Regeneron Pharmaceuticals, Inc.

Wen Fury

Yu Bai

Brian Zambrowicz

Matthew Koss

Marine Prissette

Jamie M Orengo

Jeanne Allinne

Karthikeyan Swaminathan

Cas-protein-ready tau biosensor cells, CRISPR/Cas synergistic activation mediator (SAM)-ready tau biosensor cells, and methods of making and using such cells to screen for genetic modifiers of tau seeding or aggregation are provided. Reagents and methods for sensitizing such cells to tau seeding activity or tau aggregation or for causing tau aggregation are also provided.

CRISPR/Cas screening platform to identify genetic modifiers of tau seeding or aggregation

Methods and systems for CRISPR positive selection are described. CRISPR positive selection uses DNA sequencing to identify genes that their perturbation by CRISPR guide RNAs is correlated to the phenotype. In some aspects, disclosed are genome-wide CRISPR/Cas9 screening methods to identify genetic modifiers. Also disclosed are the apparatuses used for performing the methods.

Methods and systems for CRISPR selection

Provided herein are methods for accurately determining the alleles present at a locus that is broadly applicable to any locus, including highly polymorphic loci such as HLA loci, BGA loci and HV loci. Embodiments of the disclosed methods are useful in a wide range of applications, including, for example, organ transplantation, personalized medicine, diagnostics, forensics and anthropology.

High resolution allele identification

The present invention relates to the identification of certain biomarkers for use in identifying patients who have, or are likely to develop an IL-33 mediated disease or disorder and who are more likely to respond to therapy with an IL-33 antagonist. The invention also relates to methods of treatment of an IL-33-mediated disease or disorder in a patient by administering an IL-33 antagonist to the patient in need thereof and monitoring the effectiveness of therapy using the biomarkers described herein. Also provided are methods for decreasing the level of at least one biomarker in a subject suffering from an IL-33-mediated disease or disorder, and methods for treating such diseases or disorders according to the expression levels of one or more biomarkers. The methods of the present invention comprise administering to a subject in need thereof a pharmaceutical composition comprising an interleukin-33 antagonist.

Biomarkers related to interleukin-33 (IL-33)-mediated diseases and uses thereof

Methods, software, and systems are provided for determining the probability of an overlap set of entities having an overlap size, where the overlap set is independently selected from two sets of non-identical entities. Applications of the invention to microarrays are provided. Probability distributions are provided for determining the probability that the size of an overlap gene set from two different microarrays occurs by chance. Microarray analysis for determining the size of a statistically significant overlap gene set given two different microarrays is described. Overlap set size probability determinations that account for the total number of genes in two different microarrays and not just the common genes are described.

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New York, NY, United States of America

Wen Fury