Yi Zhang
Neurosurgery, Neuro-Oncology
Assistant Professor of Neurosurgery

Research Interests
Machine Learning Methods for Omics
We develop computational methods leveraging interpretable machine learning models, large-scale single-cell genomics data, and multi-omic datatypes like spatial transcriptomics and multiomics.
Multi-Cellular Tumor Microenvironment
Tumor, like many multi-cellular disease systems, are composed of multiple cell types. For solid tumor, cancer-intrinsic properties like proliferation, mutations, and epigenetic changes, and cancer-extrinsic properties like tumor-infiltrating immune cell states and inflammation, both affect tumor progression and therapeutic responses. We aim to understand molecular gene programs of tumor microenvironment (TME) cell states, pinpoint functional cancer-TME interactions, and identity targetable tumor immunity modulators. We are core members of the Brain Tumor Omics Program at Duke Preston Robert Tisch Brain Tumor Center. We will use our computational expertise to develop methods that allow us to understand the incurable tumor types and to improve cancer therapy efficacy.
Integrating Human Genetics and Functional Genomics
Human genetic variants are natural probes to investigate cell context-dependent gene regulation related to human disease. Genome-wide association studies (GWAS) identified many genetic variants associated with cancer susceptibility. We are interested in building computational methods to find cell-dependent effect of genetic variants by integrating GWAS summary statistics and functional genomics.
Bio
I am an Assistant Professor at Duke University as primary faculty in Department of Neurosurgery and secondary in Department of Biostatistics and Bioinformatics. My passion sits at the intersection of computational method development and biomedical and genomics data. I did PhD in Bioengineering at University of Illinois at Urbana-Champaign and postdoc at Dana-Farber Cancer Institute and Harvard University School of Public Health. We have been developing integrative computational genomic methods to identify functional gene regulatory mechanisms behind disease-associated human genetic variants, machine learning methods that leverage large-scale single-cell genomics data to understand cell states in tumor. My lab at Duke focuses on computational biology, bioinformatics, and machine learning in genomics. Our research interest includes developing interpretable machine learning methods for patient-based single-cell, spatial transcriptomics, and multi-omics data, and also building integrative genomics methods that combines and functional genomics, to understand multi-cellular systems like tissues and tumor microenvironment, and to finally enable translational and biomedical discoveries.
Education
- Ph.D. University of Illinois, Urbana-Champaign, 2019
Positions
- Assistant Professor of Neurosurgery
- Assistant Professor of Biomedical Engineering
- Assistant Professor in Biostatistics & Bioinformatics
- Member of the Duke Cancer Institute
Awards, Honors, and Distinctions
- EECS Rising Star 2022. University of Texas Austin. 2022
Publications
- Sun C, Zhang Y. STHD: probabilistic cell typing of single Spots in whole Transcriptome spatial data with High Definition. Cold Spring Harbor Laboratory. 2024.
- Jiang Y, Hu Z, Lynch AW, Jiang J, Zhu A, Zeng Z, et al. scATAnno: Automated Cell Type Annotation for single-cell ATAC Sequencing Data. 2024.
- Yang L, Wang J, Altreuter J, Jhaveri A, Wong CJ, Song L, et al. Tutorial: integrative computational analysis of bulk RNA-sequencing data to characterize tumor immunity using RIMA. Nat Protoc. 2023 Aug;18(8):2404u201314.
- Baur B, Shin J, Schreiber J, Zhang S, Zhang Y, Manjunath M, et al. Leveraging epigenomes and three-dimensional genome organization for interpreting regulatory variation. PLoS Comput Biol. 2023 Jul;19(7):e1011286.
- Zhang Y, Xiang G, Jiang AY, Lynch A, Zeng Z, Wang C, et al. MetaTiME integrates single-cell gene expression to characterize the meta-components of the tumor immune microenvironment. Nat Commun. 2023 May 6;14(1):2634.
- Zhang W, Roy Burman SS, Chen J, Donovan KA, Cao Y, Shu C, et al. Machine Learning Modeling of Protein-intrinsic Features Predicts Tractability of Targeted Protein Degradation. Genomics Proteomics Bioinformatics. 2022 Oct;20(5):882u201398.
- Choi YS, Erlich TH, von Franque M, Rachmin I, Flesher JL, Schiferle EB, et al. Topical therapy for regression and melanoma prevention of congenital giant nevi. Cell. 2022 Jun 9;185(12):2071-2085.e12.
- Qiu X, Boufaied N, Hallal T, Feit A, de Polo A, Luoma AM, et al. MYC drives aggressive prostate cancer by disrupting transcriptional pause release at androgen receptor targets. Nat Commun. 2022 May 13;13(1):2559.
- Zeng Z, Wong CJ, Yang L, Ouardaoui N, Li D, Zhang W, et al. TISMO: syngeneic mouse tumor database to model tumor immunity and immunotherapy response. Nucleic Acids Res. 2022 Jan 7;50(D1):D1391u20137.
- Zhang Y, Xiang G, Jiang AY, Lynch A, Zeng Z, Wang C, et al. MetaTiME: Meta-components of the Tumor Immune Microenvironment. bioRxiv. 2022.
- Zhou L, Zeng Z, Egloff AM, Zhang F, Guo F, Campbell KM, et al. Checkpoint blockade-induced CD8+ T cell differentiation in head and neck cancer responders. J Immunother Cancer. 2022 Jan;10(1).
- Wang X, Tokheim C, Gu SS, Wang B, Tang Q, Li Y, et al. Inu00a0vivo CRISPR screens identify the E3 ligase Cop1 as a modulator of macrophage infiltration and cancer immunotherapy target. Cell. 2021 Oct 14;184(21):5357-5374.e22.
- Gu S, Zhang W, Wang X, Jiang P, Traugh N, Li Z, et al. Abstract 65: Therapeutically increasing MHC-I expression potentiates immune checkpoint blockade. Cancer Research. 2021 Jul 1;81(13_Supplement):65u201365.
- Penter L, Zhang Y, Savell A, Huang T, Cieri N, Thrash EM, et al. Molecular and cellular features of CTLA-4 blockade for relapsed myeloid malignancies after transplantation. Blood. 2021 Jun 10;137(23):3212u20137.
- Gu SS, Zhang W, Wang X, Jiang P, Traugh N, Li Z, et al. Therapeutically Increasing MHC-I Expression Potentiates Immune Checkpoint Blockade. Cancer Discov. 2021 Jun;11(6):1524u201341.
- Manjunath M, Yan J, Youn Y, Drucker KL, Kollmeyer TM, McKinney AM, et al. Functional analysis of low-grade glioma genetic variants predicts key target genes and transcription factors. Neuro Oncol. 2021 Apr 12;23(4):638u201349.
- Baur B, Schreiber J, Shin J, Zhang S, Zhang Y, Manjunath M, et al. Leveraging epigenomes and three-dimensional genome organization for interpreting regulatory variation. bioRxiv. 2021.
- Qiu X, Boufaied N, Hallal T, Feit A, de Polo A, Luoma A, et al. MYC drives aggressive prostate cancer by disrupting transcriptional pause release at androgen receptor targets. bioRxiv. 2021.
- Penter L, Zhang Y, Savell A, Ranasinghe S, Huang T, Cieri N, et al. Local and Systemic Effects of Immune Checkpoint Blockade on Relapsed Myeloid Malignancies Following Allogeneic Hematopoietic Stem Cell Transplantation. Blood. 2020 Nov 5;136(Supplement 1):34u20135.
- Gu SS, Wang X, Hu X, Jiang P, Li Z, Traugh N, et al. Clonal tracing reveals diverse patterns of response to immune checkpoint blockade. Genome Biol. 2020 Oct 15;21(1):263.
- Manjunath M, Zhang Y, Zhang S, Roy S, Perez-Pinera P, Song JS. ABC-GWAS: Functional Annotation of Estrogen Receptor-Positive Breast Cancer Genetic Variants. Front Genet. 2020;11:730.
- Zhang Y, Manjunath M, Kim Y, Heintz J, Song JS. SequencEnG: an interactive knowledge base of sequencing techniques. Bioinformatics. 2019 Apr 15;35(8):1438u201340.
- Zhang Y, Manjunath M, Zhang S, Chasman D, Roy S, Song JS. Abstract 1220: Integrative genomic analysis discovers the causative regulatory mechanisms of a breast cancer-associated genetic variant. Cancer Research. 2018 Jul 1;78(13_Supplement):1220u20131220.
- Zhang Y, Manjunath M, Zhang S, Chasman D, Roy S, Song JS. Integrative Genomic Analysis Predicts Causative Cis-Regulatory Mechanisms of the Breast Cancer-Associated Genetic Variant rs4415084. Cancer Res. 2018 Apr 1;78(7):1579u201391.
- Manjunath M, Zhang Y, Yeo SH, Sobh O, Russell N, Followell C, et al. ClusterEnG: an interactive educational web resource for clustering and visualizing high-dimensional data. PeerJ Comput Sci. 2018;4.