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1.发明申请公开(公告)号：US20180100201A1
公开(公告)日：2018-04-12
申请号：US15844601
申请日：2017-12-17
申请人： The Broad Institute Inc. , Massachusetts Institute of Technology , Dana-Farber Cancer Institute, Inc. , The General Hospital Corporation
发明人： Levi A. Garraway , Benjamin Izar , Sanjay Prakadan , Aviv Regev , Orit Rozenblatt-Rosen , Alexander K. Shalek , Mario Suva , Itay Tirosh , Andrew Venteicher , Marc H. Wadsworth II , Bradley Bernstein , Anuraag Parikh , Sidharth Puram
IPC分类号： C12Q1/6886
CPC分类号： C12Q1/6886 , C12Q2600/106 , C12Q2600/112 , C12Q2600/158
摘要： This invention relates generally to compositions and methods for identifying genes and gene networks that respond to, modulate, control or otherwise influence tumors and tissues, including cells and cell types of the tumors and tissues, and malignant, microenvironmental, or immunologic states of the tumor cells and tissues. The invention also relates to methods of diagnosing, prognosing and/or staging of tumors, tissues and cells, and provides compositions and methods of modulating expression of genes and gene networks of tumors, tissues and cells, as well as methods of identifying, designing and selecting appropriate treatment regimens. The invention also relates to the modulation of complement activity to shift cellular immunity and obtain an effective therapeutic response.
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公开(公告)号：US20230000912A1
公开(公告)日：2023-01-05
申请号：US16072674
申请日：2017-01-25
申请人： THE BROAD INSTITUTE, INC. , MASSACHUSETTS INSTITUTE OF TECHNOLOGY , THE GENERAL HOSPITAL CORPORATION
发明人： Bradley Bernstein , Itay Tirosh , Mario Suva , Aviv Regev , Orit Rozenblatt-Rosen , Andrew Venteicher
IPC分类号： A61K35/17 , C12Q1/6886 , A61P35/00 , G01N33/574 , C07K16/30
摘要： This invention relates generally to compositions and methods for identifying genes and gene networks that respond to, modulate, control or otherwise influence tumors and tissues, including cells and cell types of the tumors and tissues, and malignant, microenvironmental, or immunologic states of the tumor cells and tissues. The invention also relates to methods of diagnosing, prognosing and/or staging of tumors, tissues and cells, and provides compositions and methods of modulating expression of genes and gene networks of tumors, tissues and cells, as well as methods of identifying, designing and selecting appropriate treatment regimens.
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公开(公告)号：US20200071773A1
公开(公告)日：2020-03-05
申请号：US16604651
申请日：2018-04-12
申请人： Massachusetts Eye and Ear Infirmary , The General Hospital Corporation , The Broad Institute, Inc. , Massachusetts Institute of Technology
发明人： Sidharth Puram , Itay Tirosh , Anuraag Parikh , Derrick Lin , Aviv Regev , Bradley Bernstein
IPC分类号： C12Q1/6886 , A61P35/04 , C12Q1/6837 , G16B25/10 , G16B40/00
摘要： The present invention advantageously provides for novel gene signatures, tools and methods for the treatment and prognosis of epithelial tumors. Applicants have used single cell RNA-seq to reveal novel expression programs of malignant, stromal and immune cells in the HNSCC tumor ecosystem. Malignant cells varied in expression of programs related to stress, hypoxia and epithelial differentiation. A partial EMT-like program (p-EMT) was discovered that was expressed in cells residing at the leading edge of tumors. Applicants unexpectedly linked the p-EMT state to metastasis and adverse clinical features that may be used to direct treatment of epithelial cancers (e.g., HNSCC). Applicants also show that metastases are dynamically regulated by the tumor microenvironment (TME). Finally, a computational modeling approach was developed that allows analysis of malignant cells in bulk sequencing samples.
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公开(公告)号：US20200248175A1
公开(公告)日：2020-08-06
申请号：US16758485
申请日：2018-10-23
发明人： Peter van Galen , Volker Hovestadt , Travis Hughes , Marc H. Wadsworth II , Bradley Bernstein , Alexander K. Shalek , Todd M. Gierahn , J. Christopher Love , Ang A. Tu
IPC分类号： C12N15/10 , C12Q1/6888 , C12Q1/686 , C12Q1/6886
摘要： The present invention relates to methods of deriving genetic information from RNA-seq libraries, that can enable an overlay of genetic information (such as cancer driver mutations) onto single-cell transcriptomes and permitting efficient identification, localization, and quantification of certain cells of interest within a population as well as provide low-cost selection and sequencing of any portion of a transcript, including at the 5′ end.
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公开(公告)号：US20230348899A1
公开(公告)日：2023-11-02
申请号：US18333730
申请日：2023-06-13
发明人： Peter van Galen , Volker Hovestadt , Travis Hughes , Marc H. Wadsworth II , Bradley Bernstein , Alexander K. Shalek , Todd M. Gierahn , J. Christopher Love , Ang A. Tu
IPC分类号： C12N15/10 , C12Q1/6886 , C12Q1/6888 , C12Q1/686
CPC分类号： C12N15/1065 , C12Q1/686 , C12Q1/6886 , C12Q1/6888 , C12Q2600/158
摘要： The present invention relates to methods of detecting region(s) of interest in a gene comprising a polyA tail. The region(s) of interest can include gene(s), region(s), mutation(s), deletion(s), insertion(s), indel(s), and/or translocation(s). The region(s) can be greater than or less than 1 kilobases from the polyA tail. Methods can include forming a library of single cell transcripts comprising the region(s) in close proximity to a cell barcode and a unique molecular identifier (UMI). Methods for distinguishing cells by genotype can include amplifying the transcripts using PCR methods and detecting the cell barcode and UMI using single cell sequencing methods. Transcripts can be enriched using tagged region-specific PCR primers. Cell barcodes can be brought into close proximity to the region(s) by circularizing the transcripts. Sequencing of the transcripts can include using primer binding sites added during PCR amplification and library indexes for multiplexed sequencing.
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公开(公告)号：US11732257B2
公开(公告)日：2023-08-22
申请号：US16758485
申请日：2018-10-23
发明人： Peter van Galen , Volker Hovestadt , Travis Hughes , Marc H. Wadsworth, II , Bradley Bernstein , Alexander K. Shalek , Todd M. Gierahn , J. Christopher Love , Ang A. Tu
IPC分类号： C12P19/34 , C12N15/10 , C12Q1/686 , C12Q1/6886 , C12Q1/6888
CPC分类号： C12N15/1065 , C12Q1/686 , C12Q1/6886 , C12Q1/6888 , C12Q2600/158
摘要： The present invention relates to methods of detecting region(s) of interest in a gene comprising a polyA tail. The region(s) of interest can include gene(s), region(s), mutation(s), deletion(s), insertion(s), indel(s), and/or translocation(s). The region(s) can be greater than or less than 1 kilobases from the polyA tail. Methods can include forming a library of single cell transcripts comprising the region(s) in close proximity to a cell barcode and a unique molecular identifier (UMI). Methods for distinguishing cells by genotype can include amplifying the transcripts using PCR methods and detecting the cell barcode and UMI using single cell sequencing methods. Transcripts can be enriched using tagged region-specific PCR primers. Cell barcodes can be brought into close proximity to the region(s) by circularizing the transcripts. Sequencing of the transcripts can include using primer binding sites added during PCR amplification and library indexes for multiplexed sequencing.
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公开(公告)号：US20190284603A1
公开(公告)日：2019-09-19
申请号：US15754222
申请日：2016-08-19
IPC分类号： C12Q1/6806 , G01N33/68
摘要： The present invention provides for single-molecule profiling of combinatorial protein modifications and single-molecule profiling of combinatorial protein modifications combined with single-molecule sequencing of protein/nucleic acids complexes. High-throughput single-molecule imaging was applied to decode combinatorial modifications on millions of individual nucleosomes from pluripotent stem cells and lineage-committed cells. Applicants identified bivalent nucleosomes with concomitant repressive and activating marks, as well as other combinatorial modification states whose prevalence varies with developmental potency. Applying genetic and chemical perturbations of chromatin enzymes show a preferential affect on nucleosomes harboring specific modification states. The present invention also combines this proteomic platform with single-molecule DNA sequencing technology to simultaneously determine the modification states and genomic positions of individual nucleosomes. This novel single-molecule technology can be used to address fundamental questions in chromatin biology and epigenetic regulation leading to novel therapeutics and diagnostics.
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公开(公告)号：US20230272452A1
公开(公告)日：2023-08-31
申请号：US17989296
申请日：2022-11-17
IPC分类号： C12Q1/6806 , G01N33/68 , C12Q1/68
CPC分类号： C12Q1/6806 , G01N33/6878 , C12Q1/68
摘要： The present invention provides for single-molecule profiling of combinatorial protein modifications and single-molecule profiling of combinatorial protein modifications combined with single-molecule sequencing of protein/nucleic acids complexes. High-throughput single-molecule imaging was applied to decode combinatorial modifications on millions of individual nucleosomes from pluripotent stem cells and lineage-committed cells. Applicants identified bivalent nucleosomes with concomitant repressive and activating marks, as well as other combinatorial modification states whose prevalence varies with developmental potency. Applying genetic and chemical perturbations of chromatin enzymes show a preferential affect on nucleosomes harboring specific modification states. The present invention also combines this proteomic platform with single-molecule DNA sequencing technology to simultaneously determine the modification states and genomic positions of individual nucleosomes. This novel single-molecule technology can be used to address fundamental questions in chromatin biology and epigenetic regulation leading to novel therapeutics and diagnostics.
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公开(公告)号：US11479805B2
公开(公告)日：2022-10-25
申请号：US15754222
申请日：2016-08-19
IPC分类号： C12Q1/6806 , G01N33/68 , C12Q1/68
摘要： The present invention provides for single-molecule profiling of combinatorial protein modifications and single-molecule profiling of combinatorial protein modifications combined with single-molecule sequencing of protein/nucleic acids complexes. High-throughput single-molecule imaging was applied to decode combinatorial modifications on millions of individual nucleosomes from pluripotent stem cells and lineage-committed cells. Applicants identified bivalent nucleosomes with concomitant repressive and activating marks, as well as other combinatorial modification states whose prevalence varies with developmental potency. Applying genetic and chemical perturbations of chromatin enzymes show a preferential affect on nucleosomes harboring specific modification states. The present invention also combines this proteomic platform with single-molecule DNA sequencing technology to simultaneously determine the modification states and genomic positions of individual nucleosomes. This novel single-molecule technology can be used to address fundamental questions in chromatin biology and epigenetic regulation leading to novel therapeutics and diagnostics.
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公开(公告)号：US11339442B2
公开(公告)日：2022-05-24
申请号：US16061546
申请日：2016-12-14
IPC分类号： C12Q1/6886
摘要： The present application generally to the diagnosis and treatment of diseases resulting from the alteration of chromatin boundaries between topologically-associated domains. In particular, the present application relates to detection of mutations causing DNA hypermethylation phenotypes, CpG methylation within CTCF binding motifs, and aberrant gene expression caused by altered chromatin topology. Applicants show that IDH mutant gliomas exhibit hyper-methylation at CTCF binding sites, compromising binding of this methylation-sensitive insulator protein. Applicants also demonstrate that loss of CTCF at a domain boundary permits a constitutive enhancer to aberrantly interact with the receptor tyrosine kinase gene PDGFRA, a prominent glioma oncogene. Thus, Applicants have uncovered that IDH mutations may promote gliomagenesis by disrupting chromosomal topology and allowing aberrant regulatory interactions that induce oncogene expression.
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