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1. 发明授权

US09679103B2 Phasing of heterozygous loci to determine genomic haplotypes 有权
公开(公告)号：US09679103B2
公开(公告)日：2017-06-13
申请号：US13591723
申请日：2012-08-22
申请人： Bahram Ghaffarzadeh Kermani , Radoje Drmanac
发明人： Bahram Ghaffarzadeh Kermani , Radoje Drmanac
IPC分类号： G01N33/50 , G06F19/18 , G06F19/22
CPC分类号： G06F19/18 , G06F19/22
摘要： Haplotypes of one or more portions of a chromosome of an organism from sequencing information of DNA or RNA fragments can be determined. Heterozygous loci (hets) can be used to determine haplotypes. One allele on a first het can be connected (likely to be on the same haplotype) to an allele on a second het, thereby defining a particular orientation between the hets. Haplotypes can be assembled through these connections. Errors can be identified through redundant connection information, particularly using a confidence value (strength) for a particular connection. The connections among a set of hets can be analyzed to determine likely haplotypes for that set, e.g., an optimal tree of a graph containing the hets. Furthermore, haplotypes of different contiguous sections (contig) of the chromosome can be matched to a particular chromosome copy (e.g., to a particular parental copy). Thus, the phase of an entire chromosome can be determined.

2. 发明申请

US20150379192A9 Processing and Analysis of Complex Nucleic Acid Sequence Data 有权
标题翻译：复杂核酸序列数据的处理与分析
公开(公告)号：US20150379192A9
公开(公告)日：2015-12-31
申请号：US13447087
申请日：2012-04-13
申请人： Radoje Drmanac , Brock A. Peters , Bahram Ghaffarzadeh Kermani
发明人： Radoje Drmanac , Brock A. Peters , Bahram Ghaffarzadeh Kermani
IPC分类号： G06F19/22
CPC分类号： G06F19/22 , C12Q1/6869 , C12Q2537/159 , C12Q2549/10
摘要： The present invention is directed to logic for analysis of nucleic acid sequence data that employs algorithms that lead to a substantial improvement in sequence accuracy and that can be used to phase sequence variations, e.g., in connection with the use of the long fragment read (LFR) process.
摘要翻译：本发明涉及用于分析核酸序列数据的逻辑，其使用导致序列精度的实质性改进并且可用于相序变化的算法，例如结合使用长片段读取（LFR ）过程。

3. 发明授权

US08951731B2 Sequence analysis using decorated nucleic acids 有权
标题翻译：使用装饰核酸的序列分析
公开(公告)号：US08951731B2
公开(公告)日：2015-02-10
申请号：US12252280
申请日：2008-10-15
申请人： Radoje Drmanac , Snezana Drmanac
发明人： Radoje Drmanac , Snezana Drmanac
IPC分类号： C12Q1/68 , C12P19/34
CPC分类号： C12Q1/6869 , C12Q1/6825 , C12Q1/6874 , C12Q2565/631 , C12Q2535/119 , C12Q2521/319
摘要： The present invention provides a sequence interrogation chemistry that combines the accuracy and haplotype integrity of long-read sequencing with improved methods of preparing genomic nucleic acids and analyzing sequence information generated from those nucleic acids. The present invention encompasses compositions comprising decorated nucleic acids stretched on substrates. The present invention further encompasses methods of making stretched decorated nucleic acids and methods of using decorated nucleic acids to obtain sequence information.
摘要翻译：本发明提供了序列询问化学，其将长读取测序的准确度和单倍型完整性与改进的制备基因组核酸的方法和分析从这些核酸产生的序列信息相结合。本发明包括包含在底物上拉伸的装饰的核酸的组合物。本发明还包括制备延伸的装饰的核酸的方法和使用装饰的核酸获得序列信息的方法。

4. 发明授权

US08609335B2 Self-assembled single molecule arrays and uses thereof 有权
标题翻译：自组装单分子阵列及其用途
公开(公告)号：US08609335B2
公开(公告)日：2013-12-17
申请号：US13098965
申请日：2011-05-02
申请人： Radoje Drmanac , Matthew J. Callow , Brian K. Hauser , George Yeung
发明人： Radoje Drmanac , Matthew J. Callow , Brian K. Hauser , George Yeung
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6837 , C12N15/1093 , C12Q1/682 , C12Q1/6869 , C12Q1/6874 , C12Q2531/125 , C12Q2525/313 , C12Q2525/151 , C12Q2521/313 , C12Q2565/513 , C12Q2521/307
摘要： The present invention provides methods of making and using self-assembled arrays of single polynucleotide molecules for carrying out a variety of large-scale genetic measurements, such as gene expression analysis, gene copy number assessment, and the like. Random arrays used in the invention are “self-assembled” in the sense that they are formed by deposition of polynucleotide molecules onto a surface where they become fixed at random locations. The polynucleotide molecules fixed on the surface are then identified by direct sequence determination of component nucleic acids, such as incorporated probe sequences, or by other decoding schemes. Such identification converts a random array of determinable polynucleotides, and their respective probes into an addressable array of probe sequences.
摘要翻译：本发明提供制造和使用单个多核苷酸分子的自组装阵列进行各种大规模遗传测量的方法，例如基因表达分析，基因拷贝数评估等。在本发明中使用的随机阵列是“自组装”的意思，即它们通过将多核苷酸分子沉积到其随机位置固定的表面上而形成。然后通过直接序列测定组分核酸，例如并入的探针序列或其他解码方案来鉴定固定在表面上的多核苷酸分子。这种鉴定将随机阵列的可测定多核苷酸及其各自的探针转换成可寻址的探针序列阵列。

5. 发明授权

US08445194B2 Single molecule arrays for genetic and chemical analysis 有权
公开(公告)号：US08445194B2
公开(公告)日：2013-05-21
申请号：US11451691
申请日：2006-06-13
申请人： Radoje Drmanac , Matthew J. Callow , Snezana Drmanac , Brian K. Hauser , George Yeung
发明人： Radoje Drmanac , Matthew J. Callow , Snezana Drmanac , Brian K. Hauser , George Yeung
IPC分类号： C12Q1/68 , C12M1/36 , C07H21/04
CPC分类号： C12Q1/6874 , C07H21/04 , C07K1/047 , C12Q1/6806 , C12Q1/682 , C12Q1/6837 , C12Q1/6869 , C12Q2525/151 , C12Q2525/313 , C12Q2531/125 , C12Q2565/513 , G01N15/1404 , G01N15/1434 , Y10S977/778 , Y10S977/789 , Y10S977/792 , Y10S977/88 , Y10S977/882 , C12Q2521/307 , C12Q2525/161 , C12Q2535/122 , C12Q2563/179 , C12Q2565/514
摘要： Random arrays of single molecules are provided for carrying out large scale analyses, particularly of biomolecules, such as genomic DNA, cDNAs, proteins, and the like. In one aspect, arrays of the invention comprise concatemers of DNA fragments that are randomly disposed on a regular array of discrete spaced apart regions, such that substantially all such regions contain no more than a single concatemer. Preferably, such regions have areas substantially less than 1 μm2 and have nearest neighbor distances that permit optical resolution of on the order of 109 single molecules per cm2. Many analytical chemistries can be applied to random arrays of the invention, including sequencing by hybridization chemistries, sequencing by synthesis chemistries, SNP detection chemistries, and the like, to greatly expand the scale and potential applications of such techniques.

6. 发明申请

US20130054151A1 PHASING OF HETEROZYGOUS LOCI TO DETERMINE GENOMIC HAPLOTYPES 有权
标题翻译：异位定位法测定基因组HAPLOTYPES
公开(公告)号：US20130054151A1
公开(公告)日：2013-02-28
申请号：US13591723
申请日：2012-08-22
申请人： Bahram Ghaffarzadeh Kermani , Radoje Drmanac
发明人： Bahram Ghaffarzadeh Kermani , Radoje Drmanac
IPC分类号： G06F19/18
CPC分类号： G06F19/18 , G06F19/22
摘要： Haplotypes of one or more portions of a chromosome of an organism from sequencing information of DNA or RNA fragments can be determined. Heterozygous loci (hets) can be used to determine haplotypes. One allele on a first het can be connected (likely to be on the same haplotype) to an allele on a second het, thereby defining a particular orientation between the hets. Haplotypes can be assembled through these connections. Errors can be identified through redundant connection information, particularly using a confidence value (strength) for a particular connection. The connections among a set of hets can be analyzed to determine likely haplotypes for that set, e.g., an optimal tree of a graph containing the hets. Furthermore, haplotypes of different contiguous sections (contig) of the chromosome can be matched to a particular chromosome copy (e.g., to a particular parental copy). Thus, the phase of an entire chromosome can be determined.
摘要翻译：可以测定生物体的染色体的一个或多个部分的单倍型，从DNA或RNA片段的测序信息。杂合基因座（hets）可用于确定单元型。第一次的一个等位基因可以连接（可能在相同的单倍型上）到第二个等位基因上，从而在ert之间定义一个特定的取向。单体可以通过这些连接组装。可以通过冗余连接信息识别错误，特别是使用特定连接的置信度值（强度）。可以分析一组ts之间的连接以确定该集合的可能单倍型，例如包含he a的图的最佳树。此外，染色体的不同连续切片（contig）的单元型可以与特定染色体拷贝（例如，特定的亲本拷贝）匹配。因此，可以确定整个染色体的相位。

7. 发明授权

US08298768B2 Efficient shotgun sequencing methods 有权
标题翻译：高效霰弹枪测序方法
公开(公告)号：US08298768B2
公开(公告)日：2012-10-30
申请号：US12325922
申请日：2008-12-01
申请人： Radoje Drmanac , Clifford Reid
发明人： Radoje Drmanac , Clifford Reid
IPC分类号： C12Q1/68 , C12P19/34
CPC分类号： C12Q1/6869 , C12Q1/6874 , C12Q2549/119 , C12Q2537/149 , C12Q2565/137
摘要： Methods are provided for efficient shotgun sequencing to allow efficient selection and sequencing of nucleic acids of interest contained in a library. The nucleic acids of interest can be defined any time before or after preparation of the library. One example of nucleic acids of interest is missing or low confidence genome sequences resulting from an initial sequencing procedure. Other nucleic acids of interest include subsets of genomic DNA, RNA or cDNAs (exons, genes, gene sets, transciptomes). By designing an efficient (simple to implement, speedy, high specificity, low cost) selection procedure, a more complete sequence is achieved with less effort than by using highly redundant shotgun sequencing in an initial sequencing procedure.
摘要翻译：提供了有效的霰弹枪测序的方法，以允许文库中包含的感兴趣的核酸的有效选择和测序。感兴趣的核酸可以在文库制备之前或之后的任何时间进行定义。感兴趣的核酸的一个实例是由初始测序程序产生的缺失或低置信基因组序列。感兴趣的其他核酸包括基因组DNA，RNA或cDNAs（外显子，基因，基因组，转录本）的子集。通过设计一种高效（简单易于实施，快速，高特异性，低成本）选择程序，通过在初始测序程序中使用高度冗余的霰弹枪测序，以更少的努力实现更完整的顺序。

8. 发明授权

US08133719B2 Methods for making single molecule arrays 有权
标题翻译：制备单分子阵列的方法
公开(公告)号：US08133719B2
公开(公告)日：2012-03-13
申请号：US11981607
申请日：2007-10-31
申请人： Radoje Drmanac , Matthew J. Callow , Snezana Drmanac , Brian K. Hauser , George Yeung
发明人： Radoje Drmanac , Matthew J. Callow , Snezana Drmanac , Brian K. Hauser , George Yeung
IPC分类号： C12M1/36 , C07H21/04 , C12P19/34
CPC分类号： C12Q1/6874 , C07H21/04 , C07K1/047 , C12Q1/6806 , C12Q1/682 , C12Q1/6837 , C12Q1/6869 , C12Q2525/151 , C12Q2525/313 , C12Q2531/125 , C12Q2565/513 , G01N15/1404 , G01N15/1434 , Y10S977/778 , Y10S977/789 , Y10S977/792 , Y10S977/88 , Y10S977/882 , C12Q2521/307 , C12Q2525/161 , C12Q2535/122 , C12Q2563/179 , C12Q2565/514
摘要： Random arrays of single molecules are provided for carrying out large scale analyses, particularly of biomolecules, such as genomic DNA, cDNAs, proteins, and the like. In one aspect, arrays of the invention comprise concatemers of DNA fragments that are randomly disposed on a regular array of discrete spaced apart regions, such that substantially all such regions contain no more than a single concatemer. Preferably, such regions have areas substantially less than 1 μm2 and have nearest neighbor distances that permit optical resolution of on the order of 109 single molecules per cm2. Many analytical chemistries can be applied to random arrays of the invention, including sequencing by hybridization chemistries, sequencing by synthesis chemistries, SNP detection chemistries, and the like, to greatly expand the scale and potential applications of such techniques.
摘要翻译：提供单个分子的随机阵列用于进行大规模分析，特别是生物分子，例如基因组DNA，cDNAs，蛋白质等。在一个方面，本发明的阵列包括随机设置在离散间隔开的区域的规则阵列上的DNA片段的并列物质，使得基本上所有这些区域都包含不超过单个并联体。优选地，这样的区域具有基本上小于1μm2的面积，并且具有最近的相邻距离，其允许每厘米每分钟109个单分子的光学分辨率。许多分析化学物质可以应用于本发明的随机阵列，包括杂交化学测序，合成化学测序，SNP检测化学等，以大大扩展这些技术的规模和潜在应用。

9. 发明申请

US20100081128A1 Self-assembled single molecule arrays and uses thereof 有权
标题翻译：自组装单分子阵列及其用途
公开(公告)号：US20100081128A1
公开(公告)日：2010-04-01
申请号：US11541225
申请日：2006-09-29
申请人： Radoje Drmanac , Matthew J. Callow , Brian K. Hauser , George Yeung
发明人： Radoje Drmanac , Matthew J. Callow , Brian K. Hauser , George Yeung
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6837 , C12N15/1093 , C12Q1/682 , C12Q1/6869 , C12Q1/6874 , C12Q2531/125 , C12Q2525/313 , C12Q2525/151 , C12Q2521/313 , C12Q2565/513 , C12Q2521/307
摘要： The present invention provides methods of making and using self-assembled arrays of single polynucleotide molecules for carrying out a variety of large-scale genetic measurements, such as gene expression analysis, gene copy number assessment, and the like. Random arrays used in the invention are “self-assembled” in the sense that they are formed by deposition of polynucleotide molecules onto a surface where they become fixed at random locations. The polynucleotide molecules fixed on the surface are then identified by direct sequence determination of component nucleic acids, such as incorporated probe sequences, or by other decoding schemes. Such identification converts a random array of determinable polynucleotides, and their respective probes into an addressable array of probe sequences.
摘要翻译：本发明提供制造和使用单个多核苷酸分子的自组装阵列进行各种大规模遗传测量的方法，例如基因表达分析，基因拷贝数评估等。在本发明中使用的随机阵列是“自组装”的意思，即它们通过将多核苷酸分子沉积到其随机位置固定的表面上而形成。然后通过直接序列测定组分核酸，例如并入的探针序列或其他解码方案来鉴定固定在表面上的多核苷酸分子。这种鉴定将随机阵列的可测定多核苷酸及其各自的探针转换成可寻址的探针序列阵列。

10. 发明申请

US20090264299A1 High throughput genome sequencing on DNA arrays 审中-公开
公开(公告)号：US20090264299A1
公开(公告)日：2009-10-22
申请号：US11679124
申请日：2007-02-26
申请人： Radoje Drmanac , Matthew J. Callow , Snezana Drmanac
发明人： Radoje Drmanac , Matthew J. Callow , Snezana Drmanac
IPC分类号： C40B20/02 , C40B20/00 , C40B50/06 , C40B40/06
CPC分类号： C12Q1/6874 , C12N15/64 , C12N15/66 , Y10T436/143333 , C12Q2521/313 , C12Q2525/191 , C12Q2525/151 , C12Q2525/131 , C12Q2565/518 , C12Q2533/107 , C12Q2531/125
摘要： The present invention is directed to methods and compositions for acquiring nucleotide sequence information of target sequences using adaptors interspersed in target polynucleotides. The sequence information can be new, e.g. sequencing unknown nucleic acids, re-sequencing, or genotyping. The invention preferably includes methods for inserting a plurality of adaptors at spaced locations within a target polynucleotide or a fragment of a polynucleotide. Such adaptors may serve as platforms for interrogating adjacent sequences using various sequencing chemistries, such as those that identify nucleotides by primer extension, probe ligation, and the like. Encompassed in the invention are methods and compositions for the insertion of known adaptor sequences into target sequences, such that there is an interruption of contiguous target sequence with the adaptors. By sequencing both “upstream” and “downstream” of the adaptors, identification of entire target sequences may be accomplished.

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