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公开(公告)号：US20210124904A1
公开(公告)日：2021-04-29
申请号：US17137317
申请日：2020-12-29
申请人： Peter Keith Rogan , Yanxin Li , Jin Liu
发明人： Peter Keith Rogan , Yanxin Li , Jin Liu
摘要： Automation of microscopic pathological diagnosis relies on digital image quality, which, in turn, affects the rates of false positive and negative cellular objects designated as abnormalities. Cytogenetic biodosimetry is a genotoxic assay that detects dicentric chromosomes (DCs) arising from exposure to ionizing radiation. The frequency of DCs is related to radiation dose received, so the inferred radiation dose depends on the accuracy of DC detection. To improve this accuracy, image segmentation methods are used to rank high quality cytogenetic images and eliminate suboptimal metaphase cell data in a sample based on novel quality measures. When sufficient numbers of high quality images are found, the microscope system is directed to terminate metaphase image collection for a sample. The International Atomic Energy Agency recommends at least 500 images be used to estimate radiation dose, however often many more images are collected in order to select the metaphase cells with good morphology for analysis. Improvements in DC recognition increase the accuracy of dose estimates, by reducing false positive (FP) DC detection. A set of chromosome morphology segmentation methods selectively filtered out false DCs, arising primarily from extended prometaphase chromosomes, sister chromatid separation and chromosome fragmentation. This reduced FPs by 55% and was highly specific to the abnormal structures (≥97.7%). Additional procedures were then developed to fully automate image review, resulting in 6 image-level filters that, when combined, selectively remove images with consistently unparsable or incorrectly segmented chromosome morphologies. Overall, these filters can eliminate half of the FPs detected by manual image review. Optimal image selection and FP DCs are minimized by combining multiple feature based segmentation filters and a novel image sorting procedure based on the known distribution of chromosome lengths. Consequently, the average dose estimation error was reduced from 0.4 Gy to
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公开(公告)号：US11501545B2
公开(公告)日：2022-11-15
申请号：US17137317
申请日：2020-12-29
申请人： Peter Keith Rogan , Yanxin Li , Jin Liu
发明人： Peter Keith Rogan , Yanxin Li , Jin Liu
摘要： Automation of microscopic pathological diagnosis relies on digital image quality, which, in turn, affects the rates of false positive and negative cellular objects designated as abnormalities. Cytogenetic biodosimetry is a genotoxic assay that detects dicentric chromosomes (DCs) arising from exposure to ionizing radiation. The frequency of DCs is related to radiation dose received, so the inferred radiation dose depends on the accuracy of DC detection. To improve this accuracy, image segmentation methods are used to rank high quality cytogenetic images and eliminate suboptimal metaphase cell data in a sample based on novel quality measures. When sufficient numbers of high quality images are found, the microscope system is directed to terminate metaphase image collection for a sample. The International Atomic Energy Agency recommends at least 500 images be used to estimate radiation dose, however often many more images are collected in order to select the metaphase cells with good morphology for analysis. Improvements in DC recognition increase the accuracy of dose estimates, by reducing false positive (FP) DC detection. A set of chromosome morphology segmentation methods selectively filtered out false DCs, arising primarily from extended prometaphase chromosomes, sister chromatid separation and chromosome fragmentation. This reduced FPs by 55% and was highly specific to the abnormal structures (≥97.7%). Additional procedures were then developed to fully automate image review, resulting in 6 image-level filters that, when combined, selectively remove images with consistently unparsable or incorrectly segmented chromosome morphologies. Overall, these filters can eliminate half of the FPs detected by manual image review. Optimal image selection and FP DCs are minimized by combining multiple feature based segmentation filters and a novel image sorting procedure based on the known distribution of chromosome lengths. Consequently, the average dose estimation error was reduced from 0.4 Gy to
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公开(公告)号：US10929641B2
公开(公告)日：2021-02-23
申请号：US16057710
申请日：2018-08-07
申请人： Peter Keith Rogan , Yanxin Li , Jin Liu
发明人： Peter Keith Rogan , Yanxin Li , Jin Liu
摘要： An automated microscope system is described that detects dicentric chromosomes (DCs) in metaphase cells arising from exposure to ionizing radiation. The radiation dose depends on the accuracy of DC detection. Accuracy is increased using image segmentation methods are used to rank high quality cytogenetic images and eliminate suboptimal metaphase cell data in a sample based on novel quality measures. When a sufficient number of high quality images are detected, the microscope system is directed to terminate metaphase image collection for a sample. The microscope system integrates image selection procedures that control an automated digitally controlled microscope with the analysis of acquired metaphase cell images to accurately determine radiation dose. Early termination of image acquisition reduces sample processing time without compromising accuracy. This approach constitutes a reliable and scalable solution that will be essential for analysis of large numbers of potentially exposed individuals.
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公开(公告)号：US20200050831A1
公开(公告)日：2020-02-13
申请号：US16057710
申请日：2018-08-07
申请人： Peter Keith Rogan , Yanxin Li , Jin Liu
发明人： Peter Keith Rogan , Yanxin Li , Jin Liu
摘要： An automated microscope system is described that detects dicentric chromosomes (DCs) in metaphase cells arising from exposure to ionizing radiation. The radiation dose depends on the accuracy of DC detection. Accuracy is increased using image segmentation methods are used to rank high quality cytogenetic images and eliminate suboptimal metaphase cell data in a sample based on novel quality measures. When a sufficient number of high quality images are detected, the microscope system is directed to terminate metaphase image collection for a sample. The microscope system integrates image selection procedures that control an automated digitally controlled microscope with the analysis of acquired metaphase cell images to accurately determine radiation dose. Early termination of image acquisition reduces sample processing time without compromising accuracy. This approach constitutes a reliable and scalable solution that will be essential for analysis of large numbers of potentially exposed individuals.
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5.发明授权Centromere detector and method for determining radiation exposure from chromosome abnormalities 有权着丝粒检测器和确定染色体异常辐射暴露的方法公开(公告)号：US08605981B2
公开(公告)日：2013-12-10
申请号：US13822289
申请日：2011-11-04
IPC分类号： G06F19/16
CPC分类号： G06F19/16 , C12Q1/6883
摘要： A method for determining radiation exposure from chromosome abnormalities present in a specimen by determining the location or locations of the centromere of each chromosome in a cell in an image of a metaphase cell by segmentation of an accurately drawn chromosome centerline followed by selection of a longitudinal cross-section with the minimum width or intensity or width and intensity; counting the number of centromeres in each chromosome in each cell; computing the frequency of dicentric chromosomes in a population of cells; and determining the radiation dose by comparing the computed frequency of dicentric chromosomes with a previously determined dose-response curve from a calibrated source.
摘要翻译： 一种确定样品中存在的染色体异常的辐射暴露的方法，通过分割准确绘制的染色体中心线，然后选择纵向十字形来确定中期细胞图像中每个染色体的着丝粒的位置或位置 具有最小宽度或强度或宽度和强度的截面; 计算每个细胞每个染色体中着丝粒的数量; 计算细胞群中双染色体的频率; 并通过将计算出的双重染色体的频率与来自校准的源的预先确定的剂量 - 响应曲线进行比较来确定辐射剂量。
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6.发明申请METHODS OF PREDICTING AND DETERMINING MUTATED mRNA SPLICE ISOFORMS 审中-公开预测和确定MUTATED mRNA SPLICE ISOFORMS的方法公开(公告)号：US20140199698A1
公开(公告)日：2014-07-17
申请号：US14154905
申请日：2014-01-14
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6827 , G16B20/00 , G16B25/00 , C12Q2537/165 , C12Q2539/105
摘要： Mutations that affect mRNA splicing often produce multiple mRNA isoforms containing different exon structures. Definition of an exon and its inclusion in mature mRNA relies on joint recognition of both acceptor and donor splice sites. The instant methodology predicts cryptic and exon skipping isoforms in mRNA produced by splicing mutations from the combined information contents and the distribution of the splice sites and other regulatory binding sites defining these exons. In its simplest form, the total information content of an exon, Ri,total, is the sum of the information contents of its corresponding acceptor and donor splice sites, adjusted for the self-information of the exon length. Differences between Ri,total values of mutant versus normal exons are consistent with the relative abundance of these exons in distinct processed mRNAs. Predictions of splicing mutations based on Ri,total are highly concordant with published expression data demonstrating alterations in the structures and relative abundance of the mRNA transcripts derived from these mutations.
摘要翻译： 影响mRNA剪接的突变通常产生含有不同外显子结构的多种mRNA同种型。 外显子的定义及其在成熟mRNA中的含义依赖于受体和供体剪接位点的联合识别。 本方法预测了从组合的信息内容中剪接突变产生的mRNA产生的神经和外显子的异构体，以及剪接位点和定义这些外显子的其他调节结合位点的分布。 在其最简单的形式中，外显子的总信息内容Ri总计是根据外显子长度的自我信息进行调整的其对应受体和供体剪接位点的信息内容的总和。 Ri，突变体与正常外显子的总值之间的差异与不同加工的mRNA中这些外显子的相对丰度是一致的。 基于Ri，总共的剪接突变的预测与公开的表达数据高度一致，证明了从这些突变衍生的mRNA转录物的结构和相对丰度的变化。
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7.发明申请公开(公告)号：US20230075871A1
公开(公告)日：2023-03-09
申请号：US17402550
申请日：2021-08-15
IPC分类号： G16B20/00 , C12Q1/6883
摘要： The present invention discloses a method for determining improved radiation gene expression profiles by sequential application of sensitive and specific gene signatures. The method involves evaluating a sample of target cells from a patient against a highly sensitive, first radiation gene signature, to determine the radiation exposed gene signature. If the signature does not completely distinguish radiation exposures from other conditions or phenotypes, the sample may be evaluated against a second radiation gene signature, which is a radiation gene signature with high specificity. On sequential application of sensitive and specific gene signatures, any misclassified unirradiated samples remaining in the determined gene signatures are identified and removed. Thus, the method enables rejection of radiation signatures with high false positive radiation diagnosis in conditions that confound the results with the first signature. The method derives individual or sequential sensitive and specific radiation signatures with low misclassification rates due to confounding phenotypes, in either controls and test samples.
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公开(公告)号：US20210057109A1
公开(公告)日：2021-02-25
申请号：US16996792
申请日：2020-08-18
摘要： The present invention discloses a method for identifying and quantifying populations exposed to environmental hazards across a geographic region. The environmental hazards include radiation, pollution and communicable infectious agent hotspots, such as locations of COVID-19 hotspots. The method of the present invention uses geographic distributions of infected individuals over time to develop robust methods that pinpoint locations of emerging COVID-19 hotspots. The method assays a fraction of infected individuals of a local population and adjacent locations of the infected individuals and detects spatial asymmetries and clustered distributions of infected individuals. The spatial resolution of the assay is increased by assigning infected cases in each county to subdivisions weighted by population census and performing spatial interpolation to pinpoint potential local clusters of infected individuals.
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公开(公告)号：US09624549B2
公开(公告)日：2017-04-18
申请号：US13744459
申请日：2013-01-18
CPC分类号： C12Q1/6886 , C12Q2600/106 , C12Q2600/156 , C12Q2600/158
摘要： A method for determining genes in breast cancer that are stable in copy number, expression and sequence in tumors from nearly all patients. Certain stable genes are targets of standard chemotherapy. The effectiveness of therapies that act upon these targets depends on maintaining the stability and integrity of these genes in tumors. Mutations in these targets result in poor response to therapies that target these gene products. In the instant invention, ordinarily stable gene targets are characterized as either normal or mutant for the purpose of determining whether to include or exclude particular drugs as potential treatments.
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10.发明申请STABLE GENE TARGETS IN BREAST CANCER AND USE THEREOF FOR OPTIMIZING THERAPY 审中-公开乳腺癌中稳定的基因靶点及其用于优化治疗公开(公告)号：US20140206543A1
公开(公告)日：2014-07-24
申请号：US13744459
申请日：2013-01-18
IPC分类号： G06F19/18
CPC分类号： C12Q1/6886 , C12Q2600/106 , C12Q2600/156 , C12Q2600/158
摘要： A method for determining genes in breast cancer that are stable in copy number, expression and sequence in tumors from nearly all patients. Certain stable genes are targets of standard chemotherapy. The effectiveness of therapies that act upon these targets depends on maintaining the stability and integrity of these genes in tumors. Mutations in these targets result in poor response to therapies that target these gene products. In the instant invention, ordinarily stable gene targets are characterized as either normal or mutant for the purpose of determining whether to include or exclude particular drugs as potential treatments.
摘要翻译： 确定几乎所有患者肿瘤中拷贝数，表达和序列稳定的乳腺癌基因的方法。 某些稳定基因是标准化疗的靶标。 作用于这些靶标的疗法的有效性取决于维持这些基因在肿瘤中的稳定性和完整性。 这些目标的突变导致针对这些基因产物的疗法的反应差。 在本发明中，为了确定是否包括或排除特定药物作为潜在的治疗，通常将稳定的基因靶标表征为正常或突变体。
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