Christina S. Leslie

FourC: identifying significant and differential contacts in 1D chromatin conformation data

FourC identifies significant and differential contacts in 4C-seq data using a Bayesian model and Gaussian processes to address duplication and model spatial patterns.

scDIVA: semi-supervised integration and fine-grained annotation of tumor-immune single-cell atlases

scDIVA transfers fine-grained immune cell type annotations between tumor-immune scRNA-seq datasets by integrating batch correction and detecting novel cell states.

Developmental reversion underlies resistance to immune checkpoint blockade in kidney cancer

This study identifies developmental reversion to embryonic nephrogenesis in kidney cancer cells as a mechanism of resistance to immune checkpoint inhibitors.

Invasion status stratifies the composition of the human pancreatic cancer perineural niche

Xenium and single-nucleus profiling of 14 human pancreatic tumors shows invaded nerve neighborhoods enriched for classical cancer cells, myCAFs and lipid-handling macrophages but depleted of lymphocytes.

HiC2Self: self-supervised denoising for bulk and single-cell Hi-C contact maps

HiC2Self denoises Hi-C contact maps using self-supervised learning, reconstructing 3D chromatin structures from low-coverage data across bulk and single-cell samples.

SPP1hi macrophages in fibrin niches promote hyperplastic tissue remodeling in rheumatoid arthritis synovium

SPP1hi macrophages in RA synovial fibrin deposits promote tissue hyperplasia.

Discovery of Competent Chromatin Regions in Human Embryonic Stem Cells

The paper identifies pre-established chromatin regions in human ESCs that enable rapid activation of lineage-specific genes during differentiation.

A Genetically Engineered Human Organoid Model Reveals Distinct Genetic and Epigenetic Barriers of Lineage Plasticity in Early PDAC Transformation

This paper develops a human organoid model of early PDAC that identifies genetic and epigenetic barriers to lineage plasticity, showing CDKN2A loss is essential with KRAS/TP53 mutations and TET1 suppression links ERK signaling to transcription factor silencing.

FOXA1 mutations co-opt nascent transcription factor networks in partnership with androgen receptor to enhance prostate tumorigenicity

This study identifies FOXA1 mutations in prostate cancer, showing they alter chromatin accessibility and promote tumorigenicity by reprogramming cell fate through interactions with androgen receptor and POU2F1.

Opposing Functions of Distinct Regulatory T Cell Subsets in Colorectal Cancer

The paper identifies two distinct regulatory T cell subsets in colorectal cancer with opposing roles in tumor growth and prognosis.

Signaling induced biophysical disruption of repressed chromatin domains drives immune cell fate

The paper identifies H3 serine 28 phosphorylation as a mechanism driving chromatin derepression and immune cell fate transitions by disrupting repressive chromatin domains.

An epigenetically distinct HSC subset supports thymic reconstitution

This study identifies an epigenetically distinct HSC subset, Kitlo, that supports better thymic and T-cell reconstitution in mice and humans.

TAD hierarchy restricts poised LTR activation and loss of TAD hierarchy promotes LTR co-option in cancer

The paper shows that TAD hierarchy restricts LTR activation, and its loss in cancer allows LTRs to act as alternative promoters, driving oncogene activation and transcriptional diversity.

Discovery of NANOG enhancers and their essential roles in self-renewal and differentiation in human embryonic stem cells

The paper identifies two NANOG enhancers in human embryonic stem cells and shows their critical role in maintaining self-renewal and preventing differentiation.

Thetis cells induce food-specific Treg cell differentiation and oral tolerance

This study identifies Thetis cells IV as essential for food-specific Treg cell differentiation and oral tolerance, highlighting their distinct role from dendritic cells in immune regulation.

Deep dynamical models of single-cell multiomic velocities predict loss-of-function and rescue perturbations in B cells

Genome-wide CRISPR guide RNA design and specificity analysis with GuideScan2

GuideScan2 constructs high-specificity CRISPR gRNA databases and enables design of allele-specific gRNAs, reducing off-target effects in gene essentiality screens.

Post-mitotic transcriptional activation and 3D regulatory interactions show locus- and differentiation-specific sensitivity to cohesin depletion

This study shows that cohesin depletion affects locus- and differentiation-specific transcriptional activation and regulatory interactions in mouse ESCs, with some loops and genes being more sensitive than others.

Deep topic modeling of spatial transcriptomics in the rheumatoid arthritis synovium identifies distinct classes of ectopic lymphoid structures

The paper uses spatial transcriptomics and a new method called DeepTopics to identify distinct cellular patterns in RA synovium, revealing divergent ectopic lymphoid structures.

ChromaFold predicts the 3D contact map from single-cell chromatin accessibility

ChromaFold predicts 3D chromatin contact maps from scATAC-seq data, outperforming bulk-based methods and enabling cell-type-specific interaction analysis.

Chronic Interferon Stimulated Gene Transcription Promotes Oncogene Induced Breast Cancer

The paper shows that Mre11 deficiency leads to an ISG signature and chromatin changes, which are reversed by IFI205 ablation, promoting oncogene-induced breast cancer.

CRISPR Screening Uncovers a Long-Range Enhancer for ONECUT1 in Pancreatic Differentiation and Links a Diabetes Risk Variant

The paper identifies a long-range enhancer for ONECUT1 involved in pancreatic differentiation and links a diabetes risk variant to disrupted transcription factor binding.

Scalable sequence-informed embedding of single-cell ATAC-seq data with CellSpace

CellSpace provides a scalable sequence-informed embedding for scATAC-seq data, capturing cell subpopulations and transcription factor activity while mitigating batch effects.

An epigenetic barrier sets the timing of human neuronal maturation

Chromatin regulators including EZH2, EHMT1/2, and DOT1L establish an epigenetic barrier in human neural progenitors that poises maturation genes and sets the protracted pace of cortical neuron maturation.

An encyclopedia of enhancer-gene regulatory interactions in the human genome

ENCODE-rE2G, a classifier trained on K562 CRISPR perturbations, maps 13,455,443 enhancer-gene interactions across 352 biosamples, matching or exceeding prior models on CRISPR, eQTL, and GWAS benchmarks.

Single-cell multiome regression models identify functional and disease-associated enhancers and enable chromatin potential analysis

SCARlink predicts gene expression from chromatin accessibility in single-cell multiome data, identifies enhancers, and enables chromatin potential analysis for developmental trajectories.

Epiphany: predicting Hi-C contact maps from 1D epigenomic signals

Epiphany predicts cell-type-specific Hi-C contact maps from epigenomic signals, showing robust performance across cell types and species.

Multi-center integrated analysis of non-coding CRISPR screens

The paper reports 109 non-coding CRISPR screens analyzing 13.3Mb of the genome, identifies CRE-gene links, and provides guidelines and tools for screening non-coding regulatory elements.

BindVAE: Dirichlet variational autoencoders for de novo motif discovery from accessible chromatin

BindVAE is a deep learning method for discovering TF motifs from open chromatin data, achieving higher precision than existing methods but with lower recall.

Chromatin interaction aware gene regulatory modeling with graph attention networks

This paper introduces GraphReg, a deep learning model that uses graph attention networks to predict gene expression from epigenomic data and genomic sequences, outperforming existing methods in modeling gene regulation and identifying functional enhancers.