About

Yao Li is an Assistant Professor at the University of North Carolina at Chapel Hill, specializing in statistics and operations research. He completed his Ph.D. at the University of California, Davis, working with Prof. Cho-Jui Hsieh and Prof. Thomas C.M. Lee. His academic background also includes a bachelor's degree in Statistics from Fudan University, China. Dr. Li's research focuses on developing innovative algorithms to address real-world challenges within the machine learning pipeline. He investigates both the statistical and computational aspects of machine learning models, with particular emphasis on the security of these models and computational pathology.

Research topics

• Genetics
• Biology
• Medicine
• Computational biology
• Evolutionary biology
• Demography
• Endocrinology
• Bioinformatics
• Internal medicine
• Neuroscience
• Computer Science
• Radiology

Selected publications

• Preparation and theoretical calculation of lactic acid-based carbon quantum dots for Fe3+ sensing application

  Optical Materials · 2026-03-18

  article1st author
  PublisherDOI

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

  Nature · 2025-12-17 · 19 citations

  articleOpen access

  to map and analyse the 4D nucleome in widely used H1 human embryonic stem cells and immortalized fibroblasts (HFFc6). We produced and integrated diverse genomic datasets of the 4D nucleome, each contributing unique observations, which enabled us to assemble extensive catalogues of more than 140,000 looping interactions per cell type, to generate detailed classifications and annotations of chromosomal domain types and their subnuclear positions, and to obtain single-cell 3D models of the nuclear environment of all genes including their long-range interactions with distal elements. Through extensive benchmarking, we describe the unique strengths of different genomic assays for studying the 4D nucleome, providing guidelines for future studies. Three-dimensional models of population-based and individual cell-to-cell variation in genome structure showed connections between chromosome folding, nuclear organization, chromatin looping, gene transcription and DNA replication. Finally, we demonstrate the use of computational methods to predict genome folding from DNA sequence, which will facilitate the discovery of potential effects of genetic variants, including variants associated with disease, on genome structure and function.

  PublisherDOI

• MagicalRsq-X: A cross-cohort transferable genotype imputation quality metric

  UNC Libraries · 2025-10-22

  articleOpen access
  PublisherDOI

• Epigenetic reprogramming of dendritic cells by DNMT1 inhibition attenuates Th2 skewing in allergic airway inflammation

  Cell Communication and Signaling · 2025-10-24 · 1 citations

  articleOpen access

  Allergic asthma is driven by Th2-polarized immune responses, yet the epigenetic mechanisms underlying dendritic cell (DC)-mediated Th2 skewing remain unclear. Using a house dust mite (DME)-induced murine asthma model, we combined pharmacological DNMT1 inhibition (5-Aza-2′-deoxycytidine, 5-azadC), DC-specific Dnmt1 ablation (Dnmt1fl/fl Itgax-Cre mice), chromatin immunoprecipitation (ChIP), RT-qPCR, and ubiquitination assays to dissect methylation-dependent regulation of IL-12b and TIM4 in DCs. Sensitization increased DNMT1 occupancy at the Il12b promoter, inducing hypermethylation (2.5-fold vs. naïve, p < 0.001) and suppressing IL-12b expression (60% reduction, p < 0.001). DNMT1 inhibition with 5-azadC or genetic Dnmt1 ablation restored IL-12b levels (p < 0.01), reduced BALF Th2 cytokines (40–60%), eosinophils (62%), and mast cell mediators (p < 0.01), and attenuated airway inflammation. IL-12b promoted TIM4 degradation via Trim28-mediated K48-linked ubiquitination (p < 0.01), while Il12b deficiency sustained TIM4 expression and Th2 polarization. DNMT1 enrichment at the Il12b promoter correlated with TIM4 upregulation (r = 0.87, p < 0.01), forming a self-reinforcing loop disrupted by Timd4 knockdown. DNMT1 in DCs orchestrates Th2 polarization via Il12b silencing and TIM4 stabilization, positioning DNMT1 inhibitors and TIM4-targeted therapies as novel strategies to rebalance Th1/Th2 responses in asthma.

  PublisherOA PDFDOI

• Solubility behavior of diosmetin in pure and binary solvents: Thermodynamic evaluation and molecular-level interpretation

  Fluid Phase Equilibria · 2025-11-01

  article1st author
  PublisherDOI

• A genome‐wide association study of alloimmunization in the TOPMed OMG‐SCD cohort identifies a locus on chromosome 12

  UNC Libraries · 2025-10-22

  articleOpen access

  BACKGROUND: Red cell alloimmunization after exposure to donor red cells is a very common complication of transfusion for patients with sickle cell disease (SCD), resulting frequently in accelerated donor red blood cell destruction. Patients show substantial differences in their predisposition to alloimmunization, and genetic variability is one proposed component. Although several genetic association studies have been conducted for alloimmunization, the results have been inconsistent, and the genetic determinants of alloimmunization remain largely unknown. STUDY DESIGN AND METHODS: We performed a genome-wide association study (GWAS) in 236 African American (AA) SCD patients from the Outcome Modifying Genes in Sickle Cell Disease (OMG-SCD) cohort, which is part of Trans-Omics for Precision Medicine (TOPMed), with whole-genome sequencing data available. We also performed sensitivity analyses adjusting for different sets of covariates and applied different sample grouping strategies based on the number of alloantibodies patients developed. RESULTS: We identified one genome-wide significant locus on chr12 (p&thinsp;=&thinsp;3.1e-9) with no evidence of genomic inflation (lambda&thinsp;=&thinsp;1.003). Further leveraging QTL evidence from GTEx whole blood and/or Jackson Heart Study PBMC RNA-Seq data, we identified a number of potential genes, such as ARHGAP9, STAT6, and ATP23, that may be driving the association signal. We also discovered some suggestive loci using different analysis strategies. DISCUSSION: We call for the community to collect additional alloantibody information within SCD cohorts to further the understanding of the genetic basis of alloimmunization in order to improve transfusion outcomes.

  PublisherDOI

• Hi-C informed kernel association test: integrating 3-dimensional genome structure into variant-set association for whole-genome sequencing data

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-10-30

  preprintOpen access

  Variant-set association analysis is a powerful strategy for genetic studies of whole genome sequence (WGS) data, especially for rare variants. By aggregating variant signals, variant-set analysis can improve statistical power, result interpretability, and study replicability. Motivated by evidence that three-dimensional (3D) genome architecture plays a critical role in regulating gene transcription, several works have incorporated 3D genome architecture into gene-based association tests and demonstrated great promise. In this work, we extend the idea of 3D-genome guided test from gene-centric to gene-agnostic, whole-genome testing by introducing a Hi-C informed kernel association test. We present a principled procedure that converts Hi-C contact confidence into borrowing weights and integrates these weights into genetic similarity kernels so that higher-confidence interacting loci contribute more to the association test of the target variant set. We use a controlling parameter to adaptively determine the appropriate degree of information borrowing from its interacting loci during association testing. We assess the performance of the Hi-C informed test using simulations and illustrate its advantage in detecting rare-variant sets using WGS data from the ARIC study in the Trans-Omics for Precision Medicine (TOPMed) program.

  PublisherOA PDFDOI

• Abstract 4363130: Multi-Omic Analyses Identifies Novel Candidate Molecular Drivers of Coronary Artery Calcification

  Circulation · 2025-11-03

  article

  Background: Coronary artery calcification (CAC) is a strong independent predictor of CAD, yet the underlying molecular mechanisms remain incompletely understood. We aimed to identify novel molecular mediators of CAC using a multi-omics approach, with a focus on those proteins likely to have a direct effect on the vasculature. Methods: We conducted a proteome-wide association study in a pooled cohort of CARDIA, MESA, and FHS participants with Olink plasma proteomic profiling and CT-based CAC scoring (n = 6468). We identified proteins independently associated with CAC after adjusting for established CAC risk factors (age, sex, BMI, hypertension, diabetes mellitus, chronic kidney disease, statin use, ethnicity, and smoking status). These proteins were further evaluated for their ability to predict myocardial infarction in an expanded cohort of MESA, FHS, and UK Biobank participants (n=57,198). To prioritize proteins involved in vascular smooth muscle cell (VSMC)-mediated calcification, we identified proteins with differential gene expression in human VSMCs cultured in osteogenic media versus normal media. Causal effects of these proteins were evaluated using Two-sample Mendelian randomization (using inverse variance weighting (IVW), Egger and maximum likelihood) with plasma proteomics GWAS summary statistics as exposures and the largest existing CAC GWAS meta-analysis summary statistics as the outcome. Results: Of 2,805 proteins measured, 365 were independently associated with CAC scores (FDR p&lt;0.05), and enriched in pathways related to inflammatory response, immune cell signaling, ECM organization, and key vascular cell signaling pathways (Fig. 1). Among these, 216 proteins also independently predicted myocardial infarction. Transcriptomic analysis in human VSMCs identified 43 genes upregulated under osteogenic conditions, of which 8 demonstrated evidence of causal effects on CAC via Mendelian Randomization. These proteins are implicated in pathways related to immune cell signaling, bone signaling, and metabolic regulation. Conclusion: Using a multi-omics strategy integrating proteomic, transcriptomic, and genomic data, we identified several novel candidate molecular drivers of CAC with supporting evidence for their roles in myocardial infarction and VSMC osteogenic phenotypic modulation. These findings provide promising avenues for future mechanistic studies in vascular calcification.

  PublisherDOI

• Genomic loci and molecular genetic mechanisms for hidradenitis suppurativa

  UNC Libraries · 2025-11-07

  articleOpen access

  BACKGROUND: Hidradenitis suppurativa (HS) is a common, chronic, and debilitating inflammatory disease that most commonly affects intertriginous skin. Despite its high heritability, the genetic underpinnings of HS remain poorly understood. OBJECTIVE: To identify genetic signals associated with HS, determine genetic relationships with other diseases, and investigate potential molecular genetic mechanisms. METHODS: We performed a genome-wide association study meta-analysis of six studies, totaling 4,540 cases and over 1 million controls and identified genetic correlations with other common diseases. We integrated the HS data with expression quantitative trait loci from 10 trait-relevant tissues, epigenomic and transcriptomic data from human scalp, differential expression data from HS lesions versus adjacent skin, and mesenchymal Hi-C chromatin looping data. To identify functional noncoding variants, we performed transcriptional reporter assays for signals near KLF5 and SOX9. RESULTS: We identified eleven significant HS signals across seven loci: four corresponded to previously reported associations, four represented novel signals within known loci, and three were signals in newly implicated loci. We identified significant genetic correlation between HS and other inflammatory conditions, particularly inflammatory bowel disease, rheumatoid arthritis, type 2 diabetes, and asthma. We prioritized candidate genes for the 11 signals. The risk allele at KLF5 exhibited 10-fold greater transcriptional activity than the non-risk allele, while risk alleles at SOX9 showed significantly reduced transcriptional activity. CONCLUSIONS: Our results provide insights into potential genetic mechanisms underlying HS and suggest potential therapeutic targets for this challenging condition.

  PublisherDOI

• Integrating whole genome and transcriptome sequencing to characterize the genetic architecture of isoform variation

  UNC Libraries · 2025-12-04

  articleOpen access
  PublisherDOI

Recent grants

• Clinical Translational Research Center for Neurodevelopmental Disorders

  NIH · $13.6M · 2025–2027

• NIH Grant R01HL129132

  NIH · $2.7M · 2022

• Comprehensive characterization of HNF1A-driven beta-cell heterogeneity

  NIH · $3.4M · 2018–2028

• NIH Grant R01HG006703

  NIH · $931k · 2016

• NIH Grant R01HG006292

  NIH · $1.8M · 2017

Frequent coauthors

• Xin Wang

  West China Hospital of Sichuan University

  1403 shared

• Fan Yang

  Peking University

  1344 shared

• Jun Wang

  Chinese Academy of Sciences

  1307 shared

• Kai Zhang

  Second Affiliated Hospital of Harbin Medical University

  805 shared

• Myriam Fornage

  The University of Texas Health Science Center at Houston

  175 shared

• Ramachandran S. Vasan

  National Heart Lung and Blood Institute

  150 shared

• Joshua C. Bis

  University of Washington

  136 shared

• Jerome I. Rotter

  UCLA Medical Center

  131 shared