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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

The sexually dimorphic expression of glutamate transporters and their implication in pain after spinal cord injury

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Neural Regeneration Research 2025年第11期20卷 3317-3329页

作者： Jennifer M.Colón-Mercado Aranza I.Torrado-Tapias Iris K.Salgado Jose M.Santiago Samuel E.Ocasio Rivera Dina P.Bracho-Rincon Luis H.Pagan Rivera Jorge D.Miranda Department of Physiology University of Puerto RicoMedical Sciences CampusSan JuanPRUSA National Institutes of Health National Human Genome Research InstituteBethesdaMDUSA Universidad Central del Caribe School of MedicineBayamónPRUSA University of Puerto Rico Carolina CampusCarolinaPRUSA Institute of Neurobiology San JuanPRUSA

In addition to the loss of motor function,~60% of patients develop pain after spinal cord *** cellular-molecular mechanisms are not well understood,but the data suggests that plasticity within the rostral,epicenter,and caudal penumbra of the injury site initiates a cellularmolecular interplay that acts as a rewiring mechanism leading to central neuropathic *** can lead to the formation of new connections triggering abnormal sensory *** excitatory glutamate transporters are responsible for the reuptake of extracellular glutamate which makes them a critical target to prevent neuronal hyperexcitability and *** previous studies showed a sexually dimorphic therapeutic window for spinal cord injury after treatment with the selective estrogen receptor modulator *** this study,we investigated the anti-allodynic effects of tamoxifen in male and female rats with spinal cord *** hypothesized that tamoxifen exerts anti-allodynic effects by increasing the expression of glutamate transporters,leading to reduced hyperexcitability of the secondary neuron or by decreasing aberrant *** and female rats received a moderate contusion to the thoracic spinal cord followed by subcutaneous slow-release treatment of tamoxifen or matrix pellets as a control(placebo).We used von Frey monofilaments and the“up-down method”to evaluate mechanical *** treatment decreased allodynia only in female rats with spinal cord injury revealing a sexdependent *** expression profile of glutamatergic transporters(excitatory amino acid transporter 1/glutamate aspartate transporter and excitatory amino acid transporter 2/glutamate transporter-1)revealed a sexual dimorphism in the rostral,epicenter,and caudal areas of the spinal cord with a pattern of expression primarily on *** rodents showed a significantly higher level of excitatory amino acid transporter-1 expression while male rodents showed increased

关键词： allodynia central neuropathic pain EAAT-1/GLAST EAAT-2/GLT-1 glutamate transporters selective estrogen receptor modulator sexual dimorphism spinal cord injury trauma

Transcriptional regulation in the development and dysfunction of neocortical projection neurons

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Neural Regeneration Research 2024年第2期19卷 246-254页

作者： Ningxin Wang Rong Wan Ke Tang Precise genome Engineering center School of Life SciencesGuangzhou UniversityGuangzhouGuangdong ProvinceChina

Glutamatergic projection neurons generate sophisticated excitatory circuits to integrate and transmit information among different cortical areas,and between the neocortex and other regions of the brain and spinal *** development of cortical projection neurons is regulated by certain essential events such as neural fate determination,proliferation,specification,differentiation,migration,survival,axonogenesis,and *** processes are precisely regulated in a tempo-spatial manner by intrinsic factors,extrinsic signals,and neural *** generation of correct subtypes and precise connections of projection neurons is imperative not only to support the basic cortical functions(such as sensory information integration,motor coordination,and cognition)but also to prevent the onset and progression of neurodevelopmental disorders(such as intellectual disability,autism spectrum disorders,anxiety,and depression).This review mainly focuses on the recent progress of transcriptional regulations on the development and diversity of neocortical projection neurons and the clinical relevance of the failure of transcriptional modulations.

关键词： autism spectrum disorders cognition differentiation excitatory circuits intellectual disability neocortex neurodevelopmental disorders projection neuron specification transcriptional regulation

Computational screening of doping schemes for LiTi2(PO4)3 as cathode coating materials

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Chinese Physics B 2020年第3期29卷 7-12页

作者： Yu-Qi Wang Xiao-Rui Sun Rui-Juan Xiao Li-Quan Chen Beijing Advanced Innovation center for Materials genome Engineering Institute of PhysicsChinese Academy of SciencesBeijing 100190China University of Chinese Academy of sciences Beijing 100190China

In all-solid-state lithium batteries,the impedance at the cathode/electrolyte interface shows close relationship with the cycle *** coatings are helpful to reduce the impedance and increase the stability at the interface ***2(PO4)3(LTP),a fast ion conductor with high ionic conductivity approaching 10^(-3)S·cm^(-1),is adopted as the coating materials in this *** crystal and electronic structures,as well as the Li^+ion migration properties are evaluated for LTP and its doped derivatives based on density functional theory(DFT)and bond valence(BV)*** part of Ti sites with element Mn,Fe,or Mg in LTP can improve the electronic conductivity of LTP while does not decrease its high ionic *** this way,the coating materials with both high ionic conductivities and electronic conductivities can be prepared for all-solid-state lithium batteries to improve the ion and electron transport properties at the interface.

关键词： lithium battery materials high-throughput calculations density functional theory virtual screening

AtGGM2014, an Arabidopsis gene co-expression network for functional studies

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Science China(Life sciences) 2015年第3期58卷 276-286页

作者： MA ShiSong BOHNERT Hans J DINESH-KUMAR Savithramma P Department of Plant Biology and the genome center College of Biological Sciences University of California Departments of Plant Biology and of Crop sciences University of Illinois at Urbana-Champaign

Gene co-expression networks provide an important tool for systems biology studies. Using microarray data from the Array Express database, we constructed an Arabidopsis gene co-expression network, termed At GGM2014, based on the graphical Gaussian model, which contains 102,644 co-expression gene pairs among 18,068 genes. The network was grouped into 622 gene co-expression modules. These modules function in diverse house-keeping, cell cycle, development, hormone response, metabolism, and stress response pathways. We developed a tool to facilitate easy visualization of the expression patterns of these modules either in a tissue context or their regulation under different treatment conditions. The results indicate that at least six modules with tissue-specific expression pattern failed to record modular regulation under various stress conditions. This discrepancy could be best explained by the fact that experiments to study plant stress responses focused mainly on leaves and less on roots, and thus failed to recover specific regulation pattern in other tissues. Overall, the modular structures revealed by our network provide extensive information to generate testable hypotheses about diverse plant signaling pathways. At GGM2014 offers a constructive tool for plant systems biology studies.

关键词： Arabidopsis gene co-expression network graphical Gaussian model plant development stress response hormone response

iBIG:An Integrative Network Tool for Supporting Human Disease Mechanism Studies

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Genomics, Proteomics & Bioinformatics 2013年第3期11卷 166-171页

作者： Jiya Sun Yuyun Pan Xuemei Feng Huijuan Zhang Yong Duan Hongxing Lei CAS Key Laboratory of genome sciences and Information Beijing Institute of GenomicsChinese Academy of Sciences Graduate University of Chinese Academy of sciences UC Davis genome center and Department of Biomedical Engineering

Understanding the mechanism of complex human diseases is a major scientitic challenge. Towards this end, we developed a web-based network tool named iBIG （stands for integrative BioloGy）, which incorporates a variety of information on gene interaction and regulation. The generated network can be annotated with various types of information and visualized directly online. In addition to the gene networks based on physical and pathway interactions, networks at a functional level can also be constructed. Furthermore, a supplementary R package is provided to process microarray data and generate a list of important genes to be used as input for iBIG. To demonstrate its usefulness, we collected 54 microarrays on common human diseases including cancer, neurolog- ical disorders, infectious diseases and other common diseases. We processed the microarray data with our R package and constructed a network of functional modules perturbed in common human diseases. Networks at the functional level in combination with gene networks may provide new insight into the mechanism of human diseases, iBIG is freely available at http：//***/ibig.

关键词： Network Functional module Disease mechanism Microarray Web server

A New Definition of Modularity for Community Detection in Complex Networks

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Chinese Physics Letters 2012年第9期29卷 230-234页

作者： YE Zhen-Qing ZHANG Ke HU Song-Nian YU Jun James D.Watson Institute of genome sciences College of Life SciencesZhejiang UniversityHangzhou 310058 CAS Key Laboratory of genome sciences and Information Beijing Institute GenomicsChinese Academy of SciencesBeijing 100029 Medical Systems Biology Research center Tsinghua University School of MedicineBeijing 100084

We propose a new definition of modularity,*** Qd function,for network analysis,which takes the edge density and topological structure of modules into account and is different from the original strategy of simply calculating the number of edges(the definition of modularity Q introduced by Newman and Girvan).Armed with this novel quality function Qd,we implement an adaptive clustering algorithm for process optimization,and apply our strategy to several synthetic and real-world *** results of our exercises demonstrate a better performance in extracting accurate community ingredients from complex networks.

关键词： network function Complex

GenBase: A Nucleotide Sequence Database

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Genomics, Proteomics & Bioinformatics 2024年第3期22卷 107-112页

作者： Congfan Bu Xinchang Zheng Xuetong Zhao Tianyi Xu Xue Bai Yaokai Jia Meili Chen Lili Hao Jingfa Xiao Zhang Zhang Wenming Zhao Bixia Tang Yiming Bao National Genomics Data center Beijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijing 100101China CAS Key Laboratory of genome sciences and Information Beijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijing 100101China Human genome Sequencing center Baylor College of MedicineHoustonTX 77030USA University of Chinese Academy of sciences Beijing 100049China

The rapid advancement of sequencing technologies poses challenges in managing the large volume and exponential growth of sequence data efficiently and on *** address this issue,we present GenBase(https://***/genbase),an open-access data repository that follows the International Nucleotide Sequence Database Collaboration(INSDC)data standards and structures,for efficient nucleotide sequence archiving,searching,and *** a core resource within the National Genomics Data center(NGDC)of the China National center for Bioinformation(CNCB;https://***),GenBase offers bilingual submission pipeline and services,as well as local submission assistance in *** also provides a unique Excel format for metadata description and feature annotation of nucleotide sequences,along with a real-time data validation system to streamline sequence *** of April 23,2024,GenBase received 68,251 nucleotide sequences and 689,574 annotated protein sequences across 414 species from 2319 *** of these,63,614(93%)nucleotide sequences and 620,640(90%)annotated protein sequences have been released and are publicly accessible through GenBase’s web search system,File Transfer Protocol(FTP),and Application Programming Interface(API).Additionally,in collaboration with INSDC,GenBase has constructed an effective data exchange mechanism with GenBank and started sharing released nucleotide ***,GenBase integrates all sequences from GenBank with daily updates,demonstrating its commitment to actively contributing to global sequence data management and sharing.

关键词： Nucleotide sequence Database GenBase GenBank INSDC

“Beijing Region” (3pter-D3S3397) of the Human genome: Complete sequence and analysis

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Science China(Life sciences) 2005年第4期48卷 311-329页

作者： The Chinese Human genome Sequencing Consortium Beijing Genomics Institute Chinese Academy of Sciences Beijing 101300 China /James D. Watson Institute of Genome Sciences Zhejiang University Hangzhou 310008 China Chinese National Human genome center at Shanghai (CHGC) Shanghai 201203 China Chinese National Human genome center Beijing (CHGB) Beijing 100176 China

The goal of the Human genome Project (HGP) is to determine a complete and high-quality sequence of the human genome. China, as one of the six member states, takes a region between 3pter and D3S3397 of the human chromosome 3 as its share of this historic project, referred as “Beijing Region”. The complete sequence of this region comprises of 17.4 megabasepairs (Mb) with an average GC content of 42% and an average recombination rate of 2.14 cM/Mb. Within Beijing Region, 122 known and 20 novel genes are identified, as well as 42607 single nucleotide polymorphisms (SNPs). Comprehensive analyses also reveal: (i) gene density and GC-content of Beijing Region are in agreement with human cytogenetic maps, i.e. G-minus bands are GC-rich and of a high gene density, whereas G-plus bands are GC-poor and of a relatively low gene density; (ii) the average recombination rate within Beijing Region is rela-tively high compared with other regions of chromosome 3, with the highest recombination rate of 6.06 cM/Mb in the subtelomeric area; (iii) it is most likely that a large gene, associated with the mammary gland, may reside in the 1.1 Mb gene-poor area near the telomere; (iv) many dis-ease-related genes are genetically mapped to Beijing Region, including those associated with cancers and metabolic syndromes. All make Beijing Region an important target for in-depth mo-lecular investigations with a purpose of medical applications.

关键词： Human genome Project (HGP), "Beijing Region", complete sequence, genome landscape, sequence annotation.