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Sequence-to-function modeling uncovers the context-specific grammar of Drosophila chromatin insulation

Chromatin is organized into self-interacting topologically associating domains partitioned by boundary elements that insulate adjacent domains and restrict regulatory interactions. Yet, how sequence context and combinations of factors dictate …

Discovery of Tcf7 regulators with clonally-resolved CRISPR screens identifies Trim28 as a mediator of CD8 T cell differentiation in tumors

Stem-like TCF7+ CD8 T cells sustain anti-tumor responses and support immune checkpoint blockade. We systematically identified regulators of this cell state using genome-wide CRISPR screens in primary T cells in vitro. Using random barcodes to link …

Shared binding sites for the chromosomal architectural protein Su(Hw) mediate physical interactions between Drosophila TAD boundaries

Loop extrusion has been clearly shown to be insufficient as a mechanism to explain TAD formation, leaving a large gap in our understanding of how the specificity of TAD boundary interactions and inter-TAD chromosomal interactions are determined. Many …

A community machine learning challenge to predict the effects of gene perturbations on T cell differentiation for cancer immunotherapy

Perturbations of genes with functional importance in T cells could be used to change the distribution of CD8 T cell states to enhance anti-tumor functions for cancer immunotherapies. We launched a world-wide computational challenge to predict the …

Benchmarking cell type deconvolution in spatial transcriptomics and application to cancer immunotherapy

Cell type deconvolution is essential for resolving multicellular composition in spatial transcriptomics data, yet the accuracy and consistency of current methods across biological contexts remain uncertain. We introduce a benchmarking framework using …

Single-cell multiomics reveals archetypal regulatory programs shared across CD4 and CD8 T cell subsets in viral infection

T cells protect against pathogens and tumors and can differentiate into various functionally distinct subsets. While each subset exhibits a characteristic epigenomic and transcriptional profile, essential immune functions such as self-renewal, …

Autophagy Suppresses CCL2 to Preserve Appetite and Prevent Lethal Cachexia

Macroautophagy (autophagy hereafter) captures intracellular components and delivers them to lysosomes for degradation and recycling. In adult mice, autophagy sustains metabolism to prevent wasting by cachexia and to survive fasting, and also …