳平衡。此外，我们还利用标准数据库和定制数据库，对使用 kraken 和 minimap2 对分枝杆菌读数进行分类的管道进行了基准测试。与结核分枝杆菌分类的标准数据库相比，使用具有代表性的分枝杆菌属数据库，这两种工具都提高了特异性和灵敏度。这些定制数据库的计算效率优于大多数标准方法，可以在笔记本电脑上执行。结论 与标准数据库相比，定制的泛基因组数据库在从元基因组样本中去除人类读数和进行结核分枝杆菌读数分类时，能在准确性和计算效率之间取得最佳平衡。这样的数据库可以在笔记本电脑上执行，而不会牺牲准确性，这在资源匮乏的环境中是一个特别重要的考虑因素。我们免费提供所有定制的数据库和管道。
{"title":"Pangenome databases improve host removal and mycobacteria classification from clinical metagenomic data","authors":"Michael B Hall, Lachlan J M Coin","doi":"10.1093/gigascience/giae010","DOIUrl":"https://doi.org/10.1093/gigascience/giae010","url":null,"abstract":"Background Culture-free real-time sequencing of clinical metagenomic samples promises both rapid pathogen detection and antimicrobial resistance profiling. However, this approach introduces the risk of patient DNA leakage. To mitigate this risk, we need near-comprehensive removal of human DNA sequences at the point of sequencing, typically involving the use of resource-constrained devices. Existing benchmarks have largely focused on the use of standardized databases and largely ignored the computational requirements of depletion pipelines as well as the impact of human genome diversity. Results We benchmarked host removal pipelines on simulated and artificial real Illumina and Nanopore metagenomic samples. We found that construction of a custom kraken database containing diverse human genomes results in the best balance of accuracy and computational resource usage. In addition, we benchmarked pipelines using kraken and minimap2 for taxonomic classification of Mycobacterium reads using standard and custom databases. With a database representative of the Mycobacterium genus, both tools obtained improved specificity and sensitivity, compared to the standard databases for classification of Mycobacterium tuberculosis. Computational efficiency of these custom databases was superior to most standard approaches, allowing them to be executed on a laptop device. Conclusions Customized pangenome databases provide the best balance of accuracy and computational efficiency when compared to standard databases for the task of human read removal and M. tuberculosis read classification from metagenomic samples. Such databases allow for execution on a laptop, without sacrificing accuracy, an especially important consideration in low-resource settings. We make all customized databases and pipelines freely available.","PeriodicalId":12581,"journal":{"name":"GigaScience","volume":"244 1","pages":""},"PeriodicalIF":9.2,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140599486","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}
Pub Date : 2024-01-10DOI: 10.1093/gigascience/giad115
Anna Niehues, Casper de Visser, Fiona A Hagenbeek, Purva Kulkarni, René Pool, Naama Karu, Alida S D Kindt, Gurnoor Singh, Robert R J M Vermeiren, Dorret I Boomsma, Jenny van Dongen, Peter A C ’t Hoen, Alain J van Gool
Background Applying good data management and FAIR (Findable, Accessible, Interoperable, and Reusable) data principles in research projects can help disentangle knowledge discovery, study result reproducibility, and data reuse in future studies. Based on the concepts of the original FAIR principles for research data, FAIR principles for research software were recently proposed. FAIR Digital Objects enable discovery and reuse of Research Objects, including computational workflows for both humans and machines. Practical examples can help promote the adoption of FAIR practices for computational workflows in the research community. We developed a multi-omics data analysis workflow implementing FAIR practices to share it as a FAIR Digital Object. Findings We conducted a case study investigating shared patterns between multi-omics data and childhood externalizing behavior. The analysis workflow was implemented as a modular pipeline in the workflow manager Nextflow, including containers with software dependencies. We adhered to software development practices like version control, documentation, and licensing. Finally, the workflow was described with rich semantic metadata, packaged as a Research Object Crate, and shared via WorkflowHub. Conclusions Along with the packaged multi-omics data analysis workflow, we share our experiences adopting various FAIR practices and creating a FAIR Digital Object. We hope our experiences can help other researchers who develop omics data analysis workflows to turn FAIR principles into practice.
{"title":"A multi-omics data analysis workflow packaged as a FAIR Digital Object","authors":"Anna Niehues, Casper de Visser, Fiona A Hagenbeek, Purva Kulkarni, René Pool, Naama Karu, Alida S D Kindt, Gurnoor Singh, Robert R J M Vermeiren, Dorret I Boomsma, Jenny van Dongen, Peter A C ’t Hoen, Alain J van Gool","doi":"10.1093/gigascience/giad115","DOIUrl":"https://doi.org/10.1093/gigascience/giad115","url":null,"abstract":"Background Applying good data management and FAIR (Findable, Accessible, Interoperable, and Reusable) data principles in research projects can help disentangle knowledge discovery, study result reproducibility, and data reuse in future studies. Based on the concepts of the original FAIR principles for research data, FAIR principles for research software were recently proposed. FAIR Digital Objects enable discovery and reuse of Research Objects, including computational workflows for both humans and machines. Practical examples can help promote the adoption of FAIR practices for computational workflows in the research community. We developed a multi-omics data analysis workflow implementing FAIR practices to share it as a FAIR Digital Object. Findings We conducted a case study investigating shared patterns between multi-omics data and childhood externalizing behavior. The analysis workflow was implemented as a modular pipeline in the workflow manager Nextflow, including containers with software dependencies. We adhered to software development practices like version control, documentation, and licensing. Finally, the workflow was described with rich semantic metadata, packaged as a Research Object Crate, and shared via WorkflowHub. Conclusions Along with the packaged multi-omics data analysis workflow, we share our experiences adopting various FAIR practices and creating a FAIR Digital Object. We hope our experiences can help other researchers who develop omics data analysis workflows to turn FAIR principles into practice.","PeriodicalId":12581,"journal":{"name":"GigaScience","volume":"8 1","pages":""},"PeriodicalIF":9.2,"publicationDate":"2024-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139463300","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}
Pub Date : 2024-01-02DOI: 10.1093/gigascience/giae053
Paulene S Pineda, Ester B Flores, Lilian P Villamor, Connie Joyce M Parac, Mehar S Khatkar, Hien To Thu, Timothy P L Smith, Benjamin D Rosen, Paolo Ajmone-Marsan, Licia Colli, John L Williams, Wai Yee Low
More people in the world depend on water buffalo for their livelihoods than on any other domesticated animals, but its genetics is still not extensively explored. The 1000 Buffalo Genomes Project (1000BGP) provides genetic resources for global buffalo population study and tools to breed more sustainable and productive buffaloes. Here we report the most contiguous swamp buffalo genome assembly (PCC_UOA_SB_1v2) with substantial resolution of telomeric and centromeric repeats, ∼4-fold more contiguous than the existing reference river buffalo assembly and exceeding a recently published male swamp buffalo genome. This assembly was used along with the current reference to align 140 water buffalo short-read sequences and produce a public genetic resource with an average of ∼41 million single nucleotide polymorphisms per swamp and river buffalo genome. Comparison of the swamp and river buffalo sequences showed ∼1.5% genetic differences, and estimated divergence time occurred 3.1 million years ago (95% CI, 2.6-4.9). The open science model employed in the 1000BGP provides a key genomic resource and tools for a species with global economic relevance.
{"title":"Disentangling river and swamp buffalo genetic diversity: initial insights from the 1000 Buffalo Genomes Project.","authors":"Paulene S Pineda, Ester B Flores, Lilian P Villamor, Connie Joyce M Parac, Mehar S Khatkar, Hien To Thu, Timothy P L Smith, Benjamin D Rosen, Paolo Ajmone-Marsan, Licia Colli, John L Williams, Wai Yee Low","doi":"10.1093/gigascience/giae053","DOIUrl":"10.1093/gigascience/giae053","url":null,"abstract":"<p><p>More people in the world depend on water buffalo for their livelihoods than on any other domesticated animals, but its genetics is still not extensively explored. The 1000 Buffalo Genomes Project (1000BGP) provides genetic resources for global buffalo population study and tools to breed more sustainable and productive buffaloes. Here we report the most contiguous swamp buffalo genome assembly (PCC_UOA_SB_1v2) with substantial resolution of telomeric and centromeric repeats, ∼4-fold more contiguous than the existing reference river buffalo assembly and exceeding a recently published male swamp buffalo genome. This assembly was used along with the current reference to align 140 water buffalo short-read sequences and produce a public genetic resource with an average of ∼41 million single nucleotide polymorphisms per swamp and river buffalo genome. Comparison of the swamp and river buffalo sequences showed ∼1.5% genetic differences, and estimated divergence time occurred 3.1 million years ago (95% CI, 2.6-4.9). The open science model employed in the 1000BGP provides a key genomic resource and tools for a species with global economic relevance.</p>","PeriodicalId":12581,"journal":{"name":"GigaScience","volume":"13 ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11382405/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-02DOI: 10.1093/gigascience/giae079
Niklas Birth, Nicolina Leppich, Julia Schirmacher, Nina Andreae, Rasmus Steinkamp, Matthias Blanke, Peter Meinicke
Background: The exploration of the microbial world has been greatly advanced by the reconstruction of genomes from metagenomic sequence data. However, the rapidly increasing number of metagenome-assembled genomes has also resulted in a wide variation in data quality. It is therefore essential to quantify the achieved completeness and possible contamination of a reconstructed genome before it is used in subsequent analyses. The classical approach for the estimation of quality indices solely relies on a relatively small number of universal single-copy genes. Recent tools try to extend the genomic coverage of estimates for an increased accuracy.
Results: We developed CoCoPyE, a fast tool based on a novel 2-stage feature extraction and transformation scheme. First, it identifies genomic markers and then refines the marker-based estimates with a machine learning approach. In our simulation studies, CoCoPyE showed a more accurate prediction of quality indices than the existing tools. While the CoCoPyE web server offers an easy way to try out the tool, the freely available Python implementation enables integration into existing genome reconstruction pipelines.
Conclusions: CoCoPyE provides a new approach to assess the quality of genome data. It complements and improves existing tools and may help researchers to better distinguish between low-quality draft and high-quality genome assemblies in metagenome sequencing projects.
{"title":"CoCoPyE: feature engineering for learning and prediction of genome quality indices.","authors":"Niklas Birth, Nicolina Leppich, Julia Schirmacher, Nina Andreae, Rasmus Steinkamp, Matthias Blanke, Peter Meinicke","doi":"10.1093/gigascience/giae079","DOIUrl":"https://doi.org/10.1093/gigascience/giae079","url":null,"abstract":"<p><strong>Background: </strong>The exploration of the microbial world has been greatly advanced by the reconstruction of genomes from metagenomic sequence data. However, the rapidly increasing number of metagenome-assembled genomes has also resulted in a wide variation in data quality. It is therefore essential to quantify the achieved completeness and possible contamination of a reconstructed genome before it is used in subsequent analyses. The classical approach for the estimation of quality indices solely relies on a relatively small number of universal single-copy genes. Recent tools try to extend the genomic coverage of estimates for an increased accuracy.</p><p><strong>Results: </strong>We developed CoCoPyE, a fast tool based on a novel 2-stage feature extraction and transformation scheme. First, it identifies genomic markers and then refines the marker-based estimates with a machine learning approach. In our simulation studies, CoCoPyE showed a more accurate prediction of quality indices than the existing tools. While the CoCoPyE web server offers an easy way to try out the tool, the freely available Python implementation enables integration into existing genome reconstruction pipelines.</p><p><strong>Conclusions: </strong>CoCoPyE provides a new approach to assess the quality of genome data. It complements and improves existing tools and may help researchers to better distinguish between low-quality draft and high-quality genome assemblies in metagenome sequencing projects.</p>","PeriodicalId":12581,"journal":{"name":"GigaScience","volume":"13 ","pages":""},"PeriodicalIF":11.8,"publicationDate":"2024-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11503480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142498590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In classic semiquantitative metabolomics, metabolite intensities are affected by biological factors and other unwanted variations. A systematic evaluation of the data processing methods is crucial to identify adequate processing procedures for a given experimental setup. Current comparative studies are mostly focused on peak area data but not on absolute concentrations. In this study, we evaluated data processing methods to produce outputs that were most similar to the corresponding absolute quantified data. We examined the data distribution characteristics, fold difference patterns between 2 metabolites, and sample variance. We used 2 metabolomic datasets from a retail milk study and a lupus nephritis cohort as test cases. When studying the impact of data normalization, transformation, scaling, and combinations of these methods, we found that the cross-contribution compensating multiple standard normalization (ccmn) method, followed by square root data transformation, was most appropriate for a well-controlled study such as the milk study dataset. Regarding the lupus nephritis cohort study, only ccmn normalization could slightly improve the data quality of the noisy cohort. Since the assessment accounted for the resemblance between processed data and the corresponding absolute quantified data, our results denote a helpful guideline for processing metabolomic datasets within a similar context (food and clinical metabolomics). Finally, we introduce Metabox 2.0, which enables thorough analysis of metabolomic data, including data processing, biomarker analysis, integrative analysis, and data interpretation. It was successfully used to process and analyze the data in this study. An online web version is available at http://metsysbio.com/metabox.
{"title":"Data processing solutions to render metabolomics more quantitative: case studies in food and clinical metabolomics using Metabox 2.0.","authors":"Kwanjeera Wanichthanarak, Ammarin In-On, Sili Fan, Oliver Fiehn, Arporn Wangwiwatsin, Sakda Khoomrung","doi":"10.1093/gigascience/giae005","DOIUrl":"10.1093/gigascience/giae005","url":null,"abstract":"<p><p>In classic semiquantitative metabolomics, metabolite intensities are affected by biological factors and other unwanted variations. A systematic evaluation of the data processing methods is crucial to identify adequate processing procedures for a given experimental setup. Current comparative studies are mostly focused on peak area data but not on absolute concentrations. In this study, we evaluated data processing methods to produce outputs that were most similar to the corresponding absolute quantified data. We examined the data distribution characteristics, fold difference patterns between 2 metabolites, and sample variance. We used 2 metabolomic datasets from a retail milk study and a lupus nephritis cohort as test cases. When studying the impact of data normalization, transformation, scaling, and combinations of these methods, we found that the cross-contribution compensating multiple standard normalization (ccmn) method, followed by square root data transformation, was most appropriate for a well-controlled study such as the milk study dataset. Regarding the lupus nephritis cohort study, only ccmn normalization could slightly improve the data quality of the noisy cohort. Since the assessment accounted for the resemblance between processed data and the corresponding absolute quantified data, our results denote a helpful guideline for processing metabolomic datasets within a similar context (food and clinical metabolomics). Finally, we introduce Metabox 2.0, which enables thorough analysis of metabolomic data, including data processing, biomarker analysis, integrative analysis, and data interpretation. It was successfully used to process and analyze the data in this study. An online web version is available at http://metsysbio.com/metabox.</p>","PeriodicalId":12581,"journal":{"name":"GigaScience","volume":"13 ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10941642/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140131178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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