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Single-cell omics: experimental workflow, data analyses and applications

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Science China Life Sciences 2025年第1期68卷 5-102页

作者： Fengying Sun Haoyan Li Dongqing Sun Shaliu Fu Lei Gu Xin Shao Qinqin Wang Xin Dong Bin Duan Feiyang Xing Jun Wu Minmin Xiao Fangqing Zhao Jing-Dong J.Han Qi Liu Xiaohui Fan Chen Li Chenfei Wang Tieliu Shi Department of Clinical Laboratory the Affiliated Wuhu Hospital of East China Normal University (The Second People's Hospital of Wuhu City) Pharmaceutical Informatics Institute College of Pharmaceutical SciencesZhejiang University Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration (Tongji University) Ministry of EducationOrthopaedic DepartmentTongji HospitalBioinformatics DepartmentSchool of Life Sciences and TechnologyTongji University Frontier Science center for Stem Cells School of Life Sciences and TechnologyTongji University Translational Medical center for Stem Cell Therapy and Institute for Regenerative Medicine Shanghai East HospitalBioinformatics DepartmentSchool of Life Sciences and TechnologyTongji University Research Institute of Intelligent Computing Zhejiang Lab Shanghai Research Institute for Intelligent Autonomous Systems center for Single-cell Omics School of Public HealthShanghai Jiao Tong University School of Medicine National Key Laboratory of Chinese Medicine Modernization Innovation Center of Yangtze River DeltaZhejiang University center for Bioinformatics and Computational Biology Shanghai Key Laboratory of Regulatory Biologythe Institute of Biomedical Sciences and School of Life SciencesEast China Normal University Beijing Institutes of Life Science Chinese Academy of Sciences Peking-Tsinghua center for Life Sciences Academy for Advanced Interdisciplinary StudiesCenter for Quantitative Biology (CQB)Peking University Zhejiang Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases Women's HospitalZhejiang University School of Medicine Key Laboratory of Advanced Theory and Application in Statistics and data Science-MOE School of StatisticsEast China Normal University

Cells are the fundamental units of biological systems and exhibit unique development trajectories and molecular features. Our exploration of how the genomes orchestrate the formation and maintenance of each cell, and control the cellular phenotypes of various organismsis, is both captivating and intricate. Since the inception of the first single-cell RNA technology, technologies related to single-cell sequencing have experienced rapid advancements in recent years. These technologies have expanded horizontally to include single-cell genome, epigenome,proteome, and metabolome, while vertically, they have progressed to integrate multiple omics data and incorporate additional information such as spatial sc RNA-seq and CRISPR screening. Single-cell omics represent a groundbreaking advancement in the biomedical field,offering profound insights into the understanding of complex diseases, including cancers. Here, we comprehensively summarize recent advances in single-cell omics technologies, with a specific focus on the methodology section. This overview aims to guide researchers in selecting appropriate methods for single-cell sequencing and related data analysis.

关键词： single-cell sequencing genome epigenome proteomics metabolomics multimodal spatial transcriptomics CRISPR screening

Network-Based Predictions and Simulations by Biological State Space Models: Search for Drug Mode of Action

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Journal of Computer Science & Technology 2010年第1期25卷 131-153页

作者： Rui Yamaguchi Seiya Imoto Satoru Miyano Human genome center Institute of Medical Science University of Tokyo

Since time-course microarrav data are short but contain a large number of genes, most of statistical models should be extended so that they can handle such statistically irregular situations. We introduce biological state space models that are established as suitable computational models for constructing gene networks from microarray gene expression data. This chapter elucidates theory and methodology of our biological state space models together with some representative analyses including discovery of drug mode of action. Through the applications we show the whole strategy of biological state space model analysis involving experimental design of time-course data, model building and analysis of the estimated networks.

关键词： gene networks state space models time-course gene expression data

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

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Genomics, Proteomics & Bioinformatics 2020年第6期18卷 648-663页

作者： Xufei Teng Qianpeng Li Zhao Li Yuansheng Zhang Guangyi Niu Jingfa Xiao Jun Yu Zhang Zhang Shuhui Song China National center for Bioinformation Beijing 100101China National Genomics data center&CAS Key Laboratory of genome Sciences and Information Beijing Institute of GenomicsChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China

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 ***,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 *** 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 *** are tailored to two key mechanisms:strand-biased and function-associated *** 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 *** 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 *** actions are in desperate need,especially in the middle of the War against COVID-19.

关键词： SARS-CoV-2 Nucleotide composition Mutation spectrum Viral replication

Identification of Key Genes as Potential Drug Targets for Gastric Cancer

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Tsinghua Science and Technology 2023年第4期28卷 649-664页

作者： Md.Tofazzal Hossain Md.Selim Reza Yin Peng Shengzhong Feng Yanjie Wei center for High Performance Computing Joint Engineering Research Center for Health Big Data Intelligent Analysis TechnologyShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China School of Computer Science and Technology University of Chinese Academy of SciencesBeijing 100049China Department of Statistics Bangabandhu Sheikh Mujibur Rahman Science and Technology UniversityGopalganj 8100Bangladesh Guangdong Provincial Key Laboratory for genome Stability and Disease Prevention and Regional Immunity and Diseases Department of PathologyShenzhen UniversityShenzhen 518060China

Gastric cancer(GC)is one of the most common cancers and ranks the third in cancer mortality all over the *** goal of this study was to identify potential hub-genes,highlighting their functions,signaling pathways,and candidate drugs for the treatment of GC *** used publicly available next generation sequencing(NGS)data to identify differentially expressed(DE)*** top DE genes were mapped to STRING database to construct the protein-protein interaction(PPI)network and top hub genes were selected for further *** found a total of 1555 DE genes with 870 upregulated and 685 downregulated genes in *** selected the top 400(200 upregulated and 200 downregulated)genes to construct a PPI network and extracted the top 15 hub *** gene ontology(GO)term and kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analyses of the 15 hub genes exposed some important functions and signaling pathways that were significantly associated with GC *** survival analysis of the hub genes disclosed that the lower expressions of the three hub genes CDH2,COL4A1,and COL5A2 were associated with better survival of GC *** three genes might be the candidate biomarkers for the diagnosis and treatment of ***,we considered 3 key proteins(genomic biomarkers)(COL4A1,CDH2,and CO5A2)as the drug target proteins(receptors),performed their docking analysis with the 102 meta-drug agents,and found Everolimus,Docetaxel,Lanreotide,Venetoclax,Temsirolimus,and Nilotinib as the top ranked 6 candidate drugs with respect to our proposed target proteins for the treatment against GC ***,the proposed drugs might play vital role for the treatment against GC patients.

关键词： gastric cancer hub genes candidate genes molecular docking candidate drugs

Plant genomic resources at National Genomics data center:assisting in data-driven breeding applications

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aBIOTECH 2024年第1期5卷 94-106页

作者： Dongmei Tian Tianyi Xu Hailong Kang Hong Luo Yanqing Wang Meili Chen Rujiao Li Lina Ma Zhonghuang Wang Lili Hao Bixia Tang Dong Zou Jingfa Xiao Wenming Zhao Yiming Bao Zhang Zhang Shuhui Song National Genomics data center Beijing Institute of GenomicsChinese Academy of Sciences&China National Center for BioinformationBeijing 100101China CAS Key Laboratory of genome Sciences and Information Beijing Institute of GenomicsChinese Academy of Sciences&China National Center for BioinformationBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China

Genomic data serve as an invaluable resource for unraveling the intricacies of the higher plant systems,including the constituent elements within and among *** various efforts in genomic data archiving,integrative analysis and value-added curation,the National Genomics data center(NGDC),which is a part of the China National center for Bioinformation(CNCB),has successfully established and currently maintains a vast amount of database *** dedicated initiative of the NGDC facilitates a data-rich ecosystem that greatly strengthens and supports genomic research ***,we present a comprehensive overview of central repositories dedicated to archiving,presenting,and sharing plant omics data,introduce knowledgebases focused on variants or gene-based functional insights,highlight species-specific multiple omics database resources,and briefly review the online application *** intend that this review can be used as a guide map for plant researchers wishing to select effective data resources from the NGDC for their specific areas of study.

关键词： Plant-omics data data repositories data integration Knowledgebase Plant genomics

analysis of Transcriptome Changes Induced by Ptr ToxA in Wheat Provides Insights into the Mechanisms of Plant Susceptibility

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Molecular Plant 2009年第5期2卷 1067-1083页

作者： Iovanna Pandelova Melania F. Betts Viola A. Manning Larry J. Wilhelm Todd C. Mockler Lynda M. Ciuffetti Department of Botany and Plant Pathology and center for genome Research and Biocomputing Oregon State University Corvallis OR 97331 USA

To obtain greater insight into the molecular events underlying plant disease susceptibility, we studied transcriptome changes induced by a host-selective toxin of Pyrenophora tritici-repentis, Ptr ToxA （ToxA）, on its host plant, wheat. Transcriptional profiling of ToxA-treated leaves of a ToxA-sensitive wheat cultivar was performed using the GeneChip Wheat genome Array. An improved and up-to-date annotation of the wheat microarray was generated and a new tool for array data analysis （BRAT） was developed, and both are available for public use via a web-based interface. Our data indicate that massive transcriptional reprogramming occurs due to ToxA treatment, including cellular responses typically associated with defense. In addition, this study supports previous results indicating that ToxA-induced cell death is triggered by impairment of the photosynthetic machinery and accumulation of reactive oxygen species. Based on results of this study, we propose that ToxA acts as both an elicitor and a virulence factor.

关键词： Gene expression transcriptome analysis defense responses fungal pathogenesis plant-microbe interactions host-selective toxin.

Developing an atmospheric aging evaluation model of acrylic coatings:A semi-supervised machine learning algorithm

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International Journal of Minerals,Metallurgy and Materials 2024年第7期31卷 1617-1627页

作者： Yiran Li Zhongheng Fu Xiangyang Yu Zhihui Jin Haiyan Gong Lingwei Ma Xiaogang Li Dawei Zhang Beijing Advanced Innovation center for Materials genome Engineering Institute for Advanced Materials and TechnologyUniversity of Science and Technology BeijingBeijing 100083China National Materials Corrosion and Protection data center University of Science and Technology BeijingBeijing 100083China BRI Southeast Asia Network for Corrosion and Protection(MOE) Shunde Innovation School of University of Science and Technology BeijingFoshan 528399China

To study the atmospheric aging of acrylic coatings,a two-year aging exposure experiment was conducted in 13 representative climatic environments in *** atmospheric aging evaluation model of acrylic coatings was developed based on aging data including11 environmental factors from 567 cities.A hybrid method of random forest and Spearman correlation analysis was used to reduce the redundancy and multicollinearity of the data set by dimensionality reduction.A semi-supervised collaborative trained regression model was developed with the environmental factors as input and the low-frequency impedance modulus values of the electrochemical impedance spectra of acrylic coatings in 3.5wt%NaCl solution as *** model improves accuracy compared to supervised learning algorithms model(support vector machines model).The model provides a new method for the rapid evaluation of the aging performance of acrylic coatings,and may also serve as a reference to evaluate the aging performance of other organic coatings.

关键词： acrylic coatings coatings aging atmospheric environment machine learning

Comparative and integrative analysis of RNA structural profiling data： current practices and emerging questions

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Frontiers of Electrical and Electronic Engineering in China 2017年第1期5卷 3-24页

作者： Krishna Choudhary Fei Deng Sharon Aviran Department of Biomedical Engineering and genome center University of California at Davis Davis CA 95616 USA

Background： Structure profiling experiments provide single-nucleotide information on RNA structure. Recent advances in chemistry combined with application of high-throughput sequencing have enabled structure profiling at transeriptome scale and in living cells, creating unprecedented opportunities for RNA biology. Propelled by these experimental advances, massive data with ever-increasing diversity and complexity have been generated, which give rise to new challenges in interpreting and analyzing these data. Results： We review current practices in analysis of structure profiling data with emphasis on comparative and integrative analysis as well as highlight emerging questions. Comparative analysis has revealed structural patterns across transcriptomes and has become an integral component of recent profiling studies. Additionally, profiling data can be integrated into traditional structure prediction algorithms to improve prediction accuracy. Conclusions： To keep pace with experimental developments, methods to facilitate, enhance and refine such analyses are needed. Parallel advances in analysis methodology will complement profiling technologies and help them reach their full potential.

关键词： RNA structure profiling high-throughput sequencing RNA secondary structure prediction chemical structure probing SHAPE-Seq

genome-wide CRISPR screening reveals key genes and pathways associated with 20-hydroxyecdysone signal transduction in the silkworm(Bombyx mori)

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Insect Science 2024年第1期31卷 47-58页

作者： Hao Sun Jingya Chen Ruolin Wang Dan Liu Na Zhang Tong Zhang Ling Jia Sanyuan Ma Qingyou Xia State Key Laboratory of Silkworm genome Biology Southwest UniversityChongqingChina Biological Science Research center Southwest UniversityChongqingChina

Metamorphosis is a complex developmental process involving multiple pathways and a large number of genes that are regulated by juvenile hormone(JH)and 20-hydroxyecdysone(20E).Despite important progress in understanding various aspects of silkworm biology,the hormone signaling pathway in the silkworm remains poorly ***-wide screening using clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated protein 9(Cas9)-based libraries has recently emerged as a novel method for analyzing genome function,enabling further research into essential genes,drug targets,and virus-host ***,we constructed a genome-wide CRISPR/Cas9-based library of the silkworm(Bombyx mori)and successfully revealed the genes involved in biotic or abiotic stress factor *** this study,we used our silkworm CRISPR library and large-scale genome-wide screening to analyze the key genes in the silkworm 20E signaling pathway and their mechanisms of *** annotation showed that 20E regulates key proteins in processes that mainly occur in the cytoplasm and *** enrichment analysis showed that 20E can activate phosphorylation and may affect innate immunity,interfere with intracellular nutrition and energy metabolism,and eventually cause cell *** screening results were experimentally validated by generating cells with knockout alleles of the relevant genes,which had increased tolerance to *** findings provide a panoramic overview of signaling in response to 20E in the silkworm,underscoring the utility of genome-wide CRISPR mutant libraries in deciphering hormone signaling pathways and the mechanisms that regulate metamorphosis in insects.

关键词： CRISPR/Cas9 CRISPR library screening ecdysone 20E signal transduction silkworm whole genome editing