Abstract: The present disclosure provides methods and systems for mapping gene and protein expression in a cell (i.e., mapping gene and protein expression within the same cell simultaneously). The present disclosure also provides methods for diagnosing a disease or disorder (e.g., a neurological disorder such as Alzheimer's disease) in a subject. Methods of screening for a candidate agent capable of modulating gene and/or protein expression are also provided by the present disclosure. The present disclosure also provides methods for treating a disease or disorder, such as Alzheimer's disease, in a subject in need thereof. A plurality of oligonucleotide probes, which may be useful for performing the methods described herein, are also described by the present disclosure, as well as kits comprising any of the oligonucleotide probes described herein.

Abstract: Computer-implemented methods, computer program products, and systems determine an omics profiles of a cell using microscopy imaging data. In one aspect, a computer-implemented method determines an omics profiles of a cell using microscopy imaging data by a) receiving microscopy imaging data of a cell or a population of cells; b) determining a targeted expression profile of a set of target genes from the microscopy imaging data using a first machine learning model, the target genes identifying a cell type or cell state of interest; and c) determining a single-cell omics profile for the population of cells using a second machine learning algorithm model. The targeted expression profile and a reference single-cell RNA-seq data set are used as inputs for the second machine learning model.

Abstract: The present invention features improved compounds, especially methods of identifying patients having cancer using biomarkers (e.g., PDE3A, SLFN12 and/or CREB3L1) that correlate with drug sensitivity and consequently treating a stratified patient population with an agent of the invention (e.g., Compounds 1-6 disclosed herein).

Abstract: A way to design a codebook for estimating the type of a molecule at a particular location in a fluorescence microscopy image makes use of one or both of (1) knowledge of the non-uniform prior distribution of molecule types (i.e., some types are known a priori to occur more frequently than others) and/or knowledge of co-occurrence of molecule types at close locations (e.g., in a same cell); and (2) knowledge of a model of the (e.g., random) process that yields the intensities that are expected at a location when a molecule with a particular subset of markers (i.e., a molecule of a type that has been assigned a codeword that defines that subset) is present at that location. The codebook design may provide experimental efficiency by reducing the number of images that need to be acquired and/or improve classification or detection accuracy by making the codewords for different molecule types more distinctive.

Abstract: Embodiments disclosed herein provide methods, systems, and computer program products that utilize long-range phase information to detect subtle chromosome imbalances in genotype data. Clonal expansions result from mutation followed by selective proliferation, and the embodiments disclosed herein may be used to somatic structural variant events (SVs) predictive or diagnostic of cancer and other diseases.

Abstract: The present disclosure provides methods of treating and/or preventing osteoporosis using salt-inducible kinase (SIK) inhibitors. Also provided are methods of using SIK inhibitors for increasing the function of osteocytes, increasing the number of osteoblasts, increasing the activity of osteoblasts, inhibiting the resorption of a bone, decreasing the number of osteoclasts, inhibiting the activity of osteoclasts, increasing the mass of a bone, down-regulating the expression of the gene SOST, and/or inhibiting the activity of sclerostin. The SIK inhibitors may be combined with Src inhibitors or CSF1R inhibitors.

Abstract: Disclosed and claimed are mutation(s) or modification(s) of the CRISPR enzyme, for example a Cas enzyme such as a Cas9, which obtain an improvement, for instance a reduction, as to off-target effects of a CRISPR-Cas or CRISPR-enzyme or CRISPR-Cas9 system or complex containing or including such a mutated or modified Cas or CRISPR enzyme or Cas9. Methods for making and using and uses of such mutated or modified Cas or CRISPR enzyme or Cas9 and systems or complexes containing the same and products from such methods and uses are also disclosed and claimed.

Abstract: The present disclosure relates to compositions, methods and kits for enhancing ribosomal activities in a host cell, especially improvement of the translation activity of heterologous ribosomes within a host cell. Specifically, the instant disclosure provides a number of evolved rRNA sequences, which were remarkably identified to possess enhanced translation activities, improved orthogonal-ribosome binding site (o-RBS) and orthogonal anti-ribosome binding site (o-antiRBS) sequences, host cells possessing deletion or disruption of ribosome hibernation promoting factor (HPF) that thereby exhibit enhanced propagation of selection phage constructs during (PACE), among other aspects. New transgenic organisms harboring heterologous ribosomes and operons are also provided.

Abstract: The present invention relates to in vivo methods for modeling tumor formation and/or tumor evolution comprising the use of eukaryotic cells in which one or more genetic target locus has been altered by the CRISPR/Cas system, and which cells are transplanted in non-human eukaryote as a model system for tumor formation and tumor evolution. In particular in vivo genetic screening methods for identifying genes involved in tumorigenesis and metastasis are disclosed. The invention further relates to kits and components for practicing the methods, as well as materials obtainable by the methods, in particular tumor and metastasis samples and cells or cell lines derived therefrom. The invention also relates to diagnostic and therapeutic methods derived from the information obtained in the modeling methods.

Abstract: The disclosure provides molecular classifiers for use in the characterization and diagnosis of lung cancer and methods of selecting and treating subjects with appropriate personalized cancer treatments, including but not limited to CDK4/6 inhibitors, c-Met inhibitors, PD-1/PD-L1 inhibitors and combinations thereof.

Abstract: The invention provides for systems, methods, and compositions for targeting nucleic acids. In particular, the invention provides non-naturally occurring or engineered DNA or RNA-targeting systems comprising a novel DNA or RNA-targeting CRISPR effector protein and at least one targeting nucleic acid component like a guide RNA.

Abstract: Compositions and methods are provided herein for conducting prime editing of a target DNA molecule (e.g., a genome) that enables the incorporation of a nucleotide change and/or targeted mutagenesis. The compositions include fusion proteins comprising nucleic acid programmable DNA binding proteins (napDNAbp) and a polymerase (e.g., reverse transcriptase), which is guided to a specific DNA sequence by a modified guide RNA, named an PEgRNA. The PEgRNA has been altered (relative to a standard guide RNA) to comprise an extended portion that provides a DNA synthesis template sequence which encodes a single strand DNA flap which is synthesized by the polymerase of the fusion protein and which becomes incorporated into the target DNA molecule.

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: Compounds of formula (I), processes for their production and their use as pharmaceuticals are described herein.

Abstract: The present disclosure provides methods for treating cancer in a subject (by inhibiting e.g., APOBEC3A, APOBEC3B, or REV1), and methods of diagnosing cancer in a subject. Methods of tracking mutagenesis induced by a gene of interest (e.g., APOBEC3A, APOBEC3B, or REV1) and methods of screening for inhibitors and synthetic lethalities are also described herein. Further provided by the present disclosure are cell lines and antibodies for use in the methods described herein.

Abstract: The invention features pseudotyped viral particles (e.g., lentiviral or gammaretroviral particles) and compositions and methods of use thereof, where the viral particles comprise a VHH domain.

Abstract: The invention provides for systems, methods, and compositions for targeting nucleic acids. In particular, the invention provides non-naturally occurring or engineered DNA-targeting systems comprising a novel DNA-targeting CRISPR effector protein and at least one targeting nucleic acid component like a guide RNA Methods for making and using and uses of such systems, methods, and compositions and products from such methods and uses are also disclosed and claimed.

Abstract: Compounds, pharmaceutical compositions, and methods of use of said compounds and pharmaceutical compositions for treating or preventing a microbial infection or for inducing antimicrobial activity against a microbial infection.

Abstract: The present disclosure provides methods and systems for profiling RNAs being translated in a cell. Also provided by the present disclosure are methods for diagnosing a disease or disorder in a subject based on a profile of the RNAs being translated in a cell, including cells within an intact tissue. Methods of screening for or testing a candidate agent capable of modulating translation of one or more RNAs are also provided by the present disclosure. The present disclosure also provides methods for treating a disease or disorder in a subject in need thereof. Pairs of probes and sets of probes comprising oligonuclcotide portions, which may be useful for performing the methods described herein, are also described by the present disclosure. Additionally, the present disclosure provides kits comprising any of the probes described herein.

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.