Ruochi Zhang

I am currently a Machine Learning Scientist at the Biology of Adversity Project at the Broad Institute.

Previously (2022–2025), I was an Eric and Wendy Schmidt Center Postdoctoral Fellow at the Broad Institute, co-advised by Prof. Bonnie Berger and Prof. Jason Buenrostro.

Before joining the Broad, I received my Ph.D. in Computational Biology from Carnegie Mellon University, advised by Prof. Jian Ma (2022). I received my Bachelor’s degree from Tsinghua University (2017).

I have broad interests in machine learning and computational biology, with a focus on developing and applying deep learning techniques for the study of epigenomics.

Papers

(†=co-first author; *=co-corresponding author)

2026

Clonal memory of colitis accumulates and promotes tumor growth

Nature, s41586-026-10258-4

Surya Nagaraja, Lety Ojeda-Miron, Ruochi Zhang, Ena Oreskovic, Yan Hu, Daniel Zeve, Karina Sharma, Roni R. Hyman, Qiming Zhang, Andrew Castillo, David T. Breault, Ömer H. Yilmaz, Jason D. Buenrostro^*
Paper

Constrained Diffusion as a Paradigm for Evolution

RECOMB 2026, accepted.

Daniel Lazarev, Anna Sappington, Grant Chau, Ruochi Zhang, Bonnie Berger^*
Paper

DANGO: Predicting higher-order genetic interactions.

Cell Systems, accepted.

Ruochi Zhang, Mihir Bafna, Jianzhu Ma^*, Jian Ma^*

2025

Engineered histones reshape chromatin in human cells

bioRxiv, doi: 10.1101/2025.09.10.674980

Siddhartha G Jena, Surya Nagaraja, Andrew S Earl, Amalia R Driller-Colangelo, Michael A Quezada, Ena Oreskovic, Max A Horlbeck, Ruochi Zhang, Wilson Gomarga, Jason D Buenrostro^*
Paper

Motif-aware Tokenization of the Genome: Towards Interpretable Modeling of Gene Regulation

NeurIPS 2025, FM4LS

Parmida Davarmanesh, Adityanarayanan Radhakrishnan, Ashia C Wilson, Ruochi Zhang, Jimin Tan, Joshua Pereira, Bo Xia^*
Paper

An integrated view of the structure and function of the human 4D nucleome.

Nature, doi: 10.1038/s41586-025-09890-3, 2025.

Job Dekker^* et al. (contributing authors)
Paper

Unified molecular approach for spatial epigenome, transcriptome, and cell lineages

PNAS, doi: 10.1073/pnas.2424070122

Yung-Hsin Huang^†, Julia A. Belk^†, Ruochi Zhang, Natasha E. Weiser, Zachary Chiang, Matthew G. Jones, Paul S. Mischel, Jason D. Buenrostro, Howard Y. Chang^*
Paper

Multi-scale footprints reveal the organization of cis-regulatory elements

Nature, s41586-024-08443-4, 2025.

Yan Hu^†, Max A. Horlbeck^†, Ruochi Zhang^†, Sai Ma, Rojesh Shrestha, Vinay K. Kartha, Fabiana M. Duarte, Conrad Hock, Rachel E. Savage, Ajay Labade, Heidi Kletzien, Alia Meliki, Andrew Castillo, Neva C. Durand, Eugenio Mattei, Lauren J Anderson, Tristan Tay, Andrew S Earl, Noam Shoresh, Charles B Epstein, Amy J. Wagers, Jason D. Buenrostro^*
Paper

2024

Degradation of IKAROS prevents epigenetic progression of T cell exhaustion in a novel antigen-specific assay

Cell Reports Medicine, 10.1016/j.xcrm.2024.101804

Tristan Tay, Gayathri Bommakanti, Elizabeth Jaensch, Aparna Gorthi, Iswarya Reddy, Yan Hu, Ruochi Zhang, Aatman Doshi, Sin Lih Tan, Verena Brucklacher-Waldert, Laura Prickett, James Kurasawa, Michael Overstreet, Steven Criscione, Jason Buenrostro, Deanna Mele^*
Paper

Expansion in situ genome sequencing links nuclear abnormalities to hotspots of aberrant euchromatin repression

bioRxiv, doi: 10.1101/2024.09.24.614614

Ajay S. Labade, Zachary D. Chiang, Caroline Comenho, Paul L. Reginato, Andrew C. Payne, Andrew S .Earl, Rojesh Shrestha, Fabiana M. Duarte, Ehsan Habibi, Ruochi Zhang, George M. Church, Edward S. Boyden, Fei Chen, Jason D. Buenrostro^*
Paper

scGHOST: Identifying single-cell 3D genome subcompartments.

Nature Methods, 21(5):814-822, 2024.

Kyle Xiong^†, Ruochi Zhang^†, Jian Ma
Paper

GAGE-seq concurrently profiles multiscale 3D genome organization and gene expression in single cells

Nature Genetics, 56(8):1701-1711, 2024.

Tianming Zhou, Ruochi Zhang, Deyong Jia, Raymond T. Doty, Adam D. Munday, Daniel Gao, Li Xin, Janis L. Abkowitz, Zhijun Duan^*, Jian Ma^*
Paper

PhyGCN: Pre-trained gypergraph convolutional neural networks with self-supervised learning.

Transactions on Machine Learning Research, 2835-8856, 2024.

Yihe Deng^†, Ruochi Zhang^†, Pan Xu, Jian Ma*, Quanquan Gu*
Paper

2023

DiffRNAFold: Generating RNA Tertiary Structures with Latent Space Diffusion

NeurIPS 2023, MLSB

Mihir Bafna, Vikranth Keerthipati, Subhash Kanaparthi, Ruochi Zhang
Paper

2022

Ultrafast and interpretable single-cell 3D genome analysis with Fast-Higashi.

Cell Systems, 13(10):798-807.E6, 2022

RECOMB 2022, 26th Annual Conference on Research in Computational Molecular Biology, 2020.

Ruochi Zhang^†,*, Tianming Zhou^†, Jian Ma*

Paper

2021

Multiscale and integrative single-cell Hi-C analysis with Higashi

Nature Biotechnology, 10.1038/s41587-021-01034-y, 2021

Ruochi Zhang, Tianming Zhou, Jian Ma.
Paper

The 3D Genome Structure of Single Cells

Annual Review of Biomedical Data Science, Vol. 4, 2021

Tianming Zhou^†, Ruochi Zhang^†, Jian Ma.
Paper

Towards the prediction of higher-order genetic interactions

RECOMB 2021, 25th Annual Conference on Research in Computational Molecular Biology, 2021.

Ruochi Zhang, Jianzhu Ma*, Jian Ma*.
Paper

SPIN reveals genome-wide landscape of nuclear compartmentalization

Genome Biology, 22:36, 2021

Yuchuan Wang, Yang Zhang, Ruochi Zhang, Tom van Schaik, Liguo Zhang, Takayo Sasaki, Daniel Peric-Hupkes, Yu Chen, David M Gilbert, Bas van Steensel, Andrew S. Belmont, Jian Ma.
Paper

2020

MATCHA: Probing multi-way chromatin interaction with hypergraph representation learning

Cell Systems, 10(5):397-407.E5, 2020.

RECOMB 2020, 24th Annual Conference on Research in Computational Molecular Biology, 2020.

Ruochi Zhang, Jian Ma.
Paper

MOCHI enables discovery of heterogeneous interactome modules in 3D nucleome

Genome Research, 30(2):227-238, 2020.

Dechao Tian^†, Ruochi Zhang^†, Yang Zhang, Xiaopeng Zhu, Jian Ma.
Paper Cover article CMU News

Hyper-SAGNN: a self-attention based graph neural network for hypergraphs

ICLR, 8th International Conference on Learning Representations, 2020.

Ruochi Zhang, Yuesong Zou, Jian Ma.
Paper

CHANGE-seq reveals genetic and epigenetic effects on CRISPR–Cas9 genome-wide activity

Nature Biotechnology, 38(11):1317-1327, 2020.

Cicera R. Lazzarotto , Nikolay L. Malinin , Yichao Li , Ruochi Zhang , Yang Yang , Yanghua He , Xin Lan , Kasey Jividen , Varun Katta , Natalia G. Kolmakova , Christopher T. Petersen , Qian Qi , Evgheni Strelcov , Samantha Maragh , Giedre Krenciute , Jian Ma , Yong Cheng , Shengdar Q. Tsai.
Paper

2018

Predicting CTCF-mediated chromatin loops using CTCF-MP

Bioinformatics, 34(13):i133–i141, 2018.

ISMB 2018. in Proceedings of the 26th Conference on Intelligent Systems for Molecular Biology.

Ruochi Zhang, Yuchuan Wang, Yang Yang, Yang Zhang, Jian Ma.
Paper

2017

Exploiting sequence-based features for predicting enhancer-promoter interactions

Bioinformatics, 33(14): i252-i260, 2017.

ISMB 2017. in Proceedings of the 25th Conference on Intelligent Systems for Molecular Biology.

Yang Yang, Ruochi Zhang, Shashank Singh, Jian Ma.
Paper F1000Prime Recommended

Awards

CMU CPCB Outstanding research accomplishment award 2020

Teaching

Teaching Assistant for Computational Genomics: School of Computer Science, Carnegie Mellon University. 01/2018 — 05/2018
Teaching Assistant for Algorithms & Advanced Data Structures: School of Computer Science, Carnegie Mellon University. 08/2018 — 12/2018
Teaching Assistant for Bioinformatics: Dragon Star Program 2017, Harbin, China. 08/2017 — 08/2017

Contact Info

Email: zhangruo@broadinstitute.org

Twitter: @RuochiZhang

Linkedin: Ruochi Zhang