Abstract: The present disclosure relates to systems and method of determining transcriptomic profile from omics imaging data. The systems and methods train machine learning methods with intrinsic and extrinsic features of a cell and/or tissue to define transcriptomic profiles of the cell and/or tissue. Applicants utilize a convolutional autoencoder to define cell subtypes from images of the cells.

Abstract: The invention relates to gene expression profiles and signatures of CAR T cells. The invention provides methods and compositions of CAR T cells and populations. The invention provides assays and methods of screening subjects to assess efficacy and safety of CAR T cell treatments and therapies. The invention provides assays and methods of engineering and/or administering CAR T cells to promote efficacy and safety.

Abstract: The present invention relates to DNA 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 sequence-components which may identify the targeted sequences-of-interest themselves and/or spatial beacons relative to which their distances are measured.

Abstract: Interleukin (IL)-33 is a critical regulator of allergic airway inflammation in the lung and is released by stressed or damaged epithelial cells. Here, Applicants show that alveolar macrophages regulate epithelial alarmin expression via CLEC-2 (C-type Lectin-like Receptor-2), which binds to PDPN (podoplanin). Therefore, CLEC-2/PDPN interactions are critical for regulating type 2 immunity in the lung and modulating expression of the epithelial alarmin IL-33. Methods are disclosed for therapeutic and screening applications. Novel therapeutic targets in alveolar macrophages and epithelial cells are disclosed.

Abstract: The present invention provides novel compositions and methods based on the discovery of the mechanisms and gene expression programs associated with synovial sarcoma. In particular, core oncogenic programs were expressed by a distinct subpopulation of malignant cells and associated with poor clinical outcome, a cell cycle program distinguished cycling from non-cycling cells, with cycling cells having a tendency to be poorly differentiated and indicative of increased risk of metastatic disease, and a (de)differentiation program that can identify poorly differentiated cells, the absence of which was prognostic of metastasis free survival. Methods of treatment include use of HDAC and CDK4/6 inhibitors to block oncogenic program to selectively target synovial sarcoma cells. Finally, macrophages and T cells can mimic the effect of SS18-SSX inhibition by secreting TNFa and IFNg, which allows for adoptive cell therapy to provide cells with increased expression of TNFa and IFNg.

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: The subject matter disclosed herein is generally directed to modulation of Th17 differentiation and pathogenicity by use of metabolic targets. The metabolic targets are the molecules of the polyamine pathway or glycolysis pathway. Modulation of the polyamine pathway can shift Th17 pathogenicity and shift the transcriptome of Th17 cells to a Treg or Th1 transcriptome. The polyamine analogue DFMO can be used to modulate an inflammatory response. Inhibitors of enzymes in the glycolysis pathway can shift Th17 pathogenicity.

Abstract: The present invention provides novel compositions and methods based on the discovery of the mechanisms and gene expression programs associated with homeostatic ILC2s and proinflammatory ILC2s that drive tissue inflammation. Immune signaling abnormalities in the small intestine can trigger chronic type 2 inflammation. Applicants analyzed 58,067 immune cells from the mouse small intestine by single-cell RNA-seq at steady state and after induction of a type 2 inflammatory reaction to ovalbumin. Cell type composition and cell programs shifted in response to inflammation, especially in ILC2s. A key transcript in the inflammation-induced program in intestinal KLRG1+ILC2s was exon 5 of Calca, encoding the alpha-calcitonin gene-related peptide (a-CGRP). a-CGRP antagonized IL-25-induced activation of intestinal ILC2s and reduced their frequency in an ovalbumin reaction model. ?-CGRP activated a cAMP response, which suppressed ILC2 proliferation.

Abstract: The present disclosure relates to systems and method of in-situ tissue profiling. Methods for spatiotemporal processing of a sample, capturing molecules of interest, and correlating cells in the sample to the capture molecules are provided.

Abstract: The present invention is generally directed to identifying genes and cell types that are correlated with tumor progression in the tumor microenvironment. PENK was identified as a therapeutic target that is positively correlated with tumor time and size. Targeting PENK can enhance anti-tumor immunity. Opioid signaling can be modulated to enhance anti-tumor immunity. The present invention is also generally directed to 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.

Abstract: Described in several embodiments herein are engineered phagemids and bacteriophages containing the same. Also described in several embodiments herein are methods of using the engineered phagemids and bacteriophages containing the same. In some embodiments, the engineered phagemids and bacteriophages containing the same are capable of providing multi-omic information at the single-cell level.

Abstract: Disclosed herein are polypeptides and compositions comprising one or more neoantigens, methods of identifying neoantigens, and methods for preparing a neoantigen for an immunogenic pharmaceutical composition. The neoantigen can be specific to a subject that has a cancer, disease, or other disorder.

Abstract: The present invention provides for methods, systems and computer products for aligning single cell data with spatial data to generate spatial maps of cell types and gene expression at single cell resolution. The invention further provides for mapping to common coordinate frameworks.

Abstract: The present disclosure relates to systems and method of in-situ tissue profiling. Methods for spatiotemporal processing of a sample, capturing molecules of interest, and correlating cells in the sample to the capture molecules are provided.

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 of identifying cell types and cell subtypes from a biological sample or population of target cells. The methods further provide for determining cell type or cell subtype signatures. The method further provides for bipolar cell subtypes and markers and cell signatures thereof.

Abstract: Methods of targeting CD58 signaling to enhance antitumor immunity and overcome resistance to checkpoint blockade therapy. Gene signatures associated with immune fitness were identified. Markers and therapeutic targets for such immunotherapy resistance.

Abstract: The present invention provides tools and methods for the systematic analysis of genetic interactions, including higher order interactions. The present invention provides tools and methods for combinatorial probing of cellular circuits, for dissecting cellular circuitry, for delineating molecular pathways, and/or for identifying relevant targets for therapeutics development.

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: Techniques Nuc-seq, Div-Seq, and Dronc-Seq are allow for unbiased analysis of any complex tissue. Nuc-Seq, a scalable single nucleus RNA-Seq method, can sensitively identify closely related cell types, including within the adult hippocampus. Div-seq combines Nuc-Seq with EdU-mediated labeling of proliferating cells, allowing tracking of transcriptional dynamics of newborn neurons in an adult neurogenic region in the hippocampus. Dronc-Seq uses a microfluidic device to co-encapsulate individual nuclei in reverse emulsion aqueous droplets in an oil medium together with one uniquely barcoded mRNA-capture bead.