公开(公告)号：WO2015061359A1

公开(公告)日：2015-04-30

申请号：PCT/US2014/061635

申请日：2014-10-21

申请人： VERINATA HEALTH, INC.

发明人： CHUDOVA, Darya I. ,  ABDUEVA, Diana ,  RAVA, Richard P.

IPC分类号： G06F19/20 ,  G06F19/22

CPC分类号： G06F19/20 ,  G06F19/00 ,  G16H50/20

摘要： Disclosed are methods for determining copy number variation (CNV) known or suspected to be associated with a variety of medical conditions. In some embodiments, methods are provided for determining copy number variation (CNV) of fetuses using maternal samples comprising maternal and fetal cell free DNA. In some embodiments, methods are provided for determining CNVs known or suspected to be associated with a variety of medical conditions. Some embodiments disclosed herein provide methods to improve the sensitivity and/or specificity of sequence data analysis by removing within-sample GC-content bias. In some embodiments, removal of within-sample GC-content bias is based on sequence data corrected for systematic variation common across unaffected training samples. Also disclosed are systems and computer program products for evaluation of CNV of sequences of interest.

摘要翻译： 公开了用于确定已知或怀疑与各种医学状况相关联的拷贝数变异（CNV）的方法。 在一些实施方案中，提供了使用包含母体和胎儿无细胞DNA的母体样品来确定胎儿的拷贝数变异（CNV）的方法。 在一些实施例中，提供了用于确定已知或怀疑与各种医疗状况相关联的CNV的方法。 本文公开的一些实施方案提供通过移除样品内含量偏差来提高序列数据分析的灵敏度和/或特异性的方法。 在一些实施方案中，样本内GC含量偏差的去除是基于校正的针对未受影响的训练样本共同的系统变化的序列数据。 还公开了用于评估感兴趣序列的CNV的系统和计算机程序产品。

公开(公告)号：WO2014204991A1

公开(公告)日：2014-12-24

申请号：PCT/US2014/042785

申请日：2014-06-17

申请人： VERINATA HEALTH, INC.

发明人： ABDUEVA, Diana

IPC分类号： C12Q1/68 ,  G06F19/24

CPC分类号： G06F19/22 ,  C12Q1/6827 ,  G06F19/18 ,  C12Q2537/16 ,  C12Q2537/165

摘要： The invention provides methods for determining copy number of the Y chromosome, including, but not limited to, methods for gender determination or Y chromosome aneuploidy of fetus using maternal samples comprising maternal and fetal cell free DNA. Some embodiments disclosed herein describe a strategy for filtering out (or masking) non-discriminant sequence reads on chromosome Y using representative training set of female samples. In some embodiments, this filtering strategy is also applicable to filtering autosomes for evaluation of copy number variation of sequences on the autosomes. In some embodiments, methods are provided for determining copy number variation (CNV) of any fetal aneuploidy, and CNVs known or suspected to be associated with a variety of medical conditions. Also disclosed are systems for evaluation of CNV of sequences of interest on the Y chromosome and other chromosomes.

摘要翻译： 本发明提供用于确定Y染色体的拷贝数的方法，包括但不限于使用包含母体和胎儿无细胞DNA的母体样品进行性别测定或胎儿Y染色体非整倍性的方法。 本文公开的一些实施例描述了使用女性样本的代表训练集来过滤（或掩蔽）染色体Y上的非判别序列读取的策略。 在一些实施方案中，该过滤策略也适用于过滤用于评估常染色体上序列的拷贝数变异的常数。 在一些实施方案中，提供了用于确定任何胎儿非整倍性的拷贝数变异（CNV）和已知或怀疑与各种医学状况相关联的CNV的方法。 还公开了用于评估Y染色体和其他染色体上感兴趣序列的CNV的系统。

公开(公告)号：WO2015184404A1

公开(公告)日：2015-12-03

申请号：PCT/US2015/033403

申请日：2015-05-29

申请人： VERINATA HEALTH, INC.

发明人： CHUDOVA, Darya I. ,  ABDUEVA, Diana

IPC分类号： C12Q1/68 ,  G06F19/20

CPC分类号： G06F19/22 ,  C12Q1/6858 ,  C12Q1/6869 ,  G06F19/18 ,  C12Q2535/122 ,  C12Q2537/16 ,  C12Q2537/165

摘要： Disclosed are methods for determining copy number variation (CNV) known or suspected to be associated with a variety of medical conditions, including syndromes related to CNV of subchromosomal regions wherein the bins from the unaffected training samples used as controls have a coverage similar to the coverage of the region inspected for CNV. In some embodiments, methods are provided for determining CNV of fetuses using maternal samples comprising maternal and fetal cell free DNA. Some embodiments disclosed herein provide methods to improve the sensitivity and/or specificity of sequence data analysis by removing within-sample GC-content bias. In some embodiments, removal of within-sample GC-content bias is based on sequence data corrected for systematic variation common across unaffected training samples. In some embodiments, syndrome related biases in sample data are also removed to increase signal to noise ratio. Also disclosed are systems for evaluation of CNV of sequences of interest.

摘要翻译： 公开了用于确定已知或怀疑与各种医学状况相关的拷贝数变异（CNV）的方法，包括与亚染色体区域的CNV相关的综合征，其中来自用于对照的未受影响的训练样本的箱具有与覆盖类似的覆盖 的区域检查CNV。 在一些实施方案中，提供了使用包含母体和胎儿无细胞DNA的母体样品来确定胎儿CNV的方法。 本文公开的一些实施方案提供了通过去除样品内含量偏差来提高序列数据分析的灵敏度和/或特异性的方法。 在一些实施方案中，样本内GC含量偏差的去除是基于针对未受影响的训练样本共同的系统变化而校正的序列数据。 在一些实施例中，样本数据中的相关偏差也被去除以增加信噪比。 还公开了用于评价感兴趣序列的CNV的系统。