Patents by Inventor Wai Kwun Rossa Chiu
Wai Kwun Rossa Chiu has filed for patents to protect the following inventions. This listing includes patent applications that are pending as well as patents that have already been granted by the United States Patent and Trademark Office (USPTO).
-
Publication number: 20180282807Abstract: Systems, methods, and apparatus for determining at least a portion of fetal genome are provided. DNA fragments from a maternal sample (maternal and fetal DNA) can be analyzed to identify alleles at certain loci. The amounts of DNA fragments of the respective alleles at these loci can be analyzed together to determine relative amounts of the haplotypes for these loci and determine which haplotypes have been inherited from the parental genomes. Loci where the parents are a specific combination of homozygous and heterozygous can be analyzed to determine regions of the fetal genome. Reference haplotypes common in the population can be used along with the analysis of the DNA fragments of the maternal sample to determine the maternal and paternal genomes. Determination of mutations, a fractional fetal DNA concentration in a maternal sample, and a proportion of coverage of a sequencing of the maternal sample can also be provided.Type: ApplicationFiled: June 7, 2018Publication date: October 4, 2018Inventors: Yuk Ming Dennis Lo, Kwan Chee Chan, Wai Kwun Rossa Chiu, Charles Cantor
-
Publication number: 20180237858Abstract: Systems, methods, and apparatuses for performing a prenatal diagnosis of a sequence imbalance are provided. A shift (e.g. to a smaller size distribution) can signify an imbalance in certain circumstances. For example, a size distribution of fragments of nucleic acids from an at-risk chromosome can be used to determine a fetal chromosomal aneuploidy. A size ranking of different chromosomes can be used to determine changes of a rank of an at-risk chromosome from an expected ranking. Also, a difference between a statistical size value for one chromosome can be compared to a statistical size value of another chromosome to identify a significant shift in size. A genotype and haplotype of the fetus may also be determined using a size distribution to determine whether a sequence imbalance occurs in a maternal sample relative to a genotypes or haplotype of the mother, thereby providing a genotype or haplotype of the fetus.Type: ApplicationFiled: April 20, 2018Publication date: August 23, 2018Inventors: Yuk Ming Dennis Lo, Kwan Chee Chan, Wai Kwun Rossa Chiu, Wenli Zheng
-
Publication number: 20180157793Abstract: A fractional concentration of clinically-relevant DNA in a mixture of DNA from a biological sample is determined based on amounts of DNA fragments at multiple sizes. For example, the fractional concentration of fetal DNA in maternal plasma or tumor DNA in a patient's plasma can be determined. The size of DNA fragments in a sample is shown to be correlated with a proportion of fetal DNA and a proportion of tumor DNA, respectively. Calibration data points (e.g., as a calibration function) indicate a correspondence between values of a size parameter and the fractional concentration of the clinically-relevant DNA. For a given sample, a first value of a size parameter can be determined from the sizes of DNA fragments in a sample. A comparison of the first value to the calibration data points can provide the estimate of the fractional concentration of the clinically-relevant DNA.Type: ApplicationFiled: January 30, 2018Publication date: June 7, 2018Inventors: Yuk Ming Dennis Lo, Wai Kwun Rossa Chiu, Kwan Chee Chan, Wenli Zheng, Peiyong Jiang, Jiawei Liao
-
Patent number: 9982300Abstract: Systems, methods, and apparatuses for performing a prenatal diagnosis of a sequence imbalance are provided. A shift (e.g. to a smaller size distribution) can signify an imbalance in certain circumstances. For example, a size distribution of fragments of nucleic acids from an at-risk chromosome can be used to determine a fetal chromosomal aneuploidy. A size ranking of different chromosomes can be used to determine changes of a rank of an at-risk chromosome from an expected ranking. Also, a difference between a statistical size value for one chromosome can be compared to a statistical size value of another chromosome to identify a significant shift in size. A genotype and haplotype of the fetus may also be determined using a size distribution to determine whether a sequence imbalance occurs in a maternal sample relative to a genotypes or haplotype of the mother, thereby providing a genotype or haplotype of the fetus.Type: GrantFiled: November 25, 2013Date of Patent: May 29, 2018Assignee: The Chinese University of Hong KongInventors: Yuk Ming Dennis Lo, Kwan Chee Chan, Wai Kwun Rossa Chiu, Wenli Zheng
-
Patent number: 9892230Abstract: A fractional concentration of clinically-relevant DNA in a mixture of DNA from a biological sample is determined based on amounts of DNA fragments at multiple sizes. For example, the fractional concentration of fetal DNA in maternal plasma or tumor DNA in a patient's plasma can be determined. The size of DNA fragments in a sample is shown to be correlated with a proportion of fetal DNA and a proportion of tumor DNA, respectively. Calibration data points (e.g., as a calibration function) indicate a correspondence between values of a size parameter and the fractional concentration of the clinically-relevant DNA. For a given sample, a first value of a size parameter can be determined from the sizes of DNA fragments in a sample. A comparison of the first value to the calibration data points can provide the estimate of the fractional concentration of the clinically-relevant DNA.Type: GrantFiled: March 7, 2013Date of Patent: February 13, 2018Assignee: The Chinese University of Hong KongInventors: Yuk Ming Dennis Lo, Wai Kwun Rossa Chiu, Kwan Chee Chan, Wenli Zheng, Peiyong Jiang, Jiawei Liao
-
Patent number: 9862999Abstract: The present invention relates to new methods for diagnosing a pregnancy-associated disorder by analyzing fetal DNA present in the mother's blood. More specifically, this invention relies on the discovery that the maspin gene is differentially methylated in fetal DNA and in maternal DNA and provides these new diagnostic methods, which distinguish fetal DNA from maternal DNA and detect prenatal disorders based on abnormalities in fetal DNA level and methylation status.Type: GrantFiled: February 1, 2016Date of Patent: January 9, 2018Assignee: The Chinese University of Hong KongInventors: Yuk Ming Dennis Lo, Wai Kwun Rossa Chiu, Stephen Siu-Chung Chim, Yu-Kwan Tong, Chunming Ding
-
Publication number: 20170235877Abstract: A classification of a level of cancer in an organism is determined by analyzing a biological sample of the organism. The biological sample comprises clinically-relevant DNA and other DNA. At least some of the DNA is cell-free in the biological sample. An amount of a first set of DNA fragments from the biological sample corresponding to each of a plurality of sizes is measured. A first value of a first parameter is calculated based on the amounts of DNA fragments at the plurality of sizes. The first value is compared to a reference value. A classification of a level of cancer in the organism is determined based on the comparison.Type: ApplicationFiled: May 5, 2017Publication date: August 17, 2017Inventors: Yuk Ming Dennis LO, Wai Kwun Rossa Chiu, Kwan Chee Chan, Wenli Zheng, Peiyong Jiang, Jiawei Liao
-
Publication number: 20170132363Abstract: A classification of a level of cancer in an organism is determined by analyzing a biological sample of the organism. The biological sample comprises clinically-relevant DNA and other DNA. At least some of the DNA is cell-free in the biological sample. An amount of a first set of DNA fragments from the biological sample corresponding to each of a plurality of sizes is measured. A first value of a first parameter is calculated based on the amounts of DNA fragments at the plurality of sizes. The first value is compared to a reference value. A classification of a level of cancer in the organism is determined based on the comparison.Type: ApplicationFiled: January 20, 2017Publication date: May 11, 2017Inventors: Yuk Ming Dennis Lo, Wai Kwun Rossa Chiu, Kwan Chee Chan, Wenli Zheng, Peiyong Jiang, Jiawei Liao
-
Patent number: 9512480Abstract: Systems, methods, and apparatus for determining at least a portion of fetal genome are provided. DNA fragments from a maternal sample (maternal and fetal DNA) can be analyzed to identify alleles at certain loci. The amounts of DNA fragments of the respective alleles at these loci can be analyzed together to determine relative amounts of the haplotypes for these loci and determine which haplotypes have been inherited from the parental genomes. Loci where the parents are a specific combination of homozygous and heterozygous can be analyzed to determine regions of the fetal genome. Reference haplotypes common in the population can be used along with the analysis of the DNA fragments of the maternal sample to determine the maternal and paternal genomes. Determination of mutations, a fractional fetal DNA concentration in a maternal sample, and a proportion of coverage of a sequencing of the maternal sample can also be provided.Type: GrantFiled: May 15, 2013Date of Patent: December 6, 2016Assignees: The Chinese University of Hong Kong, Sequenom Inc.Inventors: Yuk Ming Dennis Lo, Kwan Chee Chan, Wai Kwun Rossa Chiu, Charles Cantor
-
Publication number: 20160258018Abstract: The present invention relates to new methods for diagnosing a pregnancy-associated disorder by analyzing fetal DNA present in the mother's blood. More specifically, this invention relies on the discovery that the maspin gene is differentially methylated in fetal DNA and in maternal DNA and provides these new diagnostic methods, which distinguish fetal DNA from maternal DNA and detect prenatal disorders based on abnormalities in fetal DNA level and methylation status.Type: ApplicationFiled: February 1, 2016Publication date: September 8, 2016Inventors: Yuk Ming Dennis Lo, Wai Kwun Rossa Chiu, Stephen Siu-Chung Chim, Yu-Kwan Tong, Chunming Ding
-
Publication number: 20160201134Abstract: Whether a fetus has an aneuploidy associated with a first chromosome is detected using ratios of alleles detected in a maternal sample having a mixture of maternal and fetal DNA. DNA from the sample is enriched for target regions associated with polymorphic loci and then sequenced. Polymorphic loci (e.g., single nucleotide polymorphisms) in the target regions with fetal-specific alleles are identified on a first chromosome and on one or more reference chromosomes. A first ratio of the fetal-specific alleles and shared alleles is determined for the loci on the first chromosome. A second ratio of the fetal-specific alleles and shared alleles is determined for the loci on the reference chromosome(s). A third ratio of the first and second ratio can be compared to a cutoff to determine whether an aneuploidy is present, and whether the aneuploidy is maternally-derived or paternally-derived.Type: ApplicationFiled: March 21, 2016Publication date: July 14, 2016Inventors: Jiawei Liao, Kwan Chee Chan, Wai Kwun Rossa Chiu, Yuk Ming Dennis Lo
-
Patent number: 9218449Abstract: This invention provides several ways of managing GC bias that occurs during seequencing and analysis of genomic DNA. Maternal plasma can be used as a source of fetal DNA for analysis. DNA segments or tags obtained from the plasma can be aligned with a chromosomal region of interest and with an artificial reference chromosome assembled from regions of the genome having matching GC content. This technology can be used, for example, to detect and evaluate aneuploidy and other chromosomal abnormalities.Type: GrantFiled: March 13, 2013Date of Patent: December 22, 2015Assignee: The Chinese University of Hong KongInventors: Yuk Ming Dennis Lo, Wai Kwun Rossa Chiu, Kwan Chee Chan, Wenli Zheng, Hao Sun, Zhang Chen
-
Publication number: 20140315200Abstract: Techniques are provided for determining inheritance of maternal and paternal haplotypes in preganncies with multiple fetuses. Maternal inheritance can be determined at loci where the mother is heterozygous and the paternally inherited alleles are known (e.g., the father is homozygous). Two types of loci may be used, where one type has the paternal allele appear on a first maternal haplotype, and another type has the paternal allele appear on a second maternal haplotype. Paternal inheritance can be determined from loci where the father is heterozygous and the maother is homozygous. Amounts of different alleles at each locus can be measured. A comparison of the amounts (e.g., using a fractional concentration of each allele and cutoffs) can be used to determine the haplotype inheritance. A haplotype can be linked to a condition of interest.Type: ApplicationFiled: March 17, 2014Publication date: October 23, 2014Applicant: The Chinese University of Hong KongInventors: Yuk Ming Dennis Lo, Wai Kwun Rossa Chiu, Kwan Chee Chan
-
Publication number: 20140302506Abstract: Disclosed herein are methods and kits for selectively amplifying, detecting or quantifying a DNA fragment with a specific end sequence, especially generated following restriction enzyme digestion. This method can be used, for example, to detect a hypomethylated DNA fragment. This methods and kits are especially useful in detecting or quantifying a hypomethylated fetal DNA fragment in a maternal plasma sample containing a corresponding hypermethylated maternal DNA fragment.Type: ApplicationFiled: April 29, 2014Publication date: October 9, 2014Applicant: The Chinese University of Hong KongInventors: Yuk Ming Dennis Lo, Yu Kwan Tong, Wai Kwun Rossa Chiu, Chunming Ding
-
Patent number: 8748100Abstract: Disclosed herein are methods and kits for selectively amplifying, detecting or quantifying a DNA fragment with a specific end sequence, especially generated following restriction enzyme digestion. This method can be used, for example, to detect a hypomethylated DNA fragment. This methods and kits are especially useful in detecting or quantifying a hypomethylated fetal DNA fragment in a maternal plasma sample containing a corresponding hypermethylated maternal DNA fragment.Type: GrantFiled: August 30, 2007Date of Patent: June 10, 2014Assignee: The Chinese University of Hong KongInventors: Yuk Ming Dennis Lo, Yu Kwan Tong, Wai Kwun Rossa Chiu, Chunming Ding
-
Patent number: 8741811Abstract: Biological samples including cell-free DNA fragments are analyzed to identify imbalances in chromosomal regions, e.g., due to deletions and/or amplifications in a tumor. Multiple loci are used for each chromosomal region. Such imbalances can then be used to diagnose (screen) a patient for cancer, as well as prognosticate a patient with cancer, or to detect the presence or to monitor the progress of a premalignant condition in a patient. The severity of an imbalance as well as the number of regions exhibiting an imbalance can be used. A systematic analysis of non-overlapping segments of a genome can provide a general screening tool for a sample. Additionally, a patient can be tested over time to track severity of each of one or more chromosomal regions and a number of chromosomal regions to enable screening and prognosticating, as well as monitoring of progress (e.g. after treatment).Type: GrantFiled: November 30, 2011Date of Patent: June 3, 2014Assignee: The Chinese University of Hong KongInventors: Yuk Ming Dennis Lo, Kwan Chee Chan, Wai Kwun Rossa Chiu, Peiyong Jiang
-
Publication number: 20140080720Abstract: Systems, methods, and apparatuses for performing a prenatal diagnosis of a sequence imbalance are provided. A shift (e.g. to a smaller size distribution) can signify an imbalance in certain circumstances. For example, a size distribution of fragments of nucleic acids from an at-risk chromosome can be used to determine a fetal chromosomal aneuploidy. A size ranking of different chromosomes can be used to determine changes of a rank of an at-risk chromosome from an expected ranking. Also, a difference between a statistical size value for one chromosome can be compared to a statistical size value of another chromosome to identify a significant shift in size. A genotype and haplotype of the fetus may also be determined using a size distribution to determine whether a sequence imbalance occurs in a maternal sample relative to a genotypes or haplotype of the mother, thereby providing a genotype or haplotype of the fetus.Type: ApplicationFiled: November 25, 2013Publication date: March 20, 2014Applicant: The Chinese University of Hong KongInventors: Yuk Ming Dennis Lo, Kwan Chee Chan, Wai Kwun Rossa Chiu, Wenli Zheng
-
Publication number: 20140019064Abstract: Methods, apparatuses, and system are provided for analyzing a maternal sample to determine whether a male fetus of a pregnant female has inherited an X-linked mutation from the mother. A percentage of fetal DNA in the sample is obtained, and cutoff values for the two possibilities (fetus inherits mutant or normal allele) are determined. A proportion of mutant alleles relative to a normal allele on the X-chromosome can then be compared to the cutoff values to make a classification of which allele is inherited. Alternatively, a number of alleles from a target region on the X-chromosome can be compared to a number of alleles from a reference region on the X-chromosome to identify a deletion or amplification. The fetal DNA percentage can be computed by counting reactions with a fetal-specific allele, and correcting the number to account for a statistical distribution among the reactions.Type: ApplicationFiled: January 5, 2012Publication date: January 16, 2014Applicant: THE CHINESE UNIVERSITY OF HONG KONGInventors: Yuk Ming Dennis Lo, Wai kwun Rossa Chiu, Kwan Chee Chan, Bo Yin Tsui
-
Patent number: 8620593Abstract: Systems, methods, and apparatuses for performing a prenatal diagnosis of a sequence imbalance are provided. A shift (e.g. to a smaller size distribution) can signify an imbalance in certain circumstances. For example, a size distribution of fragments of nucleic acids from an at-risk chromosome can be used to determine a fetal chromosomal aneuploidy. A size ranking of different chromosomes can be used to determine changes of a rank of an at-risk chromosome from an expected ranking. Also, a difference between a statistical size value for one chromosome can be compared to a statistical size value of another chromosome to identify a significant shift in size. A genotype and haplotype of the fetus may also be determined using a size distribution to determine whether a sequence imbalance occurs in a maternal sample relative to a genotypes or haplotype of the mother, thereby providing a genotype or haplotype of the fetus.Type: GrantFiled: November 5, 2010Date of Patent: December 31, 2013Assignee: The Chinese University of Hong KongInventors: Yuk Ming Dennis Lo, Kwan Chee Chan, Wai Kwun Rossa Chiu, Wenli Zheng
-
Publication number: 20130323731Abstract: Systems, methods, and apparatus for determining at least a portion of fetal genome are provided. DNA fragments from a maternal sample (maternal and fetal DNA) can be analyzed to identify alleles at certain loci. The amounts of DNA fragments of the respective alleles at these loci can be analyzed together to determine relative amounts of the haplotypes for these loci and determine which haplotypes have been inherited from the parental genomes. Loci where the parents are a specific combination of homozygous and heterozygous can be analyzed to determine regions of the fetal genome. Reference haplotypes common in the population can be used along with the analysis of the DNA fragments of the maternal sample to determine the maternal and paternal genomes. Determination of mutations, a fractional fetal DNA concentration in a maternal sample, and a proportion of coverage of a sequencing of the maternal sample can also be provided.Type: ApplicationFiled: May 15, 2013Publication date: December 5, 2013Applicant: The Chinese University of Hong KongInventors: Yuk Ming Dennis Lo, Kwan Chee Chan, Wai Kwun Rossa Chiu, Charles Cantor