Central control of dynamic gene circuits governs T cell rest and activation.

The ability of cells to maintain distinct identities and respond to transient environmental signals requires tightly controlled regulation of gene networks. These dynamic regulatory circuits that respond to extracellular cues in primary human cells remain poorly defined. The need for context-dependent regulation is prominent in T cells, where distinct lineages must respond to diverse signals to mount effective immune responses and maintain homeostasis.

Gene regulatory network inference from CRISPR perturbations in primary CD4 T cells elucidates the genomic basis of immune disease.

The effects of genetic variation on complex traits act mainly through changes in gene regulation. Although many genetic variants have been linked to target genes in cis, the trans-regulatory cascade mediating their effects remains largely uncharacterized. Mapping trans-regulators based on natural genetic variation has been challenging due to small effects, but experimental perturbations offer a complementary approach.

Cis-Regulatory Element and Transcription Factor Circuitry Required for Cell-Type Specific Expression of FOXP3.

FOXP3 is a lineage-defining transcription factor (TF) for immune-suppressive regulatory T cells (Tregs). While mice exclusively express FOXP3 in Tregs, humans also transiently express FOXP3 in stimulated conventional CD4+ T cells (Tconvs). Mechanisms governing these distinct expression patterns remain unknown.

A model for accurate quantification of CRISPR effects in pooled FACS screens.

CRISPR screens are powerful tools to identify key genes that underlie biological processes. One important type of screen uses fluorescence activated cell sorting (FACS) to sort perturbed cells into bins based on the expression level of marker genes, followed by guide RNA (gRNA) sequencing. Analysis of these data presents several statistical challenges due to multiple factors including the discrete nature of the bins and typically small numbers of replicate experiments.

Gene regulatory network inference from CRISPR perturbations in primary CD4+ T cells elucidates the genomic basis of immune disease.

The effects of genetic variation on complex traits act mainly through changes in gene regulation. Although many genetic variants have been linked to target genes in , the trans-regulatory cascade mediating their effects remains largely uncharacterized. Mapping trans-regulators based on natural genetic variation, including eQTL mapping, has been challenging due to small effects.

CRISPR screens decode cancer cell pathways that trigger γδ T cell detection.

γδ T cells are potent anticancer effectors with the potential to target tumours broadly, independent of patient-specific neoantigens or human leukocyte antigen background. γδ T cells can sense conserved cell stress signals prevalent in transformed cells, although the mechanisms behind the targeting of stressed target cells remain poorly characterized. Vγ9Vδ2 T cells-the most abundant subset of human γδ T cells-recognize a protein complex containing butyrophilin 2A1 (BTN2A1) and BTN3A1 (refs.

The Gastric Cancer Registry: A Genomic Translational Resource for Multidisciplinary Research in Gastric Cancer.

Background: Gastric cancer is a leading cause of cancer morbidity and mortality. Developing information systems which integrate clinical and genomic data may accelerate discoveries to improve cancer prevention, detection, and treatment. To support translational research in gastric cancer, we developed the Gastric Cancer Registry (GCR), a North American repository of clinical and cancer genomics data.