个人简介

毕文健，北京大学基础医学院医学遗传学系课题组长，博士生导师，北京大学博雅青年学者，国家级青年高层次人才计划入选者。2010年本科毕业于四川大学数学学院，2015年博士毕业于中国科学院数学与系统科学院研究院，2015年至2018年在美国圣裘德儿童研究医院从事博士后研究，2018年至2021年在美国密歇根大学从事博士后研究，2021年6月入职北京大学基础医学院。主要工作涉及统计遗传学、生物统计与系统生物学、系统辨识与控制算法等，针对基因-环境交互作用、生存数据和多分类表型数据设计了多种快速、准确的分析算法，并应用于UK Biobank等大型生物样本库的实际数据中。以第一/通讯作者身份发表于Nature Genetics (2022), American Journal of Human Genetics (2019, 2020,2021, 2023)，Nature Communications (2025a, 2025b, 2025c), PLOS Genetics (2024), Genetics, Biostatistics等学术杂志。

个人网站

https://www.x-mol.com/groups/wenjianb

研究方向

随着高通量测序技术、高精度成像技术以及电子健康记录系统的发展，生物医学进入了健康医疗信息化的大数据新时代。海量的生物医学大数据为系统生物学研究提供了丰富的研究资源。比如英国生物样本库收集了50万英国人的健康数据并向全球科研人员开放，其中包含基因测序、脑部扫描成像、临床指标、生活方式等多维度数据。我们的研究工作涉及集值系统辨识、统计遗传学、系统生物学和生物医学大数据分析。主要包括：

1. 基于生物系统建模，并进行相关的系统辨识与控制；

2. 提出适用于生物医学大数据的统计遗传学算法；

3. 提出新的基因-环境交互作用算法；

4. 基于数据分析结果，进行实验验证和生物学机制研究

基金来源

成果及论文

*通讯作者 #共同第一作者

1. Wei Zhou#* Wenjian Bi#*, Zhangchen Zhao#, Kushal K. Dey, Karthik A. Jagadeesh, Konrad J. Karczewski, Mark J. Daly, Benjamin M. Neale, Seunggeun Lee*, Set-based rare variant association tests for biobank scale sequencing data sets. Nature Genetics, 2022, 54(10): 1466-1469.

2. Yuzhuo Ma, Yanlong Zhao, Ji-Feng Zhang, Wenjian Bi*, Efficient and accurate framework for genome-wide gene-environment interaction analysis in large-scale biobanks. Nature Communications, 2025, accepted.

3. He Xu, Yuzhuo Ma, Lin-lin Xu, Yin Li, Yufei Liu, Ying Li, Xu-jie Zhou,Wei Zhou, Seunggeun Lee, Peipei Zhang*, Weihua Yue*, Wenjian Bi*, SPAGRM: effectively controlling for sample relatedness in large-scale genome-wide association studies of longitudinal traits. Nature Communications, 2025, 16: 1413.

4. Yaoyao Sun, Yundan Liao, Yuyanan Zhang, Zhe Lu, Yuzhuo Ma, Zhewei Kang, Xiaoyang Feng, Guorui Zhao, Junyuan Sun, Yunqing Zhu, Rui Yuan, Yang Yang, Liangkun Guo, Xiao Zhang, Dai Zhang, Runsen Chen*, Wenjian Bi*, Weihua Yue*, Genome-wide interaction association analysis identifies interactive effects of childhood maltreatment and kynurenine pathway on depression.  Nature Communications, 2025, 16: 1748.

5. Wenjian Bi#, Zhiyu Xu#, Feng Liu, Zhi Xie, Hao Liu, Xiaotian Zhu, Wenge Zhong, Peipei Zhang*, Xing Tang*, Genome-wide analyses reveal the contribution of somatic variants to the immune landscape of multiple cancer type, PLOS Genetics, 2024, 1: e1011134.

6. Wenjian Bi#*, Wei Zhou#, Peipei Zhang, Yaoyao Sun, Weihua Yue, Seunggeun Lee*. Scalable mixed model methods for set-based association studies on large-scale categorical data analysis and its application to exome sequencing data in UK Biobank, American Journal of Human Genetics, 2023, 110(5): 762-773.

7. Yaoyao Sun, Yuyanan Zhang, Zhe Lu, Hao Yan, Liangkun Guo, Yundan Liao, Tianlan Lu, Lifang Wang, Jun Li, Wenqiang Li, Yongfeng Yang, Hao Yu, Luxian Lv, Dai Zhang, Wenjian Bi*, Weihua Yue*, Longitudinal Network Analysis Reveals Interactive Change of Schizophrenia Symptoms During Acute Antipsychotic Treatment. Schizophrenia Bulletin, 2022, https://doi.org/10.1093/schbul/sbac131.

8. Wenjian Bi*, Wei Zhou, Rounak Dey, Bhramar Mukherjee, Joshua N. Sampson, Seunggeun Lee*, Efficient mixed model approach for large-scale genome-wide association studies of ordinal categorical phenotypes. American Journal of Human Genetics, 2021, 108(5): 825-839.

9. Wenjian Bi, Lars G. Fritsche, Bhramar Mukherjee, Sehee Kim, Seunggeun Lee*, A fast and accurate method for genome-wide time-to-event data analysis and its application to UK-Biobank. American Journal of Human Genetics, 2020, 107(2): 222-233.

10. Wenjian Bi, Zhangchen Zhao, Rounak Dey, Lars G Fritsche, Bhramar Mukherjee, Seunggeun Lee*, A fast and accurate method for genome-wide scale phenome-wide G×E analysis and its application to UK Biobank. American Journal of Human Genetics, 2019, 105(6): 1182-1192.

11. Wenjian Bi, Yun Li, Matthew P. Smeltzer, Guimin Gao, Shengli Zhao, Guolian Kang*, STEPS: an efficient prospective likelihood approach to genetic association analyses of secondary traits in extreme phenotype sequencing. Biostatistics, 2020, 21(1): 33-49.

12. Guolian Kang#*, Wenjian Bi#, Hang Zhang, Stanley Pounds, Cheng Cheng, Sanjay Shete, Fei Zou, Yanlong Zhao, Ji-Feng Zhang, Weihua Yue*, A robust and powerful set-valued approach to rare variant association analyses of secondary traits in case-control sequencing studies. Genetics, 2017, 205(3): 1049-1062.

13. Yaoyao Sun, Yuyanan Zhang, Zhe Lu, Yundan Liao, Qidi Feng, Mingrui Yu, Yu Chen, Zhewei Kang, Xiaoyang Feng, Guorui Zhao, Junyuan Sun, Yang Yang, Liangkun Guo, Dai Zhang, Wenjian Bi, Hailiang Huang*, Weihua Yue*. Contribution of copy number variants on antipsychotic treatment response in Han Chinese patients with schizophrenia. eBiomedicine. 2024;105: 105195.

14. Yongwen Zhuang, Brooke N Wolford, Kisung Nam, Wenjian Bi, Wei Zhou, Cristen J Willer, Bhramar Mukherjee, Seunggeun Lee. Incorporating family disease history and controlling case–control imbalance for population-based genetic association studies. Bioinformatics. 2022. 38(18): 4337-4343.

15. Xiaohui Shi, Huajing Teng, Leisheng Shi, Wenjian Bi, Wenqing Wei, Fengbiao Mao*, and Zhongsheng Sun*. Comprehensive evaluation of computational methods for predicting cancer driver genes. Briefings in Bioinformatics, 2022.

16. Xiaolu Zhao#, Leisheng Shi#, Shasha Ruan#, Wenjian Bi, Yifan Chen, Lin Chen, Yifan Liu, Mingkun Li, Jie Qiao, and Fengbiao Mao. CircleBase: an integrated resource and analysis platform for human eccDNAs. Nucleic acids research, 2022, 50(D1): D72-D82.

17. Hang Zhang#, Wenjian Bi#, Yuehua Cui, Honglei Chen, Jinbo Chen, Yanlong Zhao*, Guolian Kang*, Extreme-value sampling design is cost-benefit only with valid statistical approach for exposure-secondary outcome association analyses. Statistical Methods in Medical Research, 2020, 29 (2): 466-480.

18. Guolian Kang#*, Wenjian Bi#, Yanlong Zhao*, Ji-Feng Zhang, Jun J. Yang, Heng Xu, Mignon L. Loh, Stephen P. Hunger, Mary V. Relling, Stanley Pounds and Cheng Cheng, A system identification approach to identifying genetic variants in sequencing studies for a binary phenotype, Human Heredity, 2014, 78: 104-116.

19. Wenjian Bi#, Guolian Kang#*, Yanlong Zhao, Yuehua Cui, Yun Li, Christine M Hartford, Wing Leung and Ji-Feng Zhang*, SVSI: A fast and powerful set-valued system identification approach to identifying rare variants in sequencing studies for ordered categorical traits, Annals of Human Genetics, 2015, 79: 294-309.

20. Wenjian Bi, Yanlong Zhao*, Iterative parameter estimate with batched binary-valued observations: convergence with an exponential rate, IFAC2014, 2014, 47(3): 3220-3225.

21. Hang Zhang, Wenjian Bi*, Yanlong Zhao*, Long Cheng, Set-valued system identification methods in retrospective cohort study and applications to GWAS, IFAC2017, 2017, 50(1): 1583-1588.

22. Hao Yu#, Wenjian Bi#, Chenxing Liu, Yanlong Zhao, Ji-Feng Zhang, Dai Zhang* and Weihua Yue*, Protein-interaction-network-based analysis for genome-wide association analysis of schizophrenia in Han Chinese population, Journal of Psychiatric Research, 2014, 50: 73-78.

23. Hao Yu#, Wenjian Bi#, Chenxing Liu, Yanlong Zhao, Dai Zhang and Weihua Yue*, A hypothesis-driven pathway analysis reveals Myelin-related pathways that contribute to the risk of schizophrenia and bipolar disorder, Progress in Neuro-Psychopharmacology & Biological Psychiatry, 2014, 51: 140-145.

24. Wei Zhou#*, Zhangchen Zhao#, Jonas B Nielsen, Lars G Fritsche, Jonathon LeFaive, Sarah A Gagliano Taliun, Wenjian Bi, Maiken E Gabrielsen, Mark J Daly, Benjamin M Neale, Kristian Hveem, Goncalo R Abecasis, Cristen J Willer, Seunggeun Lee*, Scalable generalized linear mixed model for region-based association tests in large biobanks and cohorts. Nature Genetics. 2020, 52: 634-639.

25. Zhangchen Zhao, Wenjian Bi, Wei Zhou, Peter VandeHaar, Lars G Fritsche, Seunggeun Lee*, UK-Biobank whole exome sequence binary phenome analysis with robust region-based rare variant test. American Journal of Human Genetics, 2020, 106(1): 3-12.

26. Yanlong Zhao*, Ting Wang, Wenjian Bi, Consensus protocol for multiagent systems with undirected topologies and binary-valued communications, IEEE Transactions on Automatic Control, 2019, 64(1): 206-221.

27. Yanlong Zhao*, Wenjian Bi and Ting Wang, Iterative parameter estimate with batched binary-valued observations. Science China Information Sciences, 2016, 59: 052201.

28. Bing Bai#, Xusheng Wang#*, Yuxin Li#, Ping-Chung Chen#, Kaiwen Yu, Kaushik Kumar Dey, Jay M. Yarbro, Xian Han, Brianna M. Lutx, Shuquan Rao, Yun Jiao, Jeffrey M. Sifford, Jonghee Han, Haiyan Tan, Timothy I. Shaw, Ji-Hoon Cho, Suiping Zhou, Hong Wang, Mingming Niu, Ariana Mancieri, Kaitlynn A. Messler, Xiaojun Sun, Zhiping Wu, Vishwajeeth Pagala, Anthony A. High, Wenjian Bi, Hui Zhang, Hongbo Chi, Vahram Haroutunian, Bin Zhang, Thomas G. Beach, Gang Yu, Junmin Peng*, Deep Multilayer Brain Proteomics Identifies Molecular Networks in Alzheimer’s Disease Progression. Neuron, 2020, 105 (6): 975-991.

29. Peng Xu, Daniel C. Scott, Beisi Xu, Yu Yao, Ruopeng Feng, Li Cheng, Kalin Mayberry, Wenjian Bi, Lance E Palmer, Moeko T. King, Hong Wang, Yuxin Li, Yiping Fan, Arno F. Alpi, Chunliang Li, Junmin Peng, James Papizan, Shondra M Pruett-Miller, Ria Spallek, Florian Bassermann, Yong Cheng, Brenda A. Schulman, Mitchell J. Weiss*, FBXO11-mediated proteolysis of BAHD1 relieves PRC2-dependent transcriptional repression in erythropoiesis. Blood, 2020, 137 (2): 155-167.

30. Miguel Ganuza, Trent Hall, David Finkelstein, Yong-Dong Wang, Ashley Chabot, Guolian Kang, Wenjian Bi, Gang Wu, Shannon McKinney-Freeman*, The global clonal complexity of the murine blood system declines throughout life and after serial transplantation. Blood, 2019, 133(18): 1927-1942.

31. Miguel Ganuza, Ashley Chabot, Xing Tang, Wenjian Bi, Sivaraman Natarajan, Robert Carter, Charles Gawad, Guolian Kang, Yong Cheng, Shannon McKinney-Freeman*, Murine hematopoietic stem cell activity is derived from pre-circulation embryos but not yolk sacs. Nature Communications, 2018, 9: 5405.

32. Mingming Niu, Ji-Hoon Cho, Kiran Kodali, Vishwajeeth Pagala, Anthony A. High, Hong Wang, Zhiping Wu, Yuxin Li, Wenjian Bi, Hui Zhang, Xusheng Wang, Wei Zou, Junmin Peng*, Extensive peptide fractionation and y1 ion-based interference detection enable accurate quantification by isobaric labeling mass spectrometry. Analytical Chemistry, 2017, 89(5): 2956-2963.

33. Latika Puri, Jonathan M Flanagan, Guolian Kang, Juan Ding, Wenjian Bi, Beth M McCarville, Ralf B Loeffler, Aaryani Tipirneni-Sajja, Martha Villavicencio, Kristine R Crews, Claudia M Hillenbrand, Jane S Hankins*, GSTM1 and liver iron content in children with sickle cell anemia and iron overload. Journal of Clinical Medicine, 2019, 8(11): 1878.