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基因组蛋白质组与生物信息学报（英文版）
基因组蛋白质组与生物信息学报（英文版）

杨焕明；于军

双月刊

1672-0229

journal@cspg.net

010-84097425

100101

北京市朝阳区北辰西路1-7号中国科学院北京基因组研究所

基因组蛋白质组与生物信息学报（英文版）/Journal Genomics、Proteomics & BioinformaticsCSCDCSTPCD北大核心SCI
查看更多>>Genomics, Proteomics & Bioinformatics (《基因组蛋白质组与生物信息学报》，简称GPB)创刊于2003年，是由中国科学院北京基因组研究所主办、科学出版社出版的国家级英文学术期刊，由杨焕明教授、于军教授担任主编，汪建教授、贺福初院士担任副主编。 本刊主要刊载基因组学、蛋白质组学、生物信息学及其相关领域的研究进展、综述、研究论文、实验技术与方法、研究快讯等高质量的稿件，突出刊物的学术性、前沿性、指导性和实用性。 本刊读者对象为基础医学、生命科学、农学、计算机科学领域的科研与教学人员、研究生等，以及数学、物理学领域对生物科学有兴趣的研究者。 GPB (ISSN 1672-0229，CN11-4926/Q)现为季刊，面向国内外发行，邮发代号80-113。2004年国内定价每期45元，全年180元。 欢迎赐稿和订阅! 联系人：张欣 《基因组蛋白质组与生物信息学报》编辑部 北京空港科技创业园B区6号 101300 Tel: 010-80485179 Fax: 010-80498676 E-mail：editor@genomics.org.cn Http：
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    T2T-YAO,T2T-SHUN,and more

    Jingfa XiaoJun Yu
    1081-1082页
      原文链接:
    • NETL
    • NSTL
    • 万方数据

    T2T-YAO Reference Genome of Han Chinese—New Step in Advancing Precision Medicine in China

    Xue Zhang
    1083-1084页
      原文链接:
    • NETL
    • NSTL
    • 万方数据

    T2T-YAO:A Telomere-to-telomere Assembled Diploid Reference Genome for Han Chinese

    Yukun HeYanan ChuShuming GuoJiang Hu...
    1085-1100页
    查看更多>>摘要：Since its initial release in 2001,the human reference genome has undergone continuous improvement in quality,and the recently released telomere-to-telomere(T2T)version-T2T-CHM13-reaches its highest level of continuity and accuracy after 20 years of effort by working on a simplified,nearly homozygous genome of a hydatidiform mole cell line.Here,to provide an authentic complete diploid human genome reference for the Han Chinese,the largest population in the world,we assembled the genome of a male Han Chinese individual,T2T-YAO,which includes T2T assemblies of all the 22+X+M and 22+Y chromosomes in both haploid.The quality of T2T-YAO is much better than all currently available diploid assemblies,and its hap-loid version,T2T-YAO-hp,generated by selecting the better assembly for each autosome,reaches the top quality of fewer than one error per 29.5 Mb,even higher than that of T2T-CHM13.Derived from an individual living in the aboriginal region of the Han population,T2T-YAO shows clear ancestry and potential genetic continuity from the ancient ancestors.Each haplotype of T2T-YAO possesses～330-Mb exclusive sequences,～3100 unique genes,and tens of thousands of nucleotide and structural variations as compared with CHM13,highlighting the necessity of a population-stratified reference genome.The construction of T2T-YAO,a truly accurate and authentic representative of the Chinese population,would enable precise delineation of genomic variations and advance our understandings in the hereditability of diseases and phenotypes,espe-cially within the context of the unique variations of the Chinese population.
      原文链接:
    • NETL
    • NSTL
    • 万方数据

    Novel Time-dependent Multi-omics Integration in Sepsis-associated Liver Dysfunction

    Ann-Yae NaHyojin LeeEun Ki MinSanjita Paudel...
    1101-1116页
    查看更多>>摘要：The recently developed technologies that allow the analysis of each single omics have provided an unbiased insight into ongoing disease processes.However,it remains challenging to specify the study design for the subsequent integration strategies that can associate sepsis patho-physiology and clinical outcomes.Here,we conducted a time-dependent multi-omics integration(TDMI)in a sepsis-associated liver dysfunction(SALD)model.We successfully deduced the relation of the toll-like receptor 4(TLR4)pathway with SALD.Although TLR4 is a critical factor in sepsis progression,it is not specified in single-omics results but only in the TDMI analysis.This result indi-cates that the TDMI-based approach is more advantageous than single-omics analysis in terms of exploring the underlying pathophysiological mechanism of this disease.Furthermore,this approach can be an ideal paradigm for insightful biological interpretations of multi-omics datasets that will potentially reveal novel insights into basic biology,health,and diseases,thus allowing the identifi-cation of promising candidates for therapeutic strategies.
      原文链接:
    • NETL
    • NSTL
    • 万方数据

    Comprehensive Characterization and Global Transcriptome Analysis of Human Fetal Liver Terminal Erythropoiesis

    Yongshuai HanShihui WangYaomei WangYumin Huang...
    1117-1132页
    查看更多>>摘要：The fetal liver(FL)is the key erythropoietic organ during fetal development,but knowl-edge on human FL erythropoiesis is very limited.In this study,we sorted primary erythroblasts from FL cells and performed RNA sequencing(RNA-seq)analyses.We found that temporal gene expression patterns reflected changes in function during primary human FL terminal erythropoiesis.Notably,the expression of genes enriched in proteolysis and autophagy was up-regulated in orthochromatic erythroblasts(OrthoEs),suggesting the involvement of these pathways in enucle-ation.We also performed RNA-seq of in vitro cultured erythroblasts derived from FL CD34+cells.Comparison of transcriptomes between the primary and cultured erythroblasts revealed significant differences,indicating impacts of the culture system on gene expression.Notably,the expression of lipid metabolism-related genes was increased in cultured erythroblasts.We further immortalized ery-throid cell lines from FL and cord blood(CB)CD34+cells(FL-iEry and CB-iEry,respectively).FL-iEry and CB-iEry were immortalized at the proerythroblast stage and can be induced to differ-entiate into OrthoEs,but their enucleation ability was very low.Comparison of the transcriptomes between OrthoEs with and without enucleation capability revealed the down-regulation of path-ways involved in chromatin organization and mitophagy in OrthoEs without enucleation capacity,indicating that defects in chromatin organization and mitophagy contribute to the inability of OrthoEs to enucleate.Additionally,the expression of HBE1,HBZ,and HBG2 was up-regulated in FL-iEry compared with CB-iEry,and this up-regulation was accompanied by down-regulated expression of BCL11A and up-regulated expression of LIN28B and IGF2BP1.Our study provides new insights into human FL erythropoiesis and rich resources for future studies.
      原文链接:
    • NETL
    • NSTL
    • 万方数据

    Acid-base Homeostasis and Implications to the Phenotypic Behaviors of Cancer

    Yi ZhouWennan ChangXiaoyu LuJin Wang...
    1133-1148页
    查看更多>>摘要：Acid-base homeostasis is a fundamental property of living cells,and its persistent disrup-tion in human cells can lead to a wide range of diseases.In this study,we conducted a computa-tional modeling analysis of transcriptomic data of 4750 human tissue samples of 9 cancer types in The Cancer Genome Atlas(TCGA)database.Built on our previous study,we quantitatively esti-mated the average production rate of OH-by cytosolic Fenton reactions,which continuously dis-rupt the intracellular pH(pHi)homeostasis.Our predictions indicate that all or at least a subset of 43 reprogrammed metabolisms(RMs)are induced to produce net protons(H+)at comparable rates of Fenton reactions to keep the pHi stable.We then discovered that a number of well-known phenotypes of cancers,including increased growth rate,metastasis rate,and local immune cell composition,can be naturally explained in terms of the Fenton reaction level and the induced RMs.This study strongly suggests the possibility to have a unified framework for studies of cancer-inducing stressors,adaptive metabolic reprogramming,and cancerous behaviors.In addition,strong evidence is provided to demonstrate that a popular view that Na+/H+exchangers along with lactic acid exporters and carbonic anhydrases are responsible for the intracellular alkalization and extra-cellular acidification in cancer may not be justified.
      原文链接:
    • NETL
    • NSTL
    • 万方数据

    Multi-omics Data Reveal the Effect of Sodium Butyrate on Gene Expression and Protein Modification in Streptomyces

    Jiazhen ZhengYue LiNing LiuJihui Zhang...
    1149-1162页
    查看更多>>摘要：Streptomycetes possess numerous gene clusters and the potential to produce a large amount of natural products.Histone deacetylase(HDAC)inhibitors play an important role in the regulation of histone modifications in fungi,but their roles in prokaryotes remain poorly under-stood.Here,we investigated the global effects of the HDAC inhibitor,sodium butyrate(SB),on marine-derived Streptomyces olivaceus FXJ 8.021,particularly focusing on the activation of secondary metabolite biosynthesis.The antiSMASH analysis revealed 33 secondary metabolite biosynthetic gene clusters(BGCs)in strain FXJ 8.021,among which the silent lobophorin BGC was activated by SB.Transcriptomic data showed that the expression of genes involved in lobo-phorin biosynthesis(ge00097-ge00139)and CoA-ester formation(e.g.,ge02824),as well as the gly-colysis/gluconeogenesis pathway(e.g.,ge01661),was significantly up-regulated in the presence of SB.Intracellular CoA-ester analysis confirmed that SB triggered the biosynthesis of CoA-ester,thereby increasing the precursor supply for lobophorin biosynthesis.Further acetylomic analysis revealed that the acetylation levels on 218 sites of 190 proteins were up-regulated and those on 411 sites of 310 proteins were down-regulated.These acetylated proteins were particularly enriched in transcriptional and translational machinery components(e.g.,elongation factor GE04399),and their correlations with the proteins involved in lobophorin biosynthesis were established by protein-protein interaction network analysis,suggesting that SB might function via a complex hierarchical regulation to activate the expression of lobophorin BGC.These findings provide solid evidence that acetylated proteins triggered by SB could affect the expression of genes involved in the biosynthesis of primary and secondary metabolites in prokaryotes.
      原文链接:
    • NETL
    • NSTL
    • 万方数据

    Protein Lactylation and Metabolic Regulation of the Zoonotic Parasite Toxoplasma gondii

    Deqi YinNing JiangChang ChengXiaoyu Sang...
    1163-1181页
    查看更多>>摘要：The biology of Toxoplasma gondii,the causative pathogen of one of the most widespread parasitic diseases(toxoplasmosis),remains poorly understood.Lactate,which is derived from glu-cose metabolism,is not only an energy source in a variety of organisms,including T.gondii,but also a regulatory molecule that participates in gene activation and protein function.Lysine lactylation(Kla)is a type of post-translational modifications(PTMs)that has been recently associated with chromatin remodeling;however,K1a of histone and non-histone proteins has not yet been studied in T.gondii.To examine the prevalence and function of lactylation in T.gondii parasites,we mapped the lactylome of proliferating tachyzoite cells and identified 1964 K1a sites on 955 proteins in the T.gondii RH strain.Lactylated proteins were distributed in multiple subcellular compart-ments and were closely related to a wide variety of biological processes,including mRNA splicing,glycolysis,aminoacyl-tRNA biosynthesis,RNA transport,and many signaling pathways.We also performed a chromatin immunoprecipitation sequencing(ChIP-seq)analysis using a lactylation-specific antibody and found that the histones H4K121a and H3K141a were enriched in the promoter and exon regions of T.gondii associated with microtubule-based movement and cell invasion.We further confirmed the delactylase activity of histone deacetylases TgHDAC2-4,and found that treatment with anti-histone acetyltransferase(TgMYST-A)antibodies profoundly reduced protein lactylation in T.gondii.This study offers the first dataset of the global lactylation proteome and provides a basis for further dissecting the functional biology of T.gondii.
      原文链接:
    • NETL
    • NSTL
    • 万方数据

    Sequence-based Functional Metagenomics Reveals Novel Natural Diversity of Functional Cop A in Environmental Microbiomes

    Wenjun LiLikun WangXiaofang LiXin Zheng...
    1182-1194页
    查看更多>>摘要：Exploring the natural diversity of functional genes/proteins from environmental DNA in high-throughput remains challenging.In this study,we developed a sequence-based functional metagenomics procedure for mining the diversity of copper(Cu)resistance gene copA in global microbiomes,by combining the metagenomic assembly technology,local BLAST,evolutionary trace analysis(ETA),chemical synthesis,and conventional functional genomics.In total,87 meta-genomes were collected from a public database and subjected to copA detection,resulting in 93,899 hits.Manual curation of 1214 hits of high confidence led to the retrieval of 517 unique CopA can-didates,which were further subjected to ETA.Eventually,175 novel copA sequences of high quality were discovered.Phylogenetic analysis showed that almost all these putative CopA proteins were distantly related to known CopA proteins,with 55 sequences from totally unknown species.Ten novel and three known copA genes were chemically synthesized for further functional genomic tests using the Cu-sensitive Escherichia coli(ΔcopA).The growth test and Cu uptake determination showed that five novel clones had positive effects on host Cu resistance and uptake.One recombi-nant harboring copA-like 15(copAL15)successfully restored Cu resistance of the host with a sub-stantially enhanced Cu uptake.Two novel copA genes were fused with the gfp gene and expressed in E.coli for microscopic observation.Imaging results showed that they were successfully expressed and their proteins were localized to the membrane.The results here greatly expand the diversity of known CopA proteins,and the sequence-based procedure developed overcomes biases in length,screening methods,and abundance of conventional functional metagenomics.
      原文链接:
    • NETL
    • NSTL
    • 万方数据

    High Sensitivity of Shotgun Metagenomic Sequencing in Colon Tissue Biopsy by Host DNA Depletion

    Wing Yin ChengWei-Xin LiuYanqiang DingGuoping Wang...
    1195-1205页
    查看更多>>摘要：The high host genetic background of tissue biopsies hinders the application of shotgun metagenomic sequencing in characterizing the tissue microbiota.We proposed an optimized method that removed host DNA from colon biopsies and examined the effect on metagenomic analysis.Human or mouse colon biopsies were divided into two groups,with one group undergoing host DNA depletion and the other serving as the control.Host DNAs were removed through differential lysis of mammalian and bacterial cells before sequencing.The impact of host DNA depletion on microbiota was compared based on phylogenetic diversity analyses and regression analyses.Removing host DNA enhanced bacterial sequencing depth and improved species discovery,increas-ing bacterial reads by 2.46±0.20 fold while reducing host reads by 6.80％±1.06％.Moreover,3.40 times more of bacterial species were detected after host DNA depletion.This was confirmed from mouse colon tissues,increasing bacterial reads by 5.46±0.42 fold while decreasing host reads by 10.2％±0.83％.Similarly,significantly more species were detected in the mouse colon tissue upon host DNA depletion(P＜0.001).Furthermore,an increased microbial richness was evident in the host DNA-depleted samples compared with non-depleted controls in human colon biopsies and mouse colon tissues(P＜0.001).Our optimized method of host DNA depletion improved the sensitivity of shotgun metagenomic sequencing in bacterial detection in the biopsy,which may yield a more accurate taxonomic profile of the tissue microbiota and identify bacteria that are important for disease initiation or progression.
      原文链接:
    • NETL
    • NSTL
    • 万方数据