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ImSpiRE: image feature-aided spatial resolution enhancement method

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Science China life sciences 2025年第1期 272-283页

作者： Yuwei Hua Yizhi Zhang Zhenming Guo Shan Bian Yong Zhang State Key Laboratory of Cardiovascular Diseases and Medical innovation center Institute for Regenerative MedicineDepartment of NeurosurgeryShanghai East HospitalShanghai Key Laboratory of Signaling and Disease ResearchFrontier Science Center for Stem Cell ResearchSchool of Life Sciences and TechnologyTongji University

The resolution of most spatially resolved transcriptomic technologies usually cannot attain the single-cell level, limiting their applications in biological discoveries. Here, we introduce ImSpiRE, an image feature-aided spatial resolution enhancement method for in situ capturing spatial transcriptome. Taking the information stored in histological images, ImSpiRE solves an optimal transport problem to redistribute the expression profiles of spots to construct new transcriptional profiles with enhanced resolution, together with extending the gene expression profiles into unmeasured regions. Applications to multiple datasets confirm that ImSpiRE can enhance spatial resolution to the subspot level while contributing to the discovery of tissue domains, signaling communication patterns, and spatiotemporal characterization.

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DNA End Resection:Facts and Mechanisms

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Genomics, Proteomics & Bioinformatics 2016年第3期14卷 126-130页

作者： Ting Liu Jun Huang Department of cell Biology and Program in Molecular cell Biology Zhejiang University School of Medicine life sciences institute and innovation center for cell signaling network Zhejiang University

DNA double-strand breaks（DSBs）,which arise following exposure to a number of endogenous and exogenous agents,can be repaired by either the homologous recombination（HR）or non-homologous end-joining（NHEJ） pathways in eukaryotic cells.A vital step in HR repair is DNA end resection,which generates a long 30single-stranded DNA（ss DNA） tail that can invade the homologous DNA *** generation of 30 ss DNA is not only essential for HR repair,but also promotes activation of the ataxia telangiectasia and Rad3-related protein（ATR）.Multiple factors,including the MRN/X complex,C-terminal-binding protein interacting protein（Ct IP）/Sae2,exonuclease 1（EXO1）,Bloom syndrome protein（BLM）/Sgs1,DNA2 nuclease/helicase,and several chromatin remodelers,cooperate to complete the process of end *** we review the basic machinery involved in DNA end resection in eukaryotic cells.

关键词： DNA end resection Homologous recombination DNA double-strand breaks Chromatin remodeling factors Genome stability

Neuronal insulin receptor mediates a positive feedback regulation of insulin biosynthesis in Drosophila

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Journal of Genetics and Genomics 2017年第2期44卷 123-125页

作者： Jie Ye Danping Chen Yue Yu Liming Wang life sciences institute Zhejiang UniversityHangzhou 310058China innovation center for cell signaling network Zhejiang UniversityHangzhou 310058China

Insulin signaling is vital for the development and growth of mammals,which also plays a prominent role in the regulation of metabolism,stress response,reproduction,and ***,insulin signaling is under tight regulation at the levels of insulin biosynthesis,secretion,and post-secretion action（Melloul et al.,2002;Na€ssel et al.,2013）.

关键词： biosynthesis Drosophila secretion Insulin metabolism vital tight neuronal physiological signaling

Fragmentation for selection: how the deleterious mt DNA is removed in the female germline

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Science Bulletin 2019年第22期64卷 1646-1648页

作者： Chao Tong MOE Key Laboratory for Biosystems Homeostasis & Protection and innovation center for cell signaling network Life Sciences Institute Zhejiang University The Second Affiliated Hospital School of Medicine Zhejiang University

Mitochondria are the energy factories and metabolic centers of cells,and their malfunction can lead to multiple human *** highly dynamic organelles,mitochondria undergo frequent fission and fusion processes[1].The fusion process enables the exchange of inner materials between individual *** materials from healthy mitochondria could potentially compensate for the defects found in the defective *** processes not only increase the mitochondrial number but also separate the damaged parts of mitochondria from the healthy ones,thus,facilitating the elimination of the defective mitochondria through a process known as *** fusion leads to extra connections and branching of the mitochondria,whereas extra fission results in fragmentation of *** fusion and fission processes are differently tuned in various tissues to adapt to different physiological requirements[2].

关键词： removed branching elimination

Differential function analysis: identifying structure and activation variations in dysregulated pathways

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Science China(Information sciences) 2017年第1期60卷 116-131页

作者： Chuanchao ZHANG Juan LIU Qianqian SHI Tao ZENG Luonan CHEN State Key Laboratory of Software Engineering School of Computer Wuhan University Key Laboratory of Systems Biology Innovation Center for Cell Signaling Network Institute of Biochemistry and Cell Biology Shanghai Institutes for Biological Sciences Chinese Academy of Sciences

Complex diseases are generally caused by the dysregulation of biological functions rather than individual molecules. Hence, a major challenge of the systematical study on complex diseases is how to capture the differentially regulated biological functions, e.g., pathways. The traditional differential expression analysis(DEA) usually considers the changed expression values of genes rather than functions. Meanwhile, the conventional function-based analysis(e.g., PEA: pathway enrichment analysis) mainly considers the varying activation of functions but disregards the structure change of genetic elements of functions. To achieve precision medicine against complex diseases, it is necessary to distinguish both the changes of functions and their elements from heterogeneous dysregulated pathways during the disease development and progression. In this work, in contrast to the traditional DEA, we developed a new computational framework, namely differential function analysis(DFA), to identify the changes of element-structure and expression-activation of biological functions, based on comparative non-negative matrix factorization(cN MF). To validate the effectiveness of our method, we tested DFA on various datasets, which shows that DFA is able to effectively recover the differential element-structure and differential activation-score of pre-set functional groups. In particular, the analysis of DFA on human gastric cancer dataset, not only capture the changed network-structure of pathways associated with gastric cancer, but also detect the differential activations of these pathways(i.e., significantly discriminating normal samples and disease samples), which is more effective than the state-of-the-art methods, such as GSVA and Pathifier. Totally,DFA is a general framework to capture the systematical changes of genes, networks and functions of complex diseases, which not only provides the new insight on the simultaneous alterations of pathway genes and pathway activations, but a

关键词： complex disease biological function non-negative matrix factorization network structure function activation

Diagnosing phenotypes of single-sample individuals by edge biomarkers

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Journal of Molecular cell Biology 2015年第3期7卷 231-241页

作者： Wanwei Zhang Tao Zeng Xiaoping Liu Luonan Chen Key Laboratory of Systems Biology Innovation Center for Cell Signaling NetworkInstitute of Biochemistry and Cell BiologyShanghai Institutes for Biological SciencesChinese Academy of SciencesShanghai 200031China School of life Science and Technology ShanghaiTech UniversityShanghai 201210China

network or edge biomarkers area reliable form to characterize phenotypes or ***,obtaining edges orcorrelations between molecules for an individual requires measurement ofmultiple samples of that individual,which are generally unavailable in clinical ***,it is strongly demanded to diagnose a disease by edge or network biomarkers in one-sample-for-one-individual ***,we developed a new computational framework,EdgeBiomarker,to integrate edge and node biomarkers to diagnose phenotype of each single test *** applying the method to datasets of lung and breast cancer,it reveals new marker genes/gene-pairs and related sub-networks for distinguishing earlier and advanced cancer *** method shows advantages over traditional methods:(i)edge biomarkers extracted from non-differentially expressed genes achieve better cross-validation accuracy of diagnosis than molecule or node biomarkers from differentially expressed genes,suggesting that certain pathogenic information is only present at the level of network and under-estimated by traditional methods;(ii)edge biomarkers categorize patients into low/high survival rate in a more reliablemanner;(iii)edge biomarkers are significantly enriched in relevant biological functions or pathways,implying that the association changes ina network,rather than expression changes in individual molecules,tendtobe causally related to cancer *** new frameworkof edgebiomarkers paves theway for diagnosing diseases and analyzing the irmolecular mechanisms by edges or networks in one-sample-for-one-individual *** also provides a powerful tool for precision medicine or big-data medicine.

关键词： edge biomarker edge feature progressive stages disease diagnosis big biological data

Data-based prediction and causality inference of nonlinear dynamics

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Science China Mathematics 2018年第3期61卷 403-420页

作者： Huanfei Ma Siyang Leng Luonan Chen School of Mathematical sciences Soochow University institute of Industrial Science The University of Tokyo Key Laboratory of Systems Biology Innovation Center for Cell Signaling NetworkInstitute of Biochemistry and Cell Biology Shanghai Institutes for Biological SciencesChinese Academy of Sciences

Natural systems are typically nonlinear and complex, and it is of great interest to be able to reconstruct a system in order to understand its mechanism, which cannot only recover nonlinear behaviors but also predict future dynamics. Due to the advances of modern technology, big data becomes increasingly accessible and consequently the problem of reconstructing systems from measured data or time series plays a central role in many scientific disciplines. In recent decades, nonlinear methods rooted in state space reconstruction have been developed, and they do not assume any model equations but can recover the dynamics purely from the measured time series data. In this review, the development of state space reconstruction techniques will be introduced and the recent advances in systems prediction and causality inference using state space reconstruction will be presented. Particularly, the cutting-edge method to deal with short-term time series data will be focused ***, the advantages as well as the remaining problems in this field are discussed.

关键词： nonlinear system prediction causality inference time series data

Fsh-Pc-Sce complex mediates active transcription of Cubitus interruptus （Ci）

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Journal of Molecular cell Biology 2018年第5期10卷 437-447页

作者： Xiangdong Lv Hao Chen Shuo Zhang Zhao Zhang Chenyu Pan Yuanxin Xia Jialin Fan Wenqing Wu Yi Lu Lei Zhang Hailong Wu Yun Zhao State Key Laboratory of cell Biology CAS Center for Excellence in Molecular Cell Science Innovation Center for Cell Signaling Network Shanghai Institute of Biochemistry and Cell Biology Chinese Academy of Sciences University of Chinese Academy of Sciences Shanghai 200031 China School of life Science and Technology ShanghaiTech University Shanghai 201210 China

The Hedgehog （Hh） signaling pathway plays important roles in both embryonic development and adult tissue homeostasis. Such biological functions are mediated by the transcription factor Cubitus interruptus （Ci）. Yet the transcriptional regulation of the effector Ci itself is poorly investigated. Through an RNAi-based genetic screen, we identified that female sterile （1） homeotic （Fsh）, a transcription co-activator, directly activates Ci transcription. Biochemistry assays demonstrated physical interactions among Fsh, Sex combs extra （Sce）, and Polycomb （Pc）. Functional assays further showed that both Pc and Sce are required for Ci expression, which is not likely mediated by the derepression of Engraited （En）, a repressor of Ci, in Pc or Sce mutant cells. Finally, we provide evidence showing that Pc/Sce facilitates the binding of Fsh at Ci locus and that the physical interaction between Fsh and Pc is essential for Fsh-mediated Ci transcription. Taken together, we not only uncover that Ci is transcriptionally regulated by Fsh-Pc-Sce complex but also provide evidence for the coordination between Fsh and PcG proteins in transcriptional regulation.

关键词： Ci Fsh Hedgehog polycomb complex Sce transcriptional activation

The RIP3-RIP1-NF-κB signaling axis is dispensable for necroptotic cells to elicit cross-priming of CD8^(+) T cells

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cellular & Molecular Immunology 2017年第7期14卷 639-642页

作者： Junming Ren Xian Jia Yihao Zhao Wenke Shi Jiongcong Lu Yingying Zhang Jianfeng Wu Bo Liang Rui Wu Guo Fu Jiahuai Han State Key Laboratory of cellular Stress Biology Innovation Center for Cell Signaling NetworkSchool of Life SciencesXiamen UniversityXiamen Fujian 361005China

Apoptosis and necroptosis are two types of programmed cell death with distinct morphological *** has been assumed to be more inflammatory than apoptosis,but a recent paper1 concluded that necroptotic cells cannot elicit cross-priming of CD8^(+)T cells and that NF-κB activation in necroptotic cells is required for maximal CD8^(+)T-cell cross-priming.

关键词： RIP3 priming elicit