Abstract: A cell atlas of the Choroid Plexus is provided and includes novel markers for cell types. Novel cell types and methods of quantitating, detecting and isolating the cell types are disclosed. Methods of treatment, including for oxidative stress in the brain are provided, as well as methods for controlling differentiation, maintenance and/or function of the cell types disclosed herein.

Abstract: This invention relates generally to compositions and methods for identifying the regulatory network that modulates, controls or otherwise influences dendritic cell (DC) response(s), for example, dendritic cell maturation, dendritic cell antiviral response(s) and/or dendritic cell inflammatory response(s), as well compositions and methods for exploiting the regulatory network that modulates, controls or otherwise influences dendritic cell response(s) in a variety of therapeutic and/or diagnostic indications.

Abstract: Described herein are compositions and methods of using single-cell RNA-sequencing to identify treatment resistance in patients with ovarian cancer. Also, described herein are compositions and methods for treatment targeting resistance in patients with ovarian cancer.

Abstract: The subject matter disclosed herein is generally directed to compositions and methods for treating diffuse gliomas with histone H3 lysine27-to-methionine mutations (H3K27M-gliomas). Disclosed herein are gene signatures specific for tumor cell types and compositions for treatment of H3K27M gliomas. In one embodiment, PRC1 is targeted in a treatment regimen for H3K27M-gliomas.

Abstract: The present disclosure provides compositions, systems, and methods for pooled screening of perturbations correlating to a phenotype. The present disclosure also provides for methods of in vivo perturbation screening. The present disclosure also provides for high-throughput sample multiplexing. The present disclosure also provides for methods to determine the clonal effects associated with millions of genetic perturbation combinations using standard pooled screening reagents.

Abstract: The subject matter disclosed herein is generally directed to detecting and modulating novel gene signatures for the treatment and prognosis of cancer. The novel gene signatures predict overall survival in cancer and can be targeted therapeutically. Specifically, disclosed is a resistance program identified by a comprehensive single-cell profiling study in melanoma patients, which was validated in two large validation cohorts. Using a large-scale in silico prediction, CDK4/6 inhibitors were identified as a class of drugs that may reverse this resistance program. These predictions were validated in melanoma cell lines, patient-derived co-culture models, and melanoma in vivo models, which show that the combination of abemaciclib and immune checkpoint blockade (ICB) overcome intrinsic drug resistance. The present invention provides for detecting an immunotherapy resistance signature and modulating the signature with CDK4/6 inhibition.

Abstract: This invention relates generally to compositions and methods for identifying the regulatory network that modulates, controls or otherwise influences T cell balance, for example, Th17 cell differentiation, maintenance and/or function, as well compositions and methods for exploiting the regulatory network that modulates, controls or otherwise influences T cell balance in a variety of therapeutic and/or diagnostic indications. This invention also relates generally to identifying and exploiting target genes and/or target gene products that modulate, control or otherwise influence T cell balance in a variety of therapeutic and/or diagnostic indications.

Abstract: The present invention provides methods and tools for analyzing genetic interactions. The subject matter is generally directed to single-cell genomics and proteomics, including methods of performing genome-wide CRISPR perturbation screens and determining gene expression phenotypes.

Abstract: Provided herein include methods and compositions for analyzing nucleic acid in individual cells. In some embodiments, the methods herein include generating, within individual cells, fragmented cellular genomic DNA and cDNA copies of cellular RNA molecules, barcoding the fragmented genomic DNA and the cDNA within each cell such that the genomic DNA and the cDNA from the same cell receive the same unique barcode sequence, isolating the barcoded genomic DNA and cDNA, and characterizing one or more features of the individual cells based, at least in part, on sequencing of the isolated barcoded genomic DNA and the cDNA.

Abstract: Methods and compositions for producing induced pluripotent stem cell by introducing nucleic acids encoding one or more transcription factors including Obox6 into a target cell.

Abstract: The present invention discloses novel methods, compositions, and uses thereof for removing or overcoming immunosuppression. More specifically, the methods and compositions disclosed herein target effector Treg cells by modulating ST2 and/or IL-33 signaling using pharmaceutical inhibitors and/or genetic ablation, whereby the levels and/or activities of effector Treg cells in a tumor microenvironment are inhibited, and the infiltration of effector CD8+ cytotoxic T cells into tumor microenvironment increases. As a result, tumor growth is inhibited and tumor volume is reduced. The present invention also provides methods for identifying and isolating effector Treg cells in a population of heterogeneous cells.

Abstract: Described herein are signatures that characterize a particular stromal cell state, type, and/or subtype. In some embodiments, the signatures can characterize a dysfunctional stromal cell. In some embodiments, the signatures can be used to diagnose, treat, and/or prevent a disease. In some embodiments, the signatures can characterize remodeling in a bone marrow microenvironment. Also described herein are cell populations having a specific signature and modulated cells that can be modulate to have a specific signature.

Abstract: The present invention provides methods for introducing mutations to primary cells and selecting for the mutations to obtain a population of cells for modeling cancer. Such methods may comprise at least one round of introducing one or more mutations into one or more cells in a population of cells in vitro and culturing the cells until the mutation(s) are positively selected in the population. The cells may be cultured in vitro. The cells may be cultured in vivo. In certain embodiments, the cells are positively selected in vivo in order to select for cells capable of evading the immune system. In certain embodiments, cells are selected in an immune competent animal model. The cells may primary cells. The population of cells may be used for drug screening and for studying cancer.

Abstract: The subject matter disclosed herein is generally directed to detecting and modulating novel gene signatures for the treatment and prognosis of cancer. The novel gene signatures predict overall survival in cancer and can be targeted therapeutically.

Abstract: Described herein are antagonists of CD5L monomer, CD5L:CD5L homodimer, and CD5L:p40 heterodimer and compositions and methods for modulating or enhancing an immune response in a subject, e.g. a subject with cancer or chronic infection, involving said antagonists.

Abstract: The present invention relates to molecular microscopy or volumetric imaging by proximal unique molecular identifiers (“UID”) reaction (“VIPUR”) microscopy methods to record the cellular co-localization and/or spatial distributions of arbitrary nucleic acid sequences, or other biomolecules tagged with nucleic sequences. The method involves one or both of two DNA sequence-components such as an ?-UID, which may identify the targeted sequences-of-interest themselves and/or spatial beacons relative to which their distances are measured, and a- ?-UID, which labels ?-UID association events.

Abstract: The present invention relates to tissue and cell imaging utilizing genomic informatics and gene-expression profiling. Gene-expression profiles utilized in methods to obtain in situ imaging of cells and tissues provide complex molecular fingerprints regarding the relative state of a cell or tissue.

Abstract: The subject matter disclosed herein is generally directed to novel CD8+ tumor infiltrating lymphocyte (TIL) subtypes associated with response to immunotherapy treatment. Specifically, the subtypes are associated with checkpoint blockade therapy. Moreover, the subject matter disclosed herein is generally directed to methods and compositions for use of the subtypes. Also, disclosed herein are gene signatures and markers associated with the subtypes and use of said signatures and markers. Further disclosed are therapeutic methods of using said gene signatures and immune cell subtypes. Further disclosed are pharmaceutical compositions comprising populations of CD8+ TILs enriched for a specific subtype.

Abstract: The subject matter disclosed herein is generally directed to methods and compositions for modulating inflammation driven by differentiation of quiescent tissue-resident ILCs into a spectrum of pathogenic effectors. The subject matter disclosed herein is also generally directed to detecting and monitoring an ILC response. Additionally, the subject matter is directed to treating skin inflammation, such as psoriasis.

Abstract: This invention relates generally to compositions and methods for modulating complement component 3 (C3) activity or expression to treat, control or otherwise influence tumors and tissues, including cells and cell types of the tumors and tissues, and malignant, microenvironmental, or immunologic states of the tumor cells and tissues. The invention also relates to methods of diagnosing, prognosing and/or staging of tumors, tissues and cells.