Abstract: Provided herein, in some aspects, are methods for preventing or treating diabetes in a subject, the method comprising assaying a genomic sample obtained from the subject for an intergenic variant located in a region between a C2 calcium-dependent domain containing 4A gene (C2CD4A) and a C2 calcium-dependent domain containing 4B gene (C2CD4B), and when the intergenic variant is present in the genomic sample, administering to the subject a therapy for diabetes. Also provided herein are rodent cells homozygous for a C2cd4a mutation and/or homozygous for a C2cd4h mutation, and methods for producing the rodent cells.

Abstract: The human immune system is complex, and its related diseases are similarly complicated. Therefore, human diseases, such as cancers, are often difficult to characterize and treat effectively. Immunodeficient transgenic mice for use as humanized mouse models are provided. The humanized mouse models may be further engrafted with diseased tissues or cells (e.g., human cancer cells). Methods of using the humanized mouse models to assess disease progression, immune response, and efficacy of proposed therapeutic agents are also provided herein.

Abstract: The present disclosure provides improved humanized IgG1 FCRN mouse models for use, for example, in estimating serum half-life of therapeutic proteins such as monoclonal antibodies.

Abstract: The present disclosure provides mouse models comprising an endogenous Stathmin2 (Stmn2) gene that comprises a human exon 2a polynucleotide sequence.

Abstract: Methods and apparatus for identifying alternative splicing events. The method comprises receiving a dataset of percent spliced in (PSI) values for each of a plurality of biological samples, wherein the plurality of biological samples includes a first population of samples having a first characteristic and a second population of samples having a second characteristic different from the first characteristic, fitting, to the dataset, a probabilistic model to identify clusters of samples in the dataset, calculating cluster characteristics for each of the clusters, filtering the clusters based, at least in part, on the cluster characteristics to identify a subset of clusters, each of which is associated with an alternative splicing event, and storing on the at least one storage device, information associated with the identified alternative splicing events.

Abstract: The present disclosure is directed to methods of treating clonal hematopoiesis in a subject thereof, comprising administering to the subject a mitochondria-targeted antioxidant in an amount effective to suppress clonal hematopoiesis in the subject, relative to an untreated control where the mitochondria-targeted antioxidant is a shortened form of the antioxidant ubiquinol with triphenylphosphonium.

Abstract: Provided herein are humanized mouse models and methods for determining whether administration of engineered immune cell therapies likely elicit cytokine release syndrome and/or determining the efficacy of an anti-disease therapy. Further, the models provided herein may be used to test the efficacy of different anti-CRS therapies.

Abstract: The present disclosure provides improved humanized IgG1 FCRN mouse models for use, for example, in estimating serum half-life of therapeutic proteins such as monoclonal antibodies.

Abstract: Provided herein, in some embodiments, are anti-N-glycanase 1 antibodies and methods of use.

Abstract: Genetically modified mice characterized by one or more symptoms or signs associated with expression of human APOE4p and mouse Trem2p and relevant to non-familial late-onset Alzheimer's disease are provided wherein the genome of the mouse includes: 1) a DNA sequence encoding a human APOE4 protein (APOE4p) operably linked to a promoter; and 2) a DNA sequence encoding a mouse Trem2 protein having a mutation p.R47H (Trem2p) operably linked to a promoter, such that the mouse expresses human APOE4p and mouse Trem2p. Methods are provided for screening for a compound for use in the treatment of Alzheimer's disease using such genetically modified mice.

Abstract: Humanized mouse models and methods are provided for determining whether administration of an immunomodulatory drug likely elicits a severe cytokine release syndrome in a human. Humanized mouse models and methods are also provided for determining the immunotoxicity in a human of a drug candidate or of drug combinations.

Abstract: Provided herein, in some embodiments, are anti-N-glycanase 1 antibodies and methods of use.

Abstract: Provided herein, in some embodiments, are methods for classifying the tandem duplicator phenotype of a tumor.

Abstract: Methods and apparatus for identifying alternative splicing events. The method comprises receiving a dataset of percent spliced in (PS I) values for each of a plurality of biological samples, wherein the plurality of biological samples includes a first population of samples having a first characteristic and a second population of samples having a second characteristic different from the first characteristic, fitting, to the dataset, a probabilistic model to identify clusters of samples in the dataset, calculating cluster characteristics for each of the clusters, filtering the clusters based, at least in part, on the cluster characteristics to identify a subset of clusters, each of which is associated with an alternative splicing event, and storing on the at least one storage device, information associated with the identified alternative splicing events.

Abstract: Provided herein, in some embodiments, are methods for classifying the tandem duplicator phenotype of a tumor into one of at least six TDP subtypes based on the length distribution of tandem duplications (TDs) in the genome of the tumor sample.

Abstract: Provided herein, in some aspects, is a multiplex RNA targeting system that enables live cell imaging and/or modification of multiple RNA targets. Specifically, the disclosure provides a method of live cell imaging of ribonucleic acid (RNA), or targeting RNA in a live cell, comprising: (a) delivering to a cell an RNA-editing complex that comprises a catalytically inactive Cas13 (dCas13) nuclease, a Cas 13 guide RNA (gRNA) comprising an RNA aptamer sequence, and a detectable molecule linked to an RNA-binding domain (RBD), or an RNA effector molecule linked to an RBD sequence that specifically binds to the RNA aptamer sequence; and (b) imaging the detectable molecule or RNA aptamer and RBD binding.

Abstract: Provided herein are, inter alia, compositions and methods for demethylating and methylating a target DNA sequences in a mammalian cell. The compositions and methods are, inter alia, useful for modulating the expression of a target gene, or to create a gene regulatory network.

Abstract: Humanized mouse models and methods are provided for determining whether administration of an immunomodulatory drug likely elicits a severe cytokine release syndrome in a human. Humanized mouse models and methods are also provided for determining the immunotoxicity in a human of a drug candidate or of drug combinations.

Abstract: Genetically modified mice characterized by one or more symptoms or signs associated with expression of human APOE4p and mouse Trem2p and relevant to non-familial late-onset Alzheimer's disease are provided wherein the genome of the mouse includes: 1) a DNA sequence encoding a human APOE4 protein (APOE4p) operably linked to a promoter; and 2) a DNA sequence encoding a mouse Trem2 protein having a mutation p,R47H (Trem2p) operably linked to a promoter, such that the mouse expresses human APOE4p and mouse Trem2p. Methods ace provided for screening for a compound for use in the treatment of Alzheimer's disease using such genetically modified mice.

Abstract: Humanized mouse models and methods are provided for determining whether administration of an immunomodulatory drug likely elicits a severe cytokine release syndrome in a human. Humanized mouse models and methods are also provided for determining the immunotoxicity in a human of a drug candidate or of drug combinations.