CN111370129A - 甲状腺肿瘤良恶性鉴别模型及其应用 - Google Patents
甲状腺肿瘤良恶性鉴别模型及其应用 Download PDFInfo
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Abstract
Description
准确性 | 灵敏性 | 特异性 | AUC | |
RF | 0.9615385 | 0.9230769 | 1 | 0.9940828 |
SVM | 0.6538462 | 1 | 0.3076923 | 0.9349112 |
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Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN113186278A (zh) * | 2021-07-01 | 2021-07-30 | 上海鹍远生物技术有限公司 | 甲状腺结节良恶性相关标志物及其应用 |
CN113295815A (zh) * | 2021-05-24 | 2021-08-24 | 南京鼓楼医院 | 子宫内膜分泌期不同时间点的标志分子及其筛选方法 |
CN114277115A (zh) * | 2020-09-27 | 2022-04-05 | 上海鹍远生物科技股份有限公司 | 甲状腺结节良恶性相关标志物及其应用 |
CN115274124A (zh) * | 2022-07-22 | 2022-11-01 | 江苏先声医学诊断有限公司 | 一种基于数据驱动的肿瘤早筛靶向Panel和分类模型的动态优化方法 |
WO2023274350A1 (zh) * | 2021-07-01 | 2023-01-05 | 上海鹍远生物科技股份有限公司 | 甲状腺结节良恶性相关标志物及其应用 |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20160340740A1 (en) * | 2014-01-30 | 2016-11-24 | The Regents Of The University Of California | Methylation haplotyping for non-invasive diagnosis (monod) |
CN109680060A (zh) * | 2017-10-17 | 2019-04-26 | 华东师范大学 | 甲基化标志物及其在肿瘤诊断、分类中的应用 |
CN110431241A (zh) * | 2017-02-28 | 2019-11-08 | 梅约医学教育与研究基金会 | 检测前列腺癌 |
CN110438228A (zh) * | 2019-07-31 | 2019-11-12 | 南通大学附属医院 | 结直肠癌dna甲基化标志物 |
CN110982907A (zh) * | 2020-02-27 | 2020-04-10 | 上海鹍远生物技术有限公司 | 甲状腺结节相关rDNA甲基化标志物及其应用 |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20200109456A1 (en) * | 2017-05-12 | 2020-04-09 | President And Fellows Of Harvard College | Universal early cancer diagnostics |
CN110283907A (zh) * | 2019-05-31 | 2019-09-27 | 江苏大学 | 甲状腺恶性肿瘤的特异性基因标志物及其应用 |
-
2020
- 2020-04-20 CN CN202010313087.3A patent/CN111370129B/zh active Active
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Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20160340740A1 (en) * | 2014-01-30 | 2016-11-24 | The Regents Of The University Of California | Methylation haplotyping for non-invasive diagnosis (monod) |
CN106232833A (zh) * | 2014-01-30 | 2016-12-14 | 加利福尼亚大学董事会 | 用于非侵入性诊断的甲基化单体型分析(monod) |
CN110431241A (zh) * | 2017-02-28 | 2019-11-08 | 梅约医学教育与研究基金会 | 检测前列腺癌 |
CN109680060A (zh) * | 2017-10-17 | 2019-04-26 | 华东师范大学 | 甲基化标志物及其在肿瘤诊断、分类中的应用 |
CN110438228A (zh) * | 2019-07-31 | 2019-11-12 | 南通大学附属医院 | 结直肠癌dna甲基化标志物 |
CN110982907A (zh) * | 2020-02-27 | 2020-04-10 | 上海鹍远生物技术有限公司 | 甲状腺结节相关rDNA甲基化标志物及其应用 |
Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN114277115A (zh) * | 2020-09-27 | 2022-04-05 | 上海鹍远生物科技股份有限公司 | 甲状腺结节良恶性相关标志物及其应用 |
CN113295815A (zh) * | 2021-05-24 | 2021-08-24 | 南京鼓楼医院 | 子宫内膜分泌期不同时间点的标志分子及其筛选方法 |
CN113186278A (zh) * | 2021-07-01 | 2021-07-30 | 上海鹍远生物技术有限公司 | 甲状腺结节良恶性相关标志物及其应用 |
CN113186278B (zh) * | 2021-07-01 | 2021-10-12 | 上海鹍远生物技术有限公司 | 甲状腺结节良恶性相关标志物及其应用 |
WO2023274350A1 (zh) * | 2021-07-01 | 2023-01-05 | 上海鹍远生物科技股份有限公司 | 甲状腺结节良恶性相关标志物及其应用 |
CN115274124A (zh) * | 2022-07-22 | 2022-11-01 | 江苏先声医学诊断有限公司 | 一种基于数据驱动的肿瘤早筛靶向Panel和分类模型的动态优化方法 |
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