CA2915626A1 - Method for determining copy number variations in sex chromosomes - Google Patents
Method for determining copy number variations in sex chromosomes Download PDFInfo
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- CA2915626A1 CA2915626A1 CA2915626A CA2915626A CA2915626A1 CA 2915626 A1 CA2915626 A1 CA 2915626A1 CA 2915626 A CA2915626 A CA 2915626A CA 2915626 A CA2915626 A CA 2915626A CA 2915626 A1 CA2915626 A1 CA 2915626A1
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| CN106845154B (zh) * | 2016-12-29 | 2022-04-08 | 浙江安诺优达生物科技有限公司 | 一种用于ffpe样本拷贝数变异检测的装置 |
| US11342047B2 (en) | 2017-04-21 | 2022-05-24 | Illumina, Inc. | Using cell-free DNA fragment size to detect tumor-associated variant |
| CN107119145A (zh) * | 2017-07-13 | 2017-09-01 | 深圳瑞科生物科技有限公司 | 一种基于ddPCR定量检测ctDNA的方法 |
| CN109390039B (zh) * | 2017-08-11 | 2020-10-16 | 深圳华大基因股份有限公司 | 一种统计dna拷贝数信息的方法、装置及存储介质 |
| CN111052249B (zh) * | 2017-09-15 | 2024-04-05 | 深圳华大智造科技股份有限公司 | 确定预定染色体保守区域的方法、确定样本基因组中是否存在拷贝数变异的方法、系统和计算机可读介质 |
| US11168356B2 (en) * | 2017-11-02 | 2021-11-09 | The Chinese University Of Hong Kong | Using nucleic acid size range for noninvasive cancer detection |
| CN110800061B (zh) | 2017-11-16 | 2024-10-11 | 伊鲁米那股份有限公司 | 用于确定微卫星不稳定性的系统和方法 |
| CN108427864B (zh) * | 2018-02-14 | 2019-01-29 | 南京世和基因生物技术有限公司 | 一种拷贝数变异的检测方法、装置以及计算机可读介质 |
| US12154661B2 (en) | 2018-03-22 | 2024-11-26 | The Regents Of The University Of Michigan | Method and apparatus for analysis of chromatin interaction data |
| TW202410055A (zh) * | 2018-06-01 | 2024-03-01 | 美商格瑞爾有限責任公司 | 用於資料分類之卷積神經網路系統及方法 |
| CN109136371B (zh) * | 2018-07-25 | 2019-11-01 | 南京世和基因生物技术有限公司 | 一种放疗疗效和毒性反应相关基因组合、检测探针库以及检测试剂盒 |
| KR102405245B1 (ko) * | 2018-07-27 | 2022-06-07 | 주식회사 지씨지놈 | 전장유전체 시퀀싱 기반의 염색체 이상 검출 방법 및 그 용도 |
| US11581062B2 (en) | 2018-12-10 | 2023-02-14 | Grail, Llc | Systems and methods for classifying patients with respect to multiple cancer classes |
| CN113795887A (zh) * | 2019-03-10 | 2021-12-14 | 阿尔缇玛基因组学公司 | 用于序列判定的方法和系统 |
| CN111755066B (zh) * | 2019-03-27 | 2022-10-18 | 欧蒙医学诊断（中国）有限公司 | 一种拷贝数变异的检测方法和实施该方法的设备 |
| CN110534202A (zh) * | 2019-08-21 | 2019-12-03 | 江南大学附属医院（无锡市第四人民医院） | 一种针对Sox10在三阴性乳腺癌中的表达进行分析的系统 |
| IL298458A (en) | 2020-05-22 | 2023-01-01 | Aqtual Inc | Methods for characterizing cell-free nucleic acid fragments |
| CN113409885B (zh) * | 2021-06-21 | 2022-09-20 | 天津金域医学检验实验室有限公司 | 一种自动化数据处理以及作图方法及系统 |
| CN114420208B (zh) * | 2022-02-28 | 2023-04-18 | 上海亿康医学检验所有限公司 | 一种用于鉴定核酸样本中cnv的方法和装置 |
| JP7331325B1 (ja) | 2022-08-30 | 2023-08-23 | 株式会社seeDNA | ２種以上の検査を実施可能な遺伝学的解析方法 |
| CN115273984B (zh) * | 2022-09-30 | 2022-11-29 | 北京诺禾致源科技股份有限公司 | 鉴定基因组串联重复区域的方法及装置 |
| CN115394359B (zh) * | 2022-10-27 | 2023-03-24 | 北京大学第三医院（北京大学第三临床医学院） | 一种通过转录组检测单细胞染色体拷贝数变异方法 |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7235358B2 (en) * | 2001-06-08 | 2007-06-26 | Expression Diagnostics, Inc. | Methods and compositions for diagnosing and monitoring transplant rejection |
| CA2668818C (en) | 2006-10-10 | 2018-06-26 | Xenomics, Inc. | Compositions, methods and kits for isolating nucleic acids from body fluids using anion exchange media |
| US8262900B2 (en) | 2006-12-14 | 2012-09-11 | Life Technologies Corporation | Methods and apparatus for measuring analytes using large scale FET arrays |
| CN101889074A (zh) | 2007-10-04 | 2010-11-17 | 哈尔西恩莫尔丘勒公司 | 采用电子显微镜对核酸聚合物测序 |
| GB0811500D0 (en) * | 2008-06-20 | 2008-07-30 | Univ Cardiff | Method of determining DNA copy number |
| WO2011050341A1 (en) * | 2009-10-22 | 2011-04-28 | National Center For Genome Resources | Methods and systems for medical sequencing analysis |
| WO2011090556A1 (en) | 2010-01-19 | 2011-07-28 | Verinata Health, Inc. | Methods for determining fraction of fetal nucleic acid in maternal samples |
| EP3006573B1 (en) | 2010-01-19 | 2018-03-07 | Verinata Health, Inc | Methods for determining fraction of fetal nucleic acids in maternal samples |
| US9260745B2 (en) | 2010-01-19 | 2016-02-16 | Verinata Health, Inc. | Detecting and classifying copy number variation |
| US20120046877A1 (en) * | 2010-07-06 | 2012-02-23 | Life Technologies Corporation | Systems and methods to detect copy number variation |
| US20120034603A1 (en) * | 2010-08-06 | 2012-02-09 | Tandem Diagnostics, Inc. | Ligation-based detection of genetic variants |
| JP6153874B2 (ja) * | 2011-02-09 | 2017-06-28 | ナテラ， インコーポレイテッド | 非侵襲的出生前倍数性呼び出しのための方法 |
| CN103003447B (zh) * | 2011-07-26 | 2020-08-25 | 维里纳塔健康公司 | 用于确定样品中存在或不存在不同非整倍性的方法 |
| US8688388B2 (en) * | 2011-10-11 | 2014-04-01 | Sequenom, Inc. | Methods and processes for non-invasive assessment of genetic variations |
| US9538439B2 (en) * | 2013-05-10 | 2017-01-03 | Qualcomm Incorporated | Method and apparatus for estimating an achievable link throughput based on assistance information |
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