Abstract: The embodiments disclosed herein utilized RNA targeting effectors to provide a robust CRISPR-based diagnostic with attomolar sensitivity. Embodiments disclosed herein can detect both DNA and RNA with comparable levels of sensitivity and can differentiate targets from non-targets based on single base pair differences. Moreover, the embodiments disclosed herein can be prepared in freeze-dried format for convenient distribution and point-of-care (POC) applications. Such embodiments are useful in multiple scenarios in human health including, for example, viral detection, bacterial strain typing, sensitive genotyping, and detection of disease-associated cell free DNA.

Abstract: The present invention provides for methods and compositions for treating cancer. Disclosed are novel tumor biomarkers and therapeutic targets. Also disclosed are CAR T cells targeting tumor specific surface proteins. Also disclosed are shared expression programs specific to tumor cells.

Abstract: The present invention provides for a human cell atlas of the colon from healthy and diseased subjects. The atlas was obtained by single sequencing of about 117,000 cells. The present invention discloses novel markers for cell types. Moreover, genes associated with disease are identified in the colon and colon specific cell types. The invention provides for diagnostic assays based on gene markers and cell composition, as well as target cell types that express genes associated with disease. Finally, disclosed are novel cell types and methods of quantitating, detecting and isolating the cell types.

Abstract: Described herein are methods for suppressing an immune response in a subject, e.g., a subject with an autoimmune disease, by administering to the subject a therapeutically effective amount of recombinant CD5L, CD5L homodimers and/or CD5L:p40 heterodimers, or nucleic acids encoding any of these. Also described are methods for enhancing an immune response in a subject, e.g., a subject with cancer, infection, or an immune deficiency, by administering to the subject a therapeutically effective amount of an antibody or antigen-binding fragment thereof that binds specifically to CD5L, D5L homodimers and/or CD5L:p40 heterodimers, and inhibits their binding to the IL-23 receptor, or inhibits formation of the CD5L homodimer and/or CD5L:p40 heterodimer, or inhibitory nucleic acids that target CD5L and/or p40.

Abstract: The subject matter disclosed herein is generally directed to novel CD8+ and CD4+ T cell subtypes associated with effector, suppressive or regulatory T cell functions. Moreover, the subject matter disclosed herein is generally directed to methods and compositions for use of the subtype. Also, disclosed herein are gene signatures and markers associated with the subtype and use of said signatures and markers. Further disclosed are therapeutic methods of using said gene signatures and immune cell subtype. Further disclosed are pharmaceutical compositions comprising populations of CD4+ and/or CD8+ TILs or populations of immune cells depleted for a specific subtype. Further disclosed are interactions with other T cell subtypes.

Abstract: The present invention relates to methods for high multiplex protein or cellular constituent analysis in single cells or single isolated aggregations of cellular constituents. The methods provide for embedding cells or isolated aggregations of cellular constituents in a hydrogel mesh and labeling of cellular constituents with labeling ligands linked to a nucleic acid tag. Cellular constituents can be determined using sequencing methods.

Abstract: Embodiments disclosed herein provide methods of using somatic mutations in mitochondrial genomes to retrospectively infer cell lineages in native contexts and to serve as genetic barcodes to measure clonal dynamics in complex cellular populations. Further, somatic mutations in mitochondrial DNA (mtDNA) are tracked by single cell genomic approaches for simultaneous analysis of single cell lineage and state. Applicants further show that mitochondrial mutations can be readily detected with contemporary single cell transcriptomic and epigenomic technologies to concomitantly capture gene expression profiles and chromatin accessibility, respectively.

Abstract: The application relates to proteome analysis in single cells. Specifically, disclosed are high throughput methods of detecting proteins in single cells using barcoding, aptamers and single cell sequencing. Solid supports used in recording the cell-of-origin of target proteins and target proteins expressed in the cell-of-origin are disclosed. Additionally, methods of detecting proteins and mRNA in single cells are disclosed. Additionally, methods of detecting protein interactions are disclosed. Additionally, methods of detecting post translationally modified proteins in single cells are disclosed. The application also relates to solid supports or beads and methods of producing said solid supports or beads for use in the described methods.

Abstract: Described herein are methods and uses thereof for in vivo evaluating functions of multiple genes in parallel by combining in utero genetic perturbation of progenitor cells and single-cell transcriptomic profiling of progeny cells in animals. These methods can be used, among other things, to reveal in vivo gene functions in a cell type-specific manner.

Abstract: The present invention provides methods and tools for analyzing genetic interactions. The subject matter disclosed herein is generally directed to single cell genomics and proteomics. In one embodiment provided is a method of cell and nuclei hashing using sample barcodes. In another embodiment are method of performing genomewide CRISPR perturbation screens.

Abstract: Described herein are agonists of CD5L monomer, CD5L:CD5L homodimer, and CD5L:p40 heterodimer and compositions and methods for modulating or suppressing an immune response in a subject, e.g. a subject with an autoimmune disease, involving said agonists.

Abstract: Described herein are methods for suppressing an immune response in a subject, e.g., a subject with an autoimmune disease, by administering to the subject a therapeutically effective amount of recombinant CD5L, CD5L homodimers and/or CD5L:p40 heterodimers, or nucleic acids encoding any of these. Also described are methods for enhancing an immune response in a subject, e.g., a subject with cancer, infection, or an immune deficiency, by administering to the subject a therapeutically effective amount of an antibody or antigen-binding fragment thereof that binds specifically to CD5L, D5L homodimers and/or CD5L:p40 heterodimers, and inhibits their binding to the IL-23 receptor, or inhibits formation of the CD5L homodimer and/or CD5L:p40 heterodimer, or inhibitory nucleic acids that target CD5L and/or p40.

Abstract: The present invention provides novel pan-cancer T cell exhaustion regulators. CXCR6 expressed in CD8+ T cells was specifically identified as regulating anti-tumor immunity. Modulating CXCR6-CXCL16 interaction is useful in modulating anti-tumor immunity. The identified genes may be modulated in T cells for use in adoptive cell transfer. The identified genes may be modulated in vivo.

Abstract: The subject matter disclosed herein is generally directed to a novel CD8+ T cell subtype associated with suppressive or regulatory T cell functions. Moreover, the subject matter disclosed herein is generally directed to methods and compositions for use of the subtype. Also, disclosed herein are gene signatures and markers associated with the subtype and use of said signatures and markers. Further disclosed are therapeutic methods of using said gene signatures and immune cell subtype. Further disclosed are pharmaceutical compositions comprising populations of CD8+ TILs depleted for a specific subtype. Further disclosed are interactions with other T cell subtypes.

Abstract: Computational and functional analysis identified the neuropeptide receptor Nmur1 as selectively expressed on Type 2 innate lymphoid cells (ILC2s). While both IL-33 and IL-25 promote ILC activation in vivo, IL-33 induces robust ILC proliferation, whereas ILCs activated with IL-25 do not proliferate as robustly and up-regulate Nmur1 expression. Treatment with neuromedin U (NMU), the neuropeptide ligand of Nmur1, had little effect on its own. Co-administration of IL-25 with NMU, however, dramatically amplified allergic lung inflammation and induced the proliferation and expansion of specific ILC2 subsets, characterized by a molecular signature unique to pro-inflammatory ILC2s. The results demonstrate that Nmur1 signaling strongly modulates IL-25-mediated ILC2 responses, resulting in highly proliferative pro-inflammatory ILCs, and highlights the importance of neuro-immune crosstalk in allergic inflammatory responses at mucosal surfaces.

Abstract: Provided herein are methods and compositions for identifying ionocytes from respiratory epithelial cells, and uses of such cells for treatment of inflammatory lung disease. Also provided herein are methods and compositions for modulating respiratory tract epithelial cell proliferation, differentiation, maintenance, and/or function.

Abstract: The present invention is generally directed to identify interacting cells in the tumor microenvironment and using the identified interactions to enhance anti-tumor immunity in cancer. Identified interactions can be modulated using therapeutic agents. Immune cells resistant to suppression can be used for adoptive cell transfer. The present invention is also generally directed to cell types and genes that are correlated to time of tumor growth and tumor size.

Abstract: The subject matter disclosed herein is generally directed to tissue specific modulation of Th17 differentiation and pathogenicity by targeting tissue specific Th17 gene programs and gene targets. The tissue specific modulation may be used therapeutically to treat a disease or condition in the tissue where it arises. The subject matter disclosed herein is also directed to detecting tissue specific Th17 cells for diagnostic and therapeutic methods.

Abstract: The subject matter disclosed herein is generally directed to modulating anti-tumor T cell immunity by modulating steroidogenesis. Steroidogenesis may be modulated with inhibitors of enzymes that synthesize glucocorticoids in a tumor. The inhibitor may target Cyp11a1. The inhibitor may be metyrapone. The invention further relates to modulating immune states, such as CD8 T cell immune states, in vivo, ex vivo and in vitro. The invention further relates to diagnostic and screening methods.

Abstract: The present invention is generally directed to using a single cell atlas for identifying genes and gene programs that are associated with a phenotype (e.g., disease phenotypes or traits). The present invention is also generally directed to identifying interacting genetic variants using a single cell atlas as a prior for selecting variants for testing. The single cell atlas is used for constructing gene modules. Interactions are tested within and between modules. Applicants identified genetic variants that can be used to identify pathways and cell types important for IBD risk. Moreover, genetic variants were identified that can be used as therapeutic targets.