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multi-omics analysis of attenuated variant reveals potential evaluation marker of host damaging for SARS-CoV-2 variants

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Science China(Life Sciences) 2024年第1期67卷 83-95页

作者： Guangshan Xie Lin Zhu Siwen Liu Cun Li Xin Diao Yanhao Zhang Xiuli Su Yuanyuan Song Guodong Cao Li Zhong Pui Wang Xiaojuan Liu Bobo Wing-Yee Mok Shusheng Zhang Dong-Yan Jin Jie Zhou Honglin Chen Zongwei Cai State Key Laboratory of Environmental and Biological Analysis Hong Kong Baptist UniversityHong Kong SARChina State Key Laboratory for Emerging Infectious Diseases and Department of MicrobiologyLi Ka Shing Faculty of MedicineThe University of Hong KongHong Kong SARChina College of Chemistry Zhengzhou UniversityZhengzhou 450001China School of Biomedical Sciences The University of Hong KongHong Kong SARChina HKBU Shenzhen Institute of Research and Continuing Education Shenzhen 518000China

SARS-CoV-2 continues to threaten human society by generating novel variants via mutation and recombination.The high number of mutations that appeared in emerging variants not only enhanced their immune-escaping ability but also made it difficult to predict the pathogenicity and virulence based on viral nucleotide sequences.Molecular markers for evaluating the pathogenicity of new variants are therefore needed.By comparing host responses to wild-type and variants with attenuated pathogenicity at proteome and metabolome levels,six key molecules on the polyamine biosynthesis pathway including putrescine,SAM,dc-SAM,ODC1,SAMS,and SAMDC were found to be differentially upregulated and associated with pathogenicity of variants.To validate our discovery,human airway organoids were subsequently used which recapitulates SARS-CoV-2 replication in the airway epithelial cells of COVID-19 patients.Using ODC1 as a proof-ofconcept,differential activation of polyamine biosynthesis was found to be modulated by the renin-angiotensin system(RAS)and positively associated with ACE2 activity.Further experiments demonstrated that ODC1 expression could be differentially activated upon a panel of SARS-CoV-2 variants of concern(VOCs)and was found to be correlated with each VOCs’pathogenic properties.Particularly,the presented study revealed the discriminative ability of key molecules on polyamine biosynthesis as a predictive marker for virulence evaluation and assessment of SARS-CoV-2 variants in cell or organoid models.Our work,therefore,presented a practical strategy that could be potentially applied as an evaluation tool for the pathogenicity of current and emerging SARS-CoV-2 variants.

关键词： SARS-CoV-2 multi-omics attenuated variant predictive pathogenic marker polyamine biosynthesis

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Deciphering gastric inflammation-induced tumorigenesis through multi-omics data and AI methods

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Cancer Biology & Medicine 2024年第4期21卷 312-330页

作者： Qian Zhang Mingran Yang Peng Zhang Bowen Wu Xiaosen Wei Shao Li Institute for TCM-X MOE Key Laboratory of BioinformaticsBioinformatics DivisionBNRISTDepartment of AutomationTsinghua UniversityBeijing 100084China

Gastric cancer(GC), the fifth most common cancer globally, remains the leading cause of cancer deaths worldwide. Inflammation-induced tumorigenesis is the predominant process in GC development;therefore, systematic research in this area should improve understanding of the biological mechanisms that initiate GC development and promote cancer hallmarks. Here, we summarize biological knowledge regarding gastric inflammation-induced tumorigenesis, and characterize the multi-omics data and systems biology methods for investigating GC development. Of note, we highlight pioneering studies in multi-omics data and state-of-the-art network-based algorithms used for dissecting the features of gastric inflammation-induced tumorigenesis, and we propose translational applications in early GC warning biomarkers and precise treatment strategies. This review offers integrative insights for GC research, with the goal of paving the way to novel paradigms for GC precision oncology and prevention.

关键词： Gastric cancer inflammation-induced tumorigenesis multi-omics artificial intelligence network-based methods

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Prioritization of risk genes in colorectal cancer by integrative analysis of multi-omics data and gene networks

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Science China(Life Sciences) 2024年第1期67卷 132-148页

作者： Ming Zhang Xiaoyang Wang Nan Yang Xu Zhu Zequn Lu Yimin Cai Bin Li Ying Zhu Xiangpan Li Yongchang Wei Shaokai Zhang Jianbo Tian Xiaoping Miao Department of Epidemiology and Biostatistics School of Public HealthDepartment of Gastrointestinal OncologyZhongnan Hospital of Wuhan UniversityDepartment of Radiation OncologyRenmin Hospital of Wuhan UniversityTaiKang Center for Life and Medical SciencesWuhan UniversityWuhan 430071China Research Center of Public Health Renmin hospital of Wuhan UniversityWuhan UniversityWuhan 430060China Department of Cancer Epidemiology The Affiliated Cancer Hospital of Zhengzhou University&Henan Cancer HospitalHenan Engineering Research Center of Cancer Prevention and ControlHenan International Joint Laboratory of Cancer PreventionZhengzhou 450008China Department of Gastrointestinal Surgery Renmin Hospital of Wuhan UniversityWuhan 430060China Department of Radiation Oncology Renmin Hospital of Wuhan UniversityWuhan 430060China Department of Gastrointestinal Oncology Hubei Cancer Clinical Study CenterZhongnan Hospital of Wuhan UniversityWuhan 430062China Department of Epidemiology and Biostatistics School of Public HealthTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430073China Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine Nanjing Medical UniversityNanjing 211166China

Genome-wide association studies(GWASs)have identified over 140 colorectal cancer(CRC)-associated loci;however,target genes at the majority of loci and underlying molecular mechanisms are poorly understood.Here,we utilized a Bayesian approach,integrative risk gene selector(iRIGS),to prioritize risk genes at CRC GWAS loci by integrating multi-omics data.As a result,a total of 105 high-confidence risk genes(HRGs)were identified,which exhibited strong gene dependencies for CRC and enrichment in the biological processes implicated in CRC.Among the 105 HRGs,CEBPB,located at the 20q13.13 locus,acted as a transcription factor playing critical roles in cancer.Our subsequent assays indicated the tumor promoter function of CEBPB that facilitated CRC cell proliferation by regulating multiple oncogenic pathways such as MAPK,PI3K-Akt,and Ras signaling.Next,by integrating a fine-mapping analysis and three independent case-control studies in Chinese populations consisting of 8,039 cases and 12,775 controls,we elucidated that rs1810503,a putative functional variant regulating CEBPB,was associated with CRC risk(OR=0.90,95%CI=0.86–0.93,P=1.07×10^(−7)).The association between rs1810503 and CRC risk was further validated in three additional multi-ancestry populations consisting of 24,254 cases and 58,741 controls.Mechanistically,the rs1810503 A to T allele change weakened the enhancer activity in an allele-specific manner to decrease CEBPB expression via longrange promoter-enhancer interactions,mediated by the transcription factor,REST,and thus decreased CRC risk.In summary,our study provides a genetic resource and a generalizable strategy for CRC etiology investigation,and highlights the biological implications of CEBPB in CRC tumorigenesis,shedding new light on the etiology of CRC.

关键词： susceptibility genes gene screening models multi-omics GWAS CEBPB long-range promoter-enhancer interactions

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Gapless Genome Assembly of ZH8015 and Preliminary multi-omics Analysis to Investigate ZH8015's Responses Against Brown Planthopper Infestation

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Rice science 2024年第3期31卷 317-327,I0042-I0045页

作者： LI Dian DUAN Wenjing LIU Qun’en WU Weixun ZHAN Xiaodeng SUN Lianping ZHANG Yingxin CHENG Shihua State Key Laboratory of Rice Biology and Breeding China National Rice Research InstituteHangzhou 310006China

Accurate genomic information is essential for advancing genetic breeding research in specific rice varieties.This study presented a gapless genome assembly of the indica rice cultivar Zhonghui 8015(ZH8015)using Pac Bio HiFi,Hi-C,and ONT(Oxford Nanopore Technologies)ultra-long sequencing technologies,annotating 43037 gene structures.Subsequently,utilizing this genome along with transcriptomic and metabolomic techniques,we explored ZH8015's response to brown planthopper(BPH)infestation.Continuous transcriptomic sampling indicated significant changes in gene expression levels around 48 h after BPH feeding.Enrichment analysis revealed particularly significant alterations in genes related to reactive oxygen species scavenging and cell wall formation.Metabolomic results demonstrated marked increases in levels of several monosaccharides,which are components of the cell wall and dramatic changes in flavonoid contents.omics association analysis identified differentially expressed genes associated with key metabolites,shedding light on ZH8015's response to BPH infestation.In summary,this study constructed a reliable genome sequence resource for ZH8015,and the preliminary multi-omics results will guide future insect-resistant breeding research.

关键词： brown planthopper gapless genome genome assembly multi-omics Nilaparvata lugens rice

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Correlation between the gut microbiome and neurodegenerative diseases:a review of metagenomics evidence

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Neural Regeneration Research 2024年第4期19卷 833-845页

作者： Xiaoyan Liu Yi Liu Junlin Liu Hantao Zhang Chaofan Shan Yinglu Guo Xun Gong Mengmeng Cui Xiubin Li Min Tang School of Life Sciences Jiangsu University Institute of Animal Husbandry Jiangsu Academy of Agricultural Sciences Department of Rheumatology&Immunology Affiliated Hospital of Jiangsu University Department of Neurology The Second Affiliated Hospital of Shandong First Medical University

A growing body of evidence suggests that the gut microbiota contributes to the development of neurodegenerative diseases via the microbiota-gut-brain axis.As a contributing factor,microbiota dysbiosis always occurs in pathological changes of neurodegenerative diseases,such as Alzheimer’s disease,Parkinson’s disease,and amyotrophic lateral sclerosis.High-throughput sequencing technology has helped to reveal that the bidirectional communication between the central nervous system and the enteric nervous system is facilitated by the microbiota’s diverse microorganisms,and for both neuroimmune and neuroendocrine systems.Here,we summarize the bioinformatics analysis and wet-biology validation for the gut metagenomics in neurodegenerative diseases,with an emphasis on multi-omics studies and the gut virome.The pathogen-associated signaling biomarkers for identifying brain disorders and potential therapeutic targets are also elucidated.Finally,we discuss the role of diet,prebiotics,probiotics,postbiotics and exercise interventions in remodeling the microbiome and reducing the symptoms of neurodegenerative diseases.

关键词： biomarker diet pattern gut microbiota gut-brain axis metagenomics mitochondrial dysfunction multi-omics neurodegenerative disease neuroinflammation probiotic

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The multi-omics basis of potato heterosis

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Journal of Integrative Plant Biology 2022年第3期64卷 671-687页

作者： Dawei Li Xiaoyue Lu Yanhui Zhu Jun Pan Shaoqun Zhou Xinyan Zhang Guangtao Zhu Yi Shang Sanwen Huang Chunzhi Zhang Guangdong Laboratory of Lingnan Modern Agriculture Genome Analysis Laboratory of the Ministry of Agriculture and Rural AffairsAgricultural Synthetic Biology CenterAgricultural Genomics Institute at ShenzhenChinese Academy of Agricultural SciencesShenzhen 518172China Yunnan Key Laboratory of Potato Biology The AGISCAAS-YNNU Joint Academy of Potato SciencesYunnan Normal UniversityKunming 650500China

Heterosis is a fundamental biological phenomenon characterized by the superior performance of hybrids over their parents.Although tremendous progress has been reported in seed crops,the molecular mechanisms underlying heterosis in clonally propagated crops are largely unknown.Potato(Solanum tuberosum L.)is the most important tuber crop and an ongoing revolution is transforming potato from a clonally propagated tetraploid crop into a seed-propagated diploidhybrid potato.In our previous study,we developed the first generation of highly homozygous inbred lines of potato and hybrids with strong heterosis.Here,we integrated transcriptome,metabolome,and DNA methylation data to explore the genetic and molecular basis of potato heterosis at three developmental stages.We found that the initial establishment of heterosis in diploid potato was mainly due to dominant complementation.Flower color,male fertility,and starch and sucrose metabolism showed obvious gene dominant complementation in hybrids,and hybrids devoted more energy to primary metabolism for rapid growth.In addition,we identified~2700 allele-specific expression genes at each stage,which likely function in potato heterosis and might be regulated by CHH allele-specific methylation level.Our multi-omics analysis provides insight into heterosis in potato and facilitates the exploitation of heterosis in potato breeding.

关键词： allele-specific expression dominance DNA methylation heterosis metabolome multi-omics potato transcriptome

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multi-omics for COVID-19:driving development of therapeutics and vaccines

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National Science Review 2023年第9期10卷 307-336页

作者： Mengyu Guo Muya Xiong Jinying Peng Tong Guan Haixia Su Yanyi Huang Cai-Guang Yang Yang Li Diana Boraschi Thanigaimalai Pillaiyar Guanbo Wang Chengqi Yi Yechun Xu Chunying Chen CAS Key Laboratory of Biomedical Effects of Nanomaterials and Nanosafety and CAS Center for Excellence in Nanoscience National Center for Nanoscience and Technology of China State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Chinese Academy of Sciences University of Chinese Academy of Sciences State Key Laboratory of Protein and Plant Gene Research School of Life Sciences Peking University Biomedical Pioneering Innovation Centre Peking University 6. Institute for Cell AnalysisShenzhen Bay Laboratory Peking-Tsinghua Center for Life Sciences Peking University College of Chemistry and Molecular Engineering Beijing National Laboratory for Molecular SciencesPeking University 9. State Key Laboratory of Drug Research Centre for Chemical BiologyShanghai Institute of Materia MedicaChinese Academy of Sciences 10. Laboratory of Immunology and Nanomedicine and China-Italy Joint Laboratory of Pharmacobiotechnology for Medical ImmunomodulationShenzhen Institute of Advanced TechnologyChinese Academy of Sciences 11. Institute of Biochemistry and Cell Biology National Research Council 12. Institute of PharmacyPharmaceutical/Medicinal Chemistry and Tuebingen Center for Academic Drug Discovery Eberhard Karls University Tübingen 13. Department of Chemical Biology and Synthetic and Functional Biomolecules CenterCollege of Chemistry and Molecular Engineering Peking University 14. GBA National Institute for Nanotechnology Innovation

The ongoing COVID-19 pandemic caused by SARS-CoV-2 has raised global concern for public health and economy.The development of therapeutics and vaccines to combat this virus is continuously progressing.multi-omics approaches,including genomics,transcriptomics,proteomics,metabolomics,epigenomics and metallomics,have helped understand the structural and molecular features of the virus,thereby assisting in the design of potential therapeutics and accelerating vaccine development for COVID-19.Here,we provide an up-to-date overview of the latest applications of multi-omics technologies in strategies addressing COVID-19,in order to provide suggestions towards the development of highly effective knowledge-based therapeutics and vaccines.

关键词： COVID-19 SARS-CoV-2 multi-omics antibodies small-molecule drugs vaccines

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multi-omics-Guided Discovery of omicsynins Produced by Streptomyces sp.1647:Pseudo-Tetrapeptides Active Against Influenza A Viruses and Coronavirus HCoV-229E

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Engineering 2022年第9期16卷 176-186页

作者： Hongmin Sun Xingxing Li Minghua Chen Ming Zhong Yihua Li Kun Wang Yu Du Xin Zhen Rongmei Gao Yexiang Wu Yuanyuan Shi Liyan Yu Yongsheng Che Yuhuan Li Jian-Dong Jiang Bin Hong Shuyi Si NHC Key Laboratory of Biotechnology of Antibiotics Institute of Medicinal BiotechnologyChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China CAMS Key Laboratory of Synthetic Biology for Drug Innovation Institute of Medicinal BiotechnologyChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China CAMS Key Laboratory of Antiviral Drug Research Institute of Medicinal BiotechnologyChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China

Many microorganisms have mechanisms that protect cells against attack from viruses.The fermentation components of Streptomyces sp.1647 exhibit potent anti-influenza A virus(IAV)activity.This strain was isolated from soil in southern China in the 1970s,but the chemical nature of its antiviral substance(s)has remained unknown until now.We used an integrated multi-omics strategy to identify the antiviral agents from this streptomycete.The antibiotics and Secondary Metabolite Analysis Shell(antiSMASH)analysis of its genome sequence revealed 38 biosynthetic gene clusters(BGCs)for secondary metabolites,and the target BGCs possibly responsible for the production of antiviral components were narrowed down to three BGCs by bioactivity-guided comparative transcriptomics analysis.Through bioinformatics analysis and genetic manipulation of the regulators and a biosynthetic gene,cluster 36 was identified as the BGC responsible for the biosynthesis of the antiviral compounds.Bioactivity-based molecular networking analysis of mass spectrometric data from different recombinant strains illustrated that the antiviral compounds were a class of structural analogues.Finally,18 pseudo-tetrapeptides with an internal ureido linkage,omicsynins A1–A6,B1–B6,and C1–C6,were identified and/or isolated from fermentation broth.Among them,11 compounds(omicsynins A1,A2,A6,B1–B3,B5,B6,C1,C2,and C6)are new compounds.omicsynins B1–B4 exhibited potent antiviral activity against IAV with the 50%inhibitory concentration(IC_(50))of approximately 1μmol·L^(-1)and a selectivity index(SI)ranging from 100 to 300.omicsynins B1–B4 also showed significant antiviral activity against human coronavirus HCoV-229E.By integrating multi-omics data,we discovered a number of novel antiviral pseudo-tetrapeptides produced by Streptomyces sp.1647,indicating that the secondary metabolites of microorganisms are a valuable source of novel antivirals.

关键词： multi-omics Anti-influenza A virus Anti-coronavirus Streptomyces sp.1647 Pseudo-tetrapeptides

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Dissecting the brain with spatially resolved multi-omics

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药物分析学报:英文版 2023年第7期13卷 694-710页

作者： Yijia Fangma Mengting Liu Jie Liao Zhong Chen Yanrong Zheng Key Laboratory of Neuropharmacology and Translational Medicine of Zhejiang Province School of Pharmaceutical SciencesZhejiang Chinese Medical UniversityHangzhou310053China Pharmaceutical Informatics Institute College of Pharmaceutical SciencesZhejiang UniversityHangzhou310058China

Recent studies have highlighted spatially resolved multi-omics technologies,including spatial genomics,transcriptomics,proteomics,and metabolomics,as powerful tools to decipher the spatial heterogeneity of the brain.Here,we focus on two major approaches in spatial transcriptomics(next-generation sequencing-based technologies and image-based technologies),and mass spectrometry imaging technologies used in spatial proteomics and spatial metabolomics.Furthermore,we discuss their applications in neuroscience,including building the brain atlas,uncovering gene expression patterns of neurons for special behaviors,deciphering the molecular basis of neuronal communication,and providing a more comprehensive explanation of the molecular mechanisms underlying central nervous system disorders.However,further efforts are still needed toward the integrative application of multi-omics technologies,including the real-time spatial multi-omics analysis in living cells,the detailed gene profile in a whole-brain view,and the combination of functional verification.

关键词： Central nervous system disorders multi-omics Spatial transcriptomics Spatial proteomics Spatial metabolomics

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Comprehensive silk gland multi-omics comparison illuminates two alternative mechanisms in silkworm heterosis

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Zoological Research 2022年第4期43卷 585-596页

作者： Han Xu Lei Chen Xiao-Ling Tong Hai Hu Li-Yuan Liu Gui-Chun Liu Ya-Nan Zhu Ruo-Ping Zhao Wen Wang Fang-Yin Dai Xin Li Hui Xiang School of Medicine Shenzhen Campus of Sun Yat-Sen UniversityShenzhenGuangdong 518107China Guangdong Provincial Key Laboratory of Insect Developmental Biology and Applied Technology Guangzhou Key Laboratory of Insect Development Regulation and Application ResearchInstitute of Insect Science and TechnologySchool of Life SciencesSouth China Normal UniversityGuangzhouGuangdong 510631China School of Ecology and Environment Northwestern Polytechnical UniversityXi’anShaanxi 710072China State Key Laboratory of Silkworm Genome Biology Key Laboratory of Sericultural Biology and Genetic BreedingMinistry of Agriculture and Rural AffairsCollege of BiotechnologySouthwest UniversityChongqing 400715China State Key Laboratory of Genetic Resources and Evolution Kunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650223China

Heterosis is a common phenomenon in plants and animals with diverse underlying mechanisms.Here,we applied two widely used silkworm hybrid systems and performed multi-omics analysis to identify possible intrinsic associations between different hybrid strategies and epigenetic mechanisms with silkworm heterosis.We found significant differences in the silk gland transcriptomic landscape between the two systems,including differentially expressed genes and expression patterns in the hybrid offspring compared to their parents.In the quaternary hybrid system,hybrid vigor was primarily due to upregulated genes and the parent-dominant upregulated expression pattern,involving multiple transport processes,cellular nitrogen compound catabolism,glucose metabolism,and tricarboxylic acid cycle.In the binary system,hybrid vigor was mainly due to the down-regulated genes and transgressively down-regulated expression pattern,mainly involving basic nitrogen synthesis metabolism and body function.We also demonstrated that DNA methylation may affect hybrid vigor by regulating the expression of several heterosis-related genes.Thus,this study revealed two alternative mechanisms that may contribute to silkworm heterosis,both of which facilitate the efficient utilization of energy and nitrogen for silk production.

关键词： Heterosis Silkworm Hybrid systems multi-omics Silk production

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