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Advances and applications in single-cell and spatial genomics

Science China Life Sciences 2025年

作者： Jingjing Wang Fang Ye Haoxi Chai Yujia Jiang Teng Wang Xia Ran Qimin Xia Ziye Xu Yuting Fu Guodong Zhang Hanyu Wu Guoji Guo Hongshan Guo Yijun Ruan Yongcheng Wang Dong Xing Xun Xu Zemin Zhang beijing Advanced Innovation center for Genomics (ICG) Peking University Guangdong Provincial Key Laboratory of genome Read and Write BGI Research Bone Marrow Transplantation center of the First Affiliated Hospital & Liangzhu Laboratory Zhejiang University School of Medicine Life Sciences Institute and The Second Affiliated Hospital Zhejiang University BGI Research Biomedical Pioneering Innovation center (BIOPIC) and School of Life Sciences Peking University Academy for Advanced Interdisciplinary Studies Peking University Institute of Hematology Zhejiang University Department of Laboratory Medicine of The First Affiliated Hospital & Liangzhu Laboratory Zhejiang University School of Medicine center for Stem Cell and Regenerative Medicine Zhejiang University School of Medicine Zhejiang Provincial Key Lab for Tissue Engineering and Regenerative Medicine Dr.Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine

The applications of single-cell and spatial technologies in recent times have revolutionized the present understanding of cellular states and the cellular heterogeneity inherent in complex biological systems. These advancements offer unprecedented resolution in the examination of the functional genomics of individual cells and their spatial context within tissues. In this review, we have comprehensively discussed the historical development and recent progress in the field of single-cell and spatial genomics. We have reviewed the breakthroughs in single-cell multi-omics technologies, spatial genomics methods, and the computational strategies employed toward the analyses of singlecell atlas data. Furthermore, we have highlighted the advances made in constructing cellular atlases and their clinical applications,particularly in the context of disease. Finally, we have discussed the emerging trends, challenges, and opportunities in this rapidly evolving field.

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Common SNPs of APM1 Gene Are Not Associated With Hypertension or Obesity in chinese Population

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Biomedical and Environmental Sciences 2006年第3期19卷 179-184页

作者： WEI-LI YAN SHU-FENG CHEN JIAN-FENG HUANG YAN SHENA BO-QIN QIANG DONG-HAI LIU DONG-FENG GU Division of Population Genetics and Prevention Cardiovascular Institute and Fuwai Hospital Chinese Academy of Medical Sciences and Peking Union Medical College 167 Beilishi Road Beijing 100037 China national human genome center North Yongchang Rd 3-707 Beijing 100176 China

Objective To investigate whether the common variants 45T/G and 276G/T in APM1 gene were associated with hypertension combined with obesity （HO） and related clinical features in chinese Han population. Methods A case-control study design was applied. Common polymorphisms of 45T/G and 276G/T were genotyped by PCR product sequencing in 484 cases with HO and 502 controls with normal blood presure and BMI 〈 25. Results The genotype and allele frequencies of 45T/G, 276G/T, and haplotype defined by the two variants in cases did not differ from those in controls. The means of blood pressure, BMI and waist-hip ratio did not differ among genotypes of the two polymorphisms and haplotypes. Among lipid profiles, only serum high-density lipoprotein cholesterol （HDL-C） levels were significantly lower in T allele carders than that in non-T carriers after adjusting possible confounding factors （1.21 vs 1.32 mmol/L, P=0.0001）. Condusion Polymorphisms of 45T/G and 276G/T in APM1 gene are not associated with hypertension or obesity, or their clinical features in chinese Han population. Common polymorphism of 45T/G might be associated with serum HDL-C levels in chinese.

关键词： Adiponectin HDL-C Hypertension Obesity

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Several characteristics of contemporary climate change in the Tibetan Plateau

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Science China Earth Sciences 2001年第S1期44卷 410-420页

作者：朱文琴陈隆勋周自江 chinese Academy of Meteorological Sciences Beijing China national Meteorological center of China Beijing China

Characteristics of contemporary climate change in the Tibetan Plateau have been investigated based on the observational data of monthly mean air temperature, monthly mean maximum and minimum air temperatures, and precipitation amount at 217 stations in the Plateau and its adjacent areas in 1951-1998, in which the temperature data at Lhasa, Lanzhou, Kunming and Chengdu were extended to a period of 1935-1950. The following conclusions can be drawn. (1) The air temperature in the Tibetan Plateau decreased from the 1950s to the 1960s, afterwards it began warming up to the 1990s. The data at the Lhasa Station beginning from 1935 have indicated that the air temperature at the station was the highest in the 1940s, then it became cooling until the 1960s. After the 1960s, it began warming until the 1990s. However, the air temperature at Lhasa in the 1990s still did not reach as high as in the 1940s. (2) Since the 1960s, there has existed a cooling belt below 3000 m altitude above sea level, which is located in eastern and southeastern Tibetan Plateau, and there has existed a strong warming belt from south to north in 85-95°E. Because there are very nonhomogeneous and positive-negative alternating changes between cooling and warming belts, the air temperature is not linearly increased with increasing height. (3) Since the 1960s, there has existed a precipitation decreasing belt distributed over southwestern to northeastern Plateau as well as over a below 3000 m a.s.l. area in southeastern Plateau. The warming with decreasing precipitation occurs in the central area of the Plateau and the above 3000 m western Plateau; the warming with increasing precipitation occurs in the northern and southern Plateau; and the cooling with decreasing precipitation occurs in the below 3000 m southeastern Plateau.

关键词： climate change in China air temperature and precipitation maximum and minimum air temperatures annual mean air temperature anomalies.

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Incidence,predictors,and prognosis of thrombocytopenia among patients undergoing intra-aortic balloon pumping in the intensive care unit:a propensity score analysis

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Journal of Geriatric Cardiology 2021年第2期18卷 123-134,I0002页

作者： Wei TONG Jun-Mei WANG Jia-Yue LI Pei-Yao LI Yun-Dai CHEN Zheng-Bo ZHANG Wei DONG Department of Cardiology the Sixth Medical CentreChinese PLA General HospitalBeijingChina center for Artificial Intelligence in Medicine Chinese PLA General HospitalBeijingChina CAS Key Laboratory of genome Sciences and Information Beijing Institute of GenomicsChinese Academy of SciencesChina National Center for BioinformationBeijingChina Global Health Drug Discovery Institute BeijingChina

OBJECTIVE To explore the incidence,predictors,and prognosis of intra-aortic balloon pumping(IABP)-related thrombocytopenia in critically ill *** This multi-center study used the eICU Collaborative Research Database V1.2,comprising data on>130,000 patients from multiple intensive care units(ICUs)in America between 2014 and 2015.A total of 710 patients undergoing IABP were *** was defined as a drop in platelet count>50%from *** the cohort,167 patients who developed thrombocytopenia were matched 1:1 with 167 patients who did not,after propensity score(PS)*** associations between IABP-related thrombocytopenia and clinical outcomes were examined by multivariable logistic *** Among 710 patients undergoing IABP,249 patients(35.07%)developed *** APACHE IVa score was a predictor of thrombocytopenia[adjusted odds ratio(OR)=1.09,95%confidence interval(CI):1.02−1.15].After 1:1 PS matching,in-hospital mortality(adjusted OR=0.76,95%CI:0.37−1.56)and in-ICU mortality(adjusted OR=0.74,95%CI:0.34−1.63)were similar between the thrombocytopenia and non-thrombocytopenia ***,major bleeding occurred more frequently in the thrombocytopenia group(adjusted OR=2.54,95%CI:1.54−4.17).In-hospital length of stay(LOS)and in-ICU LOS were significantly longer in patients who developed thrombocytopenia than in those who did not(9.71 vs.7.36,P<0.001;5.13 vs.2.83,P<0.001).CONCLUSIONS Among patients undergoing IABP in the ICUs,thrombocytopenia was not associated with a difference in inhospital mortality or in-ICU mortality;however,thrombocytopenia was significantly associated with a greater risk of major bleeding and increased in-ICU and in-hospital LOS.

关键词： patients balloon thrombocytopenia

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Teleconnection between the Indian summer monsoon onset and the Meiyu over the Yangtze River Valley

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Science China Earth Sciences 2008年第7期51卷 1021-1035页

作者： LIU YunYun1,2,3 & DING YiHui2 1 chinese Academy of Meteorological Sciences, beijing 100081, China 2 national Climate center, beijing 100081, China 3 Graduate University of chinese Academy of Sciences, beijing 100049, China chinese Academy of Meteorological Sciences Beijing China national Climate center Beijing China Graduate University of chinese Academy of Sciences Beijing China

Based on the Indian and chinese precipitation data and the NCEP-NCAR reanalysis circulation data, the relationship between the Indian summer monsoon (ISM) onset and the Meiyu over the Yangtze River Valley has been discussed by the methods of correlation analysis and composite analysis. The results show that the date of ISM onset over Kerala in the southwestern coast of the Indian Peninsula is about two weeks earlier than the beginning of the Meiyu over the Yangtze River Valley. After the outbreak of ISM, the teleconnection mode sets up from the western coast of India via the Bay of Bengal (BOB) to the Yangtze River Valley and southern Japan. It is different both in time and space from the telecon- nection mode which is from the northwest of India via the Tibetan Plateau to northern China. The for- mer mode is defined as the "south" teleconnection of the Asian summer monsoon, forming in the pe- riod of ISM onset; while the latter mode is called the "north" teleconnection, mainly occurring in the Asian monsoon culminant period. During the process of the "south" teleconnection’s formation, the Asian monsoon circulation has experienced a series of important changes: ISM onset, the northward movement of the south Asia high (SAH), the onset vortex occurrence, the eastward extension of the stronger tropical westerly belt, and the northeastward jump of the western Pacific subtropical high (WPSH), etc. Consequently, since ISM sets up over Kerala, the whole Asian continent is covered by the upper SAH after about two weeks, while in the mid- and lower troposphere, a strong wind belt forms from the Arabian Sea via the southern India, BOB and the South China Sea (SCS), then along the western flank of WPSH, to the Yangtze River Valley and southern Japan. With the northward moving of the subtropical jet streams, the upper westerly jet stream and the low level jet have been coupled ver- tically over east Asia, while the Yangtze River Valley happens to locate in the ascending motion

关键词： Indian summer monsoon (ISM) the Meiyu over the Yangtze River Valley teleconnection mode

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Complete DNA sequence and gene analysis of the virulence plasmid pCP301 of Shigella flexneri 2a

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Science China Life Sciences 2003年第5期46卷 513-521+563页

作者：张继瑜刘红张笑兵杨剑杨帆杨国威沈岩侯云德金奇 Lanzhou Institute of Animal Science and Veterinary Pharmaceutics Chinese Academy of Agricultural Sciences Lanzhou 730050 China State Key Laboratory for Molecular Virology and Genetic Engineering State Key Laboratory for Molecular Virology and Genetic EngineeringState Key Laboratory for Molecular Virology and Genetic EngineeringChinese National Human Genome Center Beijing Beijing 100176 China State Key Laboratory for Molecular Virology and Genetic EngineeringState Key Laboratory for Molecular Virology and Genetic EngineeringChinese National Human Genome Center Beijing Beijing 100176 China State Key Laboratory for Molecular Virology and Genetic EngineeringState Key Laboratory for Molecular Virology and Genetic Engineering Beijing 100052 China Beijing 100052 China Beijing 100052 China Beijing 100052 China Beijing 100052 China Beijing 100052 China Beijing 100052 China

The complete nucleotide sequence and organization of the large virulence plasmid pCP301 (termed by us) of Shigella flexneri 2a strain 301 were determined and analyzed. The result showed that the entire DNA sequence of pCP301 is composed of 221618 bp which form a circular plasmid. Sequence analysis identified 272 open reading frames (ORFs), among which, 194 correspond to the proteins described previously, 61 have low identity (<60%) to known proteins and the rest 17 have no regions of significant homology with proteins in database. The genes of pCP301 mainly include the genes associated with bacterial virulence, the genes associated with regulation and the genes relating to plasmid maintenance, stability and DNA metabolism. Insertion sequence (IS) elements are 68 kb in length and account for 30 percent of complete sequence of the plasmid which indicates that gene multiple rearrangements of the pCP301 have taken place in Shigella flexneri evolution history. The research result is helpful for interpreting the pathogenesis of Shigella, as well as the genetics and evolution of the plasmid.

关键词： Shigella flexneri 2a virulence plasmid pCP301 DNA sequencing analysis.

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***:a probabilistic voting-based enhancer-promoter interaction prediction platform

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Journal of Genetics and Genomics 2023年第7期50卷 519-527页

作者： Yuyang Zhang Haoyu Wang Jing Liu Junlin Li Qing Zhang Bixia Tang Zhihua Zhang CAS Key Laboratory of genome Sciences and Information Beijing Institute of GenomicsChinese Academy of Sciencesand China National Center for BioinformationBeijing 100101China College of Life Sciences University of Chinese Academy of SciencesBeijing 100049China School of Artificial Intelligence University of Chinese Academy of SciencesBeijing 100049China

Enhancer promoter interaction(EPI)involves most of gene transcriptional regulation in the high *** the EPIs from given genomic loci or DNA sequences is not a trivial *** benchmarking work so far for EPI predictors is more or less empirical and lacks quantitative model-based comparisons,posing challenges for molecular biologists to obtain reliable EPI ***,we present an EPI prediction platform,namely *** on a statistic model of the data integration,*** is capable of comprehensively assessing the predictions from four state-of-the-art EPI *** with a userfriendly interface and visualization platform,*** presents the sorted results with the confidence of EPI relevance,which may guide the molecular biologists who lack the pre-knowledge of the algorithms of EPI ***,we showcase the utility of *** with a case *** provides a powerful tool to fuel the gene regulation and 3D genome studies by ease-to-access EPI *** can be freely accessed at https://***/deltaEPI/.

关键词： Enhancer-promoter interaction Hi-C Prediction Benchmark Web server

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A hypothetical model of trans-acting R-loops-mediated promoter-enhancer interactions by Alu elements

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Journal of Genetics and Genomics 2021年第11期48卷 1007-1019页

作者： Xue Bai Feifei Li Zhihua Zhang CAS Key Laboratory of genome Sciences and Information Beijing Institute of GenomicsChinese Academy of SciencesChina National Center for BioinformationBeijing 100101China School of Life Science University of Chinese Academy of SciencesBeijing 100101China School of Artificial Intelligence University of Chinese Academy of SciencesBeijing 100101China

Enhancers modulate gene expression by interacting with *** of enhancer-promoter interactions(EPIs)in the literature involve the activity of many components,including transcription factors and nucleic ***,the role that sequence similarity plays in EPIs remains largely ***,we report that Alu-derived sequences dominate sequence similarity between enhancers and *** rejecting alternative DNA:DNA and DNA:RNA triplex models,we propose that enhancer-associated RNAs(eRNAs)may directly contact their targeted promoters by forming trans-acting R-loops at those Alu *** show how the characteristic distribution of functional genomic data,such as RNA-DNA proximate ligation reads,binding of transcription factors,and RNA-binding proteins,all align with the Alu sequences of *** also show that these aligned Alu sequences may be subject to the constraint of coevolution,further implying the functional significance of these R-loop ***,our results imply that eRNA and Alu elements associate in a manner previously unrecognized in EPIs and the evolution of gene regulation networks in mammals.

关键词： Alu Enhancer-promoter interaction eRNA R-loop

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Optimization of terahertz monolithic integrated frequency multiplier based on trap-assisted physics model of THz Schottky barrier varactor

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chinese Physics B 2020年第10期29卷 308-314页

作者： Lu-Wei Qi Jin Meng Xiao-Yu Liu Yi Weng Zhi-Cheng Liu De-Hai Zhang Jing-Tao Zhou Zhi Jin Institute of Microelectronics of the chinese Academy of Sciences Beijing 100029China national Space Science center the Chinese Academy of SciencesBeijing 100190China University of chinese Academy of Sciences Beijing 100190China

The optimization of high power terahertz monolithic integrated circuit (TMIC) is systemically studied based on the physical model of the Schottky barrier varactor (SBV) with interface defects and tunneling effect. An ultra-thin dielectric layer is added to describe the extra tunneling effect and the damping of thermionic emission current induced by the interface defects. Power consumption of the dielectric layer results in the decrease of capacitance modulation ration (Cmax/Cmin), and thus leads to poor nonlinear C–V characteristics. The proposed Schottky metal-brim (SMB) terminal structure could improve the capacitance modulation ration by reducing the influence of the interface charge and eliminating the fringing capacitance effect. Finally, a 215 GHz tripler TMIC is fabricated based on the SMB terminal structure. The output power is above 5 mW at 210–218 GHz and the maximum could exceed 10 mW at 216 GHz, which could be widely used in terahertz imaging, radiometers, and so on. This paper also provides theoretical support for the SMB structure to optimize the TMIC performance.

关键词： C-V characteristic physics-based model terahertz monolithic integrated circuit(TMIC) Schottky barrier varactor

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Superconductivity in Mg-Doped Layered Intermetallic Compound NbB2

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chinese Physics Letters 2008年第2期25卷 687-690页

作者：刘广同金灏李政耿红霞车广灿金铎孙连峰解思深雒建林 beijing national Laboratory for Condensed Matter Physics Institute of Physics Chinese Academy of Sciences Beijing 100080 national center for Nanoscience and Technology Beijing 100080

We have performed low temperature resistivity p（T） and specific heat C（T） measurements on a superconducting polycrystalline Nb0.75Mg0.25B2 sample. The results indicate that the superconducting transition temperature is -4.6 K. The zero temperature upper critical field determined from the resistivity and specific heat is 3123 Oe. The electronic coefficient of specific heat γn=4.51 mJmol^-1K^2 and the Debye temperature θD=419 K are obtained by fitting the zero-field specific heat data in the normal state. At low temperatures, the electronic specific heat in the superconducting state follows Ces/γnTc = 2.84 exp（-1.21Tc/T）. This indicates that the superconducting pairing in Nb0.75Mg0.25B2 has s-wave symmetry.

关键词： TRANSITION-TEMPERATURE HEAT DEPENDENCE DIBORIDES TRANSPORT STATES

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