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 methods and compositions for the treatment of Charcot-Marie-Tooth disease, comprising an inhibitor of a GCN2 pathway component.

Abstract: Provided herein, in some aspects, are compositions and methods for artificially modulating alternative splicing, for example, inducing exon inclusion and/or exon exclusion events. In some embodiments, a catalytically inactive programmable nuclease, such as dCasRx, is fused to an RNA-binding protein (or fragment or isoform thereof) and, when guided to a target of interest by a specific guide RNA (gRNA), can regulate alternative splicing in eukaryotic cells.

Abstract: Methods and apparatus for providing clinical decision support. The method comprises receiving phenotype information for a patient, determining a likelihood ratio for each of the phenotype features included in the received phenotype information with respect to each of a plurality of diseases, determining, based on the likelihood ratio for each of the phenotype features, a composite likelihood ratio for each of the plurality of diseases, ranking the plurality of diseases based, at least in part, on the determined composite likelihood ratios, and displaying at least some of the ranked plurality of diseases.

Abstract: Provided herein, in some embodiments, are methods, compositions, and kits for treating lapatinib-resistant gastric cancer.

Abstract: Provided herein, in some embodiments, are methods for modulating expression and/or activity of disks large-associated protein 2 (DLGAP2), as well as methods of treating age-related cognitive decline, such as Alzheimer's disease.

Abstract: Provided herein, in some embodiments, are human patient-derived brain tumor models and methods of use.

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: In certain embodiments, this present invention provides antibodies and Fc fusion proteins with enhanced pharmacokinetics, such as biotinylated antibodies or biotinylated Fc fusion polypeptides.

Abstract: Provided herein, in some embodiments, are methods, compositions, and systems for identifying alternatively spliced tumor-specific exon inclusion and exclusion events that can be used for survival prognosis.

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 invention, in part, relates to ChIA-Drop methods, which comprise methods of drop-based sequencing.

Abstract: The present disclosure provides a genetically modified mouse comprising a genomic nucleic acid encoding human APOE4, a genomic nucleic acid encoding mouse TREM2 modified to include a R47H substitution, and at least one genomic modification selected from the group consisting of: (a) a genomic nucleic acid encoding mouse ABCA7 modified to include an A 1541 G substitution; (b) a genomic nucleic acid encoding mouse APP modified to include G601R, F606Y, and R609H substitutions; (c) a genomic nucleic acid encoding mouse PLCG2 modified to include a M28L substitution; (d) a genomic nucleic acid encoding mouse MTHFR modified to include a A262V substitution; (e) an inactivated Ceacam1 allele; and (f) an inactivated Il1rap allele. Methods of producing the genetically modified mouse and methods of using the genetically modified mouse are also provided.

Abstract: The present disclosure, in some embodiments, provides sequence detection systems (sequence detectors) for the detection of specific nucleotides sequences present in the genome of live cells (e.g., single live cells) to achieve, for example, in vivo and in situ imaging, cell selection, and/or cell ablation.

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

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 are compositions, methods, and kits for anticancer therapies using a glycolytic inhibitor and a RAD51 complex inhibitor.

Abstract: Modeling human disease in cultured cells requires efficient modification of one or both alleles depending on dominant or recessive inheritance. Editing of single nucleotide variants (SNVs) is particularly challenging because the modified allele contains only one mismatch relative to the target sequence and is subject to re-cleavage and damage by the nuclease. The donor nucleic acids provided herein are, inter alia, useful for editing genome sequences by introducing precise changes in a target site in the presence of the donor sequence and minimizing re-cleavage of the donor nucleic acid by nucleases. By doing so, the compositions and methods provided herein produce modified genomic sequences resistant to nuclease cleavage.

Abstract: Provided herein are methods and tools for targeting detecting (e.g., imaging) extrachromosomal DNA, for example, in cancer cells.

Abstract: Described herein are methods and compositions relating to the treatment of e.g., cancer, autoimmune disease, immune deficiency, and/or neurodegenerative disease. In some embodiments, the methods of treatment relate to administering a compound as described herein. In some embodiments, the subject treated according to the methods described herein is a subject determined to have an increased level of DNA damage.