Thomas M. Norman

Host control and regulation of human anellovirus persistence

This study identifies host factors and cellular contexts governing anellovirus persistence through genomic, transcriptomic, and functional analyses.

Engineered regulatory states resolve context-dependent genetics in macular degeneration

The paper uses CRISPR activation to engineer regulatory states in RPE-1 cells, revealing hidden genetic effects in AMD by analyzing chromatin accessibility and transcriptional interactions.

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

SPP1hi macrophages in RA synovial fibrin deposits promote tissue hyperplasia.

Scaling perturbations: beyond genome-scale CRISPR screens

The paper introduces two technologies to enhance CRISPR screening, enabling large-scale genetic interaction mapping in human cells using non-fitness phenotypes.

Comprehensive transcription factor perturbations recapitulate fibroblast transcriptional states

The paper uses CRISPRa Perturb-seq to perturb transcription factors in fibroblasts, recapitulating in vivo transcriptional states and identifying key regulators.

Multiome Perturb-seq unlocks scalable discovery of integrated perturbation effects on the transcriptome and epigenome

The paper introduces Multiome Perturb-seq to simultaneously measure gene expression and chromatin accessibility in CRISPR screens, revealing regulatory programs in human cells.

Environmental challenge rewires functional connections among human genes

The paper quantifies how human gene functional connections change under environmental stress, revealing large-scale rewiring of genetic interactions across different conditions.

Maximizing CRISPRi efficacy and accessibility with dual-sgRNA libraries and optimal effectors

This paper develops compact CRISPRi sgRNA libraries and optimal effectors to improve knockdown consistency and efficiency in mammalian cells.

Mapping information-rich genotype-phenotype landscapes with genome-scale Perturb-seq

The paper performs genome-scale Perturb-seq to map genotype-phenotype relationships, uncovering new gene functions and stress-specific mitochondrial regulation.

Direct capture of CRISPR guides enables scalable, multiplexed, and multi-omic Perturb-seq

This paper introduces a method to directly capture CRISPR guides in single-cell RNA-sequencing libraries, enhancing Perturb-seq scalability and enabling multi-omic measurements.

Titrating gene expression with series of systematically compromised CRISPR guide RNAs

This paper develops a method to control gene expression using CRISPR interference and deep learning, revealing gene-specific expression-phenotype relationships.

Exploring genetic interaction manifolds constructed from rich phenotypes

The paper explores genetic interaction manifolds using rich phenotypes from Perturb-seq to classify and mechanistically understand genetic interactions.

Molecular recording of mammalian embryogenesis

The paper develops a molecular recorder to track lineage and define a mouse cell fate map using scRNA-seq, revealing transcriptional convergence of endodermal cells and estimating progenitor cell numbers.

Approaches to maximize sgRNA-barcode coupling in Perturb-seq screens

This paper identifies issues with barcode-sgRNA coupling in Perturb-seq and proposes solutions to improve accuracy in single-cell CRISPR screens.