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公开(公告)号：US12141963B2
公开(公告)日：2024-11-12
申请号：US17282039
申请日：2019-10-04
Applicant: THE ROCKEFELLER UNIVERSITY
Inventor： Jakob Metzger , Fred Etoc , Ali Brivanlou , Eric Siggia
IPC: G06T7/62 , C12N5/0735 , G01N1/30 , G01N33/50 , G06F18/21 , G06F18/214 , G06N3/084 , G06T7/00 , G06V10/764 , G06V10/82 , G06V20/69 , G16B40/00
Abstract: Systems and methods for identifying molecules that are biologically active against a disease, where the method can comprise culturing a first mammalian cell population under organoid formation conditions in the presence of a test molecule to obtain a first organoid, wherein the first mammalian cell population, when cultured under the organoid formation conditions in the absence of the test molecule, results in an organoid with a disease phenotype; imaging the first organoid following exposure to the test molecule; analyzing one or more images of the first organoid using a neural network that has been trained to assign a probability score of disease or non-disease ranging between 0% and 100%; assigning the first organoid a probability score ranging between 0% and 100%; wherein the test molecule is biologically active against the disease if the probability score of the first organoid is greater than a cutoff probability score of non-disease or lower than a cutoff probability score of disease.
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公开(公告)号：US11674952B2
公开(公告)日：2023-06-13
申请号：US16079755
申请日：2017-02-24
Applicant: The Rockefeller University
Inventor： Ali Brivanlou , Albert Ruzo , Alessia Deglincerti , Tomomi Haremaki , Fred Etoc
IPC: C12Q1/02 , G01N33/50 , C12Q1/18 , C12N15/09 , C12N5/0735 , A61K31/506 , A61K45/06 , C07K14/47
CPC classification number: G01N33/5073 , A61K31/506 , A61K45/06 , C07K14/47 , C12N5/0606 , C12N15/09 , C12Q1/02 , C12Q1/025 , C12Q1/18 , C12N2503/02 , C12N2510/00
Abstract: Compositions and methods disclosed concern an isogenic population of in vitro human embryonic stem cells comprising a disease form of the Huntingtin gene (HTT) at the endogenous HTT gene locus in the genome of the cell; wherein the disease form of the HTT gene comprises a polyQ repeat of at least 40 glutamines at the N-terminus of the Huntingtin protein (HTT). The cell lines of the disclosure comprise genetically-defined alterations made in the endogenous HTT gene that recapitulate Huntington's Disease in humans. Furthermore, the cell lines have isogenic controls that share a similar genetic background. Differentiating cell lines committed to a neuronal fate and fully differentiated cell lines are also provided and they also display phenotypic abnormalities associated with the length of the polyQ repeat of the HTT gene. These cell lines are used as screening tools in drug discovery and development to identify substances that fully or partially revert these phenotype abnormalities.
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公开(公告)号：US20210372994A1
公开(公告)日：2021-12-02
申请号：US17282039
申请日：2019-10-04
Applicant: THE ROCKEFELLER UNIVERSITY
Inventor： Jakob Metzger , Fred Etoc , Ali Brivanlou , Eric Siggia
Abstract: Systems and methods for identifying molecules that are biologically active against a disease, where the method can comprise culturing a first mammalian cell population under organoid formation conditions in the presence of a test molecule to obtain a first organoid, wherein the first mammalian cell population, when cultured under the organoid formation conditions in the absence of the test molecule, results in an organoid with a disease phenotype; imaging the first organoid following exposure to the test molecule; analyzing one or more images of the first organoid using a neural network that has been trained to assign a probability score of disease or non-disease ranging between 0% and 100%; assigning the first organoid a probability score ranging between 0% and 100%; wherein the test molecule is biologically active against the disease if the probability score of the first organoid is greater than a cutoff probability score of non-disease or lower than a cutoff probability score of disease.
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