中国人群参考基因组及基因组变异图谱资源库

随着人类基因组计划和国际千人基因组计划的实施,已公开数百个中国人个体的全基因组数据。建立高精度的中国人群参考基因组序列,发现并解析中国人群特有的序列变异,是我国未来精准医学研究的基础。为满足未来精准医学研究中国人基因组数据持续增长的科学管理和深入研究的需求,中国科学院北京基因组研究所发展并建立了基于中国人群全基因组测序数据的虚拟中国人基因组数据库(Virtual Chinese Genome Database,VCGDB)和中国人群基因组变异数据库(Genome Variation Map, GVM),面向国内外用户提供数据检索、共享、下载和在线分析服务。本文重点介绍了这两个数据库的特点和功能,以及未来发展与应用前景,以期为中国人群参考基因组及基因组变异图谱资源库的推广使用、发展完善提供有益信息。

生命与健康大数据中心资源

生命与健康多组学数据是生命科学研究和生物医学技术发展的重要基础。然而,我国缺乏生物数据管理和共享平台,不但无法满足国内日益增长的生物医学及相关学科领域的研究发展需求,而且严重制约我国生物大数据整合共享与转化利用。鉴于此,中国科学院北京基因组研究所于2016年初成立生命与健康大数据中心(BIG Data Center,BIGD),围绕国家人口健康和重要战略生物资源,建立生物大数据管理平台和多组学数据资源体系。本文重点介绍BIGD的生命与健康大数据资源系统,主要包括组学原始数据归档库、基因组数据库、基因组变异数据库、基因表达数据库、甲基化数据库、生物信息工具库和生命科学维基知识库,提供生物大数据汇交、整合与共享服务,为促进我国生命科学数据管理、推动国家生物信息中心建设奠定重要基础。

The Global Landscape of SARS-CoV-2 Genomes, Variants, and Haplotypes in 2019nCoVR

On January 22,2020,China National Center for Bioinformation(CNCB)released the 2019 Novel Coronavirus Resource(2019nCoVR),an open-access information resource for the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).2019nCoVR features a comprehensive integration of sequence and clinical information for all publicly available SARS-CoV-2 isolates,which are manually curated with value-added annotations and quality evaluated by an automated in-house pipeline.Of particular note,2019nCoVR offers systematic analyses to generate a dynamic landscape of SARS-CoV-2 genomic variations at a global scale.It provides all identified variants and their detailed statistics for each virus isolate,and congregates the quality score,functional annotation,and population frequency for each variant.Spatiotemporal change for each variant can be visualized and historical viral haplotype network maps for the course of the outbreak are also generated based on all complete and high-quality genomes available.Moreover,2019nCoVR provides a full collection of SARS-CoV-2 relevant literature on the coronavirus disease 2019(COVID-19),including published papers from PubMed as well as preprints from services such as bioRxiv and medRxiv through Europe PMC.Furthermore,by linking with relevant databases in CNCB,2019nCoVR offers data submission services for raw sequence reads and assembled genomes,and data sharing with NCBI.Collectively,SARS-CoV-2 is updated daily to collect the latest information on genome sequences,variants,haplotypes,and literature for a timely reflection,making 2019nCoVR a valuable resource for the global research community.2019nCoVR is accessible at https://bigd.big.ac.cn/ncov/.

Compositional Variability and Mutation Spectra of Monophyletic SARS-CoV-2 Clades

COVID-19 and its causative pathogen SARS-CoV-2 have rushed the world into a staggering pandemic in a few months,and a global fight against both has been intensifying.Here,we describe an analysis procedure where genome composition and its variables are related,through the genetic code to molecular mechanisms,based on understanding of RNA replication and its feedback loop from mutation to viral proteome sequence fraternity including effective sites on the replicase-transcriptase complex.Our analysis starts with primary sequence information,identity-based phylogeny based on 22,051 SARS-CoV-2 sequences,and evaluation of sequence variation patterns as mutation spectra and its 12 permutations among organized clades.All are tailored to two key mechanisms:strand-biased and function-associated mutations.Our findings are listed as follows:1)The most dominant mutation is C-to-U permutation,whose abundant second-codon-position counts alter amino acid composition toward higher molecular weight and lower hydrophobicity,albeit assumed most slightly deleterious.2)The second abundance group includes three negative-strand mutations(U-to-C,A-to-G,and G-to-A)and a positive-strand mutation(G-to-U)due to DNA repair mechanisms after cellular abasic events.3)A clade-associated biased mutation trend is found attributable to elevated level of negative-sense strand synthesis.4)Within-clade permutation variation is very informative for associating non-synonymous mutations and viral proteome changes.These findings demand a platform where emerging mutations are mapped onto mostly subtle but fast-adjusting viral proteomes and transcriptomes,to provide biological and clinical information after logical convergence for effective pharmaceutical and diagnostic applications.Such actions are in desperate need,especially in the middle of the War against COVID-19.