个人简介

郑小琪，上海交通大学医学院教授，博士生导师，单细胞组学与疾病研究中心生物信息学平台主任。主要从事医学人工智能和生物信息学领域的研究，在单细胞及空间转录组的统计建模和算法开发、生物医学大模型构建等方面上取得了一系列研究成果。以第一或通讯作者在Genome Biology, Genome Research, Nucleic Acids Research, Bioinformatics, PLoS Computational Biology, PNAS 等杂志累计发表SCI论文80余篇。主持上海市人才发展基金，以负责人承担国家自然科学基金面上项目3项，青年项目1项，以项目骨干承担国家重点研发计划专项2项。现任中国工业与应用数学学会（CSIAM）数学生命科学分会常务理事、中国生物信息学会生物信息学算法专委会常委委员、上海市毒理学会副秘书长、中国计算机学会生物信息专业委员会执行委员等。

研究方向

1. 空间组学算法开发

空间组学技术在解析高通量分子图谱的同时保留了细胞的原位物理坐标，为揭示复杂组织的精细结构与微环境异质性带来了颠覆性变革。然而如何从海量、高噪且高度稀疏的时空多维数据中精准挖掘生物学规律，是当前亟待解决的核心计算难题。本方向融合统计建模与前沿人工智能技术，致力于空间组学算法体系的开发，包括开发空间数据从头模拟方法、高维数据特征提取与降维框架、复杂微环境下的细胞空间互作分析、多维度的空间扰动响应分析等。

2. 医学人工智能模型开发

多模态生物医学大数据的通用大模型开发及其在垂直领域的应用，如单细胞与空间组学大模型、生理信号与多模态临床大模型等。

代表性论文（#：第一作者，*：通讯作者）

[1] Jiang WJ, Cai K, Sun Y, Liu A, Zhu H, Gao R, Zhong C, Wei N, Lai F, Fei T, Wang YJ, Zheng X* Xu M*, Wu HJ*: Harmonizing single-cell 3D genome data with STARK and scNucleome. Genome Biology 2026, 27.

[2] Hu C, Wei N, Yang J, Wu H-J*, Zheng X*: STCC: consensus clustering enhances spatial domain detection for spatial transcriptomics data. Genome Research 2025, 35:1415-1428.

[3] Yang J, Wang L, Liu L, Zheng X*: GraphPCA: a fast and interpretable dimension reduction algorithm for spatial transcriptomics data. Genome Biology 2024, 25 (1), 287.

[4] Zheng X#*, Zhang N#, Wu HJ, Wu H*: Estimating and accounting for tumor purity in the analysis of DNA methylation data from cancer studies. Genome Biology 2017, 18:17.

[5] Zheng X#*, Zhong S: From structure to function, how bioinformatics help to reveal functions of our genomes. Genome Biology 2017, 18:183.

[6] Zheng X#, Zhao Q#, Wu H-J#, Li W, Wang H, Meyer CA, Qin QA, Xu H, Zang C, Jiang P, Li F, Hou Y, He J, Wang J, Wang J, Zhang P*, Zhang Y*, Liu XS*: MethylPurify: tumor purity deconvolution and differential methylation detection from single tumor DNA methylomes. Genome Biology 2014, 15:419.

[7] Yang J, Wei N, Qu Y, Hu C, Zhang W, Liu L, Wu HJ, Zheng X*: Spider: a flexible and unified framework for simulating spatial transcriptomics data. Bioinformatics 2026, 42(1), btaf562.

[8] Hu C, Li Y, Li Y, Zhang N*, Zheng X*: BS-clock, advancing epigenetic age prediction with high-resolution DNA methylation bisulfite sequencing data. Bioinformatics 2024, 40 (11), btae656.

[9] Jiang WJ, Hu C, Lai F, Pang W, Yi X, Xu Q, Wang H, Zhou J, Zhu H, Zhong C, Kuang Z, Fan R, Shen J, Zhou X, Wang YJ, Wong CCL*, Zheng X*, Wu HJ*: Assessing base-resolution DNA mechanics on the genome scale. Nucleic Acids Research 2023, 51(18):9552-9566.

[10] Wei N, Nie Y, Liu L*, Zheng X*, Wu HJ*, Secuer: Ultrafast, scalable and accurate clustering of single-cell RNA-seq data, PLoS Computational Biology 2022, 18(12): e1010753.

[11] Ding Y, Cai K, Liu L, Zhang Z, Zheng X*, Shi J*, mHapTk: a comprehensive toolkit for the analysis of DNA methylation haplotypes, Bioinformatics. 2022, 38(22):5141-5143.

[12] Zhang Z#, Dan Y#, Xu Y, Zhang J, Zheng X*, Shi J*: The DNA methylation haplotype (mHap) format and mHapTools, Bioinformatics 2021, 37 (24):4892-4894.

[13] Zhang W#, Li Z, Wei N, Wu H-J, Zheng X*: Detection of differentially methylated CpG sites between tumor samples with uneven tumor purities. Bioinformatics 2020, 36(7), 2017-2024.

[14] Zhang W#, Feng H#, Wu H*, Zheng X*, Accounting for Tumor purity improves cancer subtype classification from DNA methylation data, Bioinformatics 2017, 33(17), 2651–2657.

[15] Zhang N#, Wu HJ#, Zhang W, Wang J, Wu H*, Zheng X*: Predicting tumor purity from methylation microarray data. Bioinformatics 2015, 31:3401-3405.

[16] Qin Y#, Zhang W#, Sun X, Nan S, Wei N, Wu HJ, Zheng X*: Deconvolution of heterogeneous tumor samples using partial reference signals. PLoS Computational Biology 2020, 16(11): e1008452.

[17] Gao S, Zhu H, Cai K, Liu L, Zhang Z, Ding Y, Xu Y, Zheng X*, Shi J*: TRAmHap: accurate prediction of transcriptional activity from DNA methylation haplotypes in bisulfite-sequencing data. Briefings in Bioinformatics. 2023, 24(4):bbad214.

[18] Wu T, Dai Y, Xu Y, Zheng J, Chen S, Zhang Y, Tian P, Zheng X*, Wang H*: ExosomePurity: tumour purity deconvolution in serum exosomes based on miRNA signatures. Briefings in Bioinformatics. 2023, 24(3):bbad119.

[19] Chaoyue Xu, Wanxing Xu, Yushun Yuan, Xiaoqing Chen, Ouyang Mo, Zhe Yin, Xinhua Huang, Yuanyuan Wang, Lingfei Hu, Wenwen Xue, Yun Zou, Luyao Zhang, Kunlin Li, Yueru Tian, Jihong Liu, Sichu Xiong, Lei Wu, Yanmei Dong, Guangsheng Chen, Yuping Zhang, Zili Zhou, Ming Guan, Xiaotian Huang, Zhiyi He, Lin Zhong, Lingbing Zeng, Pei Hao*, Xiaoqi Zheng*, Changbin Chen*, Ning-Ning Liu*, Dongsheng Zhou*: Global Stress Responses Identify the Functionally Divergent Regulators Required for Candida auris Commensalism andPathogenicity. Exploration 2025, 0:20240482.

[20] Wang Y, Zhang S, Yang X, Hwang JK, Zhan C, Lian C, Wang C, Gui T, Wang B, Xie X, Dai P, Zhang L, Tian Y, Zhang H, Han C, Cai Y, Hao Q, Ye X, Liu X, Liu J, Cao Z, Huang S, Song J, Pan-Hammarstrom Q, Zhao Y, Alt FW, Zheng X, Da LT, Yeap LS, Meng FL: Mesoscale DNA feature in antibody-coding sequence facilitates somatic hypermutation. Cell 2023, 186:2193-2207 e2119.

[21] Liu NN, Yi CX, Wei LQ, Zhou JA, Jiang T, Hu CC, Wang L, Wang YY, Zou Y, Zhao YK, Zhang LL, Nie YT, Zhu YJ, Yi XY, Zeng LB, Li JQ, Huang XT, Ji HB, Kozlakidis Z, Zhong L, Heeschen C, Zheng XQ, Chen C, Zhang P, Wang H: The intratumor mycobiome promotes lung cancer progression via myeloid-derived suppressor cells. Cancer Cell 2023, 41, 1927-1944.

[22] Niu B#, Paulson JN, Zheng X, Kolter R*: Simplified and Representative Bacterial Community of Maize Roots. P Natl Acad Sci USA 2017, 114 (12): E2450-E2459.

[23] Hu X, Zhang J, Wang J, Fu J, Li T, Zheng X, Wang B, Gu S, Jiang P, Fan J, Carroll, MC, Wucherpfennig K, Hacohen N, Zhang F, Zhang P, Liu JS*, Li B*, Liu XS*: Widespread B cell clonal expansions and related mechanism of immune evasion in human cancers, Nature Genetics 2019, 51(3):560-567.

[24] Huang ME, Qin Y, Shang Y, Hao Q, Zhan C, Lian C, Luo S, Liu LD, Zhang S, Zhang Y, et al: C-to-G editing generates double-strand breaks causing deletion, transversion and translocation. Nature Cell Biology 2024, 26:294-304.

[25] Liu X, Liu T, Shang Y, Dai P, Zhang W, Lee BJ, Huang M, Yang D, Wu Q, Liu LD, Zheng X, Zhou BO, Dong J, Yeap LS, Hu J, Xiao T, Zha S, Casellas R, Liu XS, Meng FL: ERCC6L2 promotes DNA orientation-specific recombination in mammalian cells, Cell Research 2020, 30 (9), 732-744.

[26] Dai P, Tan Y, Luo Y, Liu T, Huang Y, Shang Y, Huang ME, Liu X, Zhang S, Wang Y, et al: Transcription-coupled AID deamination damage depends on ELOF1-associated RNA polymerase II. Molecular Cell 2025, 85:1280-1295 e1289.

[27] Fan H#, Lv P#, Huo X, Wu J, Wang Q, Cheng L, Liu Y, Tang Q, Zhang L, Zhang F, Zheng X, Wu H, Wen B*: The nuclear matrix protein HNRNPU maintains 3D genome architecture globally in mouse hepatocytes, Genome Research 2018, 28:192-202.

[28] Ni T#, Li XY#, Lu N#, An T, Liu ZP, Fu R, Lv WC, Zhang YW, Xu XJ, Grant Rowe R, Lin YS, Scherer A, Feinberg T, Zheng XQ, Chen BA, Liu XS, Guo QL, Wu ZQ*, Weiss SJ*: Snail1-dependent p53 repression regulates expansion and activity of tumour-initiating cells in breast cancer. Nature Cell Biology 2016, 18:1221-1232.

[29] T Xu, X Zheng, B Li, P Jin, Z Qin, H Wu: A comprehensive review of computational prediction of genome-wide features, Briefings in bioinformatics 2020, 21(1), 120-134.

[30] Wang J#, Zheng X*: Comparison of protein secondary structures based on backbone dihedral angles. Journal Theoretical Biology 2008, 250:382-387.