Patents by Inventor Rossa Wai Kwun Chiu
Rossa Wai Kwun 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).
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Publication number: 20220112554Abstract: An amount of mitochondrial DNA molecules relative to an amount of nuclear DNA molecules is determined in a biological sample, and the relative amount is used for various purposes, e.g., screening, detection, prognostication or monitoring of various physiological and pathological conditions. As examples, an amount of mitochondrial DNA can be used to estimate a concentration of DNA of a tissue type, such as a fetal DNA concentration, tumor DNA concentration, or a concentration of DNA in the biological sample derived from a non-hematopoietic tissue source. Sequencing techniques can be used to determine a mitochondrial DNA concentration in a sample for an accurate detection of a level of cancer. A level of an auto-immune disease is also determined using a relative amount of mitochondrial DNA molecules compared nuclear DNA molecules.Type: ApplicationFiled: December 22, 2021Publication date: April 14, 2022Inventors: Yuk-Ming Dennis Lo, Rossa Wai Kwun Chiu, Kwan Chee Chan, Peiyong Jiang
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Patent number: 11274347Abstract: Systems, methods, and apparatuses can determine and use methylation profiles of various tissues and samples. Examples are provided. A methylation profile can be deduced for fetal/tumor tissue based on a comparison of plasma methylation (or other sample with cell-free DNA) to a methylation profile of the mother/patient. A methylation profile can be determined for fetal/tumor tissue using tissue-specific alleles to identify DNA from the fetus/tumor when the sample has a mixture of DNA. A methylation profile can be used to determine copy number variations in genome of a fetus/tumor. Methylation markers for a fetus have been identified via various techniques. The methylation profile can be determined by determining a size parameter of a size distribution of DNA fragments, where reference values for the size parameter can be used to determine methylation levels. Additionally, a methylation level can be used to determine a level of cancer.Type: GrantFiled: July 12, 2017Date of Patent: March 15, 2022Assignee: The Chinese University of Hong KongInventors: Yuk-Ming Dennis Lo, Rossa Wai Kwun Chiu, Kwan Chee Chan, Miu Fan Lun, Wai Man Chan, Peiyong Jiang
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Publication number: 20220064714Abstract: Size-band analysis is used to determine whether a chromosomal region exhibits a copy number aberration or an epigenetic alteration. Multiple size ranges may be analyzed instead of focusing on specific sizes. By using multiple size ranges instead of specific sizes, methods may analyze more sequence reads and may be able to determine whether a chromosomal region exhibits a copy number aberration even when clinically-relevant DNA may be a low fraction of the biological sample. Using multiple ranges may allow for the use of all sequence reads from a genomic region, rather than a selected subset of reads in the genomic region. The accuracy of analysis may be increased with higher sensitivity at similar or higher specificity. Analysis may include fewer sequencing reads to achieve the same accuracy, resulting in a more efficient process.Type: ApplicationFiled: November 8, 2021Publication date: March 3, 2022Inventors: Yuk-Ming Dennis Lo, Rossa Wai Kwun Chiu, Kwan Chee Chan, Peiyong Jiang
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Patent number: 11261494Abstract: A frequency of somatic mutations in a biological sample (e.g., plasma or serum) of a subject undergoing screening or monitoring for cancer, can be compared with that in the constitutional DNA of the same subject. A parameter can derived from these frequencies and used to determine a classification of a level of cancer. False positives can be filtered out by requiring any variant locus to have at least a specified number of variant sequence reads (tags), thereby providing a more accurate parameter. The relative frequencies for different variant loci can be analyzed to determine a level of heterogeneity of tumors in a patient.Type: GrantFiled: March 13, 2013Date of Patent: March 1, 2022Assignee: The Chinese University of Hong KongInventors: Yuk-Ming Dennis Lo, Rossa Wai Kwun Chiu, Kwan Chee Chan, Peiyong Jiang
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Patent number: 11242559Abstract: An amount of mitochondrial DNA molecules relative to an amount of nuclear DNA molecules is determined in a biological sample, and the relative amount is used for various purposes, e.g., screening, detection, prognostication or monitoring of various physiological and pathological conditions. As examples, an amount of mitochondrial DNA can be used to estimate a concentration of DNA of a tissue type, such as a fetal DNA concentration, tumor DNA concentration, or a concentration of DNA in the biological sample derived from a non-hematopoietic tissue source. Sequencing techniques can be used to determine a mitochondrial DNA concentration in a sample for an accurate detection of a level of cancer. A level of an auto-immune disease is also determined using a relative amount of mitochondrial DNA molecules compared nuclear DNA molecules.Type: GrantFiled: January 12, 2016Date of Patent: February 8, 2022Assignee: The Chinese University of Hong KongInventors: Yuk-Ming Dennis Lo, Rossa Wai Kwun Chiu, Kwan Chee Chan, Peiyong Jiang
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Publication number: 20220010353Abstract: Various embodiments are directed to using nuclease expression in tissues that influences cell-free DNA end signatures/motifs and size of overhang between DNA strands. Embodiments can identify a nuclease that is being differentially regulated in abnormal cells relative to normal cells. Embodiments can determine that the nuclease preferentially cuts DNA into DNA molecules having: (i) a particular sequence end signature; or (ii) a specified length of overhang between a first strand and a second strand. A parameter can be determined for a biological sample based on an amount of DNA molecules that include an end sequence corresponding to the particular sequence end signature and/or a measured property correlating to the specified length of overhang. The parameter can be used to determine a characteristic of a tissue type, a fractional concentration of clinically-relevant DNA molecules, or a level of abnormality of a tissue type in the biological sample.Type: ApplicationFiled: July 13, 2021Publication date: January 13, 2022Inventors: Yuk-Ming Dennis Lo, Rossa Wai Kwun Chiu, Kwan Chee Chan, Peiyong Jiang, Wing Yan Chan, Wai Kei Lam, Diana Siao Cheng Han, Wenlei Peng, Chen Ding
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Publication number: 20210363571Abstract: Systems and methods for using determination of base modification in analyzing nucleic acid molecules and acquiring data for analysis of nucleic acid molecules are described herein. Base modifications may include methylations. Methods to determine base modifications may include using features derived from sequencing. These features may include the pulse width of an optical signal from sequencing bases, the interpulse duration of bases, and the identity of the bases. Machine learning models can be trained to detect the base modifications using these features. The relative modification or methylation levels between haplotypes may indicate a disorder. Modification or methylation statuses may also be used to detect chimeric molecules.Type: ApplicationFiled: July 19, 2021Publication date: November 25, 2021Inventors: Yuk-Ming Dennis Lo, Rossa Wai Kwun Chiu, Kwan Chee Chan, Peiyong Jiang, Suk Hang Cheng, Wenlei Peng, On Yee Tse
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Patent number: 11168370Abstract: Embodiments are related to the accurate detection of somatic mutations in the plasma (or other samples containing cell-free DNA) of cancer patients and for subjects being screened for cancer. The detection of these molecular markers would be useful for the screening, detection, monitoring, management, and prognostication of cancer patients. For example, a mutational load can be determined from the identified somatic mutations, and the mutational load can be used to screen for any or various types of cancers, where no prior knowledge about a tumor or possible cancer of the subject may be required. Embodiments can be useful for guiding the use of therapies (e.g. targeted therapy, immunotherapy, genome editing, surgery, chemotherapy, embolization therapy, anti-angiogenesis therapy) for cancers. Embodiments are also directed to identifying de novo mutations in a fetus by analyzing a maternal sample having cell-free DNA from the fetus.Type: GrantFiled: January 22, 2019Date of Patent: November 9, 2021Assignee: The Chinese University of Hong KongInventors: Yuk-Ming Dennis Lo, Rossa Wai Kwun Chiu, Kwan Chee Chan, Peiyong Jiang
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Patent number: 11168356Abstract: Size-band analysis is used to determine whether a chromosomal region exhibits a copy number aberration or an epigenetic alteration. Multiple size ranges may be analyzed instead of focusing on specific sizes. By using multiple size ranges instead of specific sizes, methods may analyze more sequence reads and may be able to determine whether a chromosomal region exhibits a copy number aberration even when clinically-relevant DNA may be a low fraction of the biological sample. Using multiple ranges may allow for the use of all sequence reads from a genomic region, rather than a selected subset of reads in the genomic region. The accuracy of analysis may be increased with higher sensitivity at similar or higher specificity. Analysis may include fewer sequencing reads to achieve the same accuracy, resulting in a more efficient process.Type: GrantFiled: November 1, 2018Date of Patent: November 9, 2021Assignees: The Chinese University of Hong Kong, GRAIL, Inc.Inventors: Yuk-Ming Dennis Lo, Rossa Wai Kwun Chiu, Kwan Chee Chan, Peiyong Jiang
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Patent number: 11142799Abstract: Methods, systems, and apparatus determine whether a first chromosomal region exhibits a deletion or an amplification associated with cancer in a sample from a subject (e.g., where the sample includes a mixture of cell-free DNA from tumor cells and non-malignant cells. Nucleic acid molecules of the biological sample are sequenced. Respective amounts of a clinically-relevant chromosomal region and of background chromosomal region(s) are determined from results of the sequencing. A parameter derived from these amounts (e.g. a ratio) is compared to one or more cutoff values, thereby determining a classification of whether first chromosomal region exhibits a deletion or an amplification associated with cancer.Type: GrantFiled: May 5, 2017Date of Patent: October 12, 2021Assignee: The Chinese University of Hong KongInventors: Yuk-Ming Dennis Lo, Rossa Wai Kwun Chiu, Kwan Chee Chan
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Publication number: 20210265007Abstract: Methods and systems described herein involve using long cell-free DNA fragments to analyze a biological sample from a pregnant subject. The status of methylated CpG sites and single nucleotide polymorphisms (SNPs) is often used to analyze DNA fragments of a biological sample. A CpG site and a SNP are typically separated from the nearest CpG site or SNP by hundreds or thousands of base pairs. Finding two or more consecutive CpG sites or SNPs on most cell-free DNA fragments is improbable or impossible. Cell-free DNA fragments longer than 600 bp may include multiple CpG sites and/or SNPs. The presence of multiple CpG sites and/or SNPs on long cell-free DNA fragments may allow for analysis than with short cell-free DNA fragments alone. The long cell-free DNA fragments can be used to identify a tissue of origin and/or to provide information on a fetus in a pregnant female.Type: ApplicationFiled: February 5, 2021Publication date: August 26, 2021Inventors: Yuk-Ming Dennis Lo, Rossa Wai Kwun Chiu, Kwan Chee Chan, Peiyong Jiang, Suk Hang Cheng, Cheuk Yin Yu, Yee Ting Cheung, Wenlei Peng
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Publication number: 20210254142Abstract: Methods and systems described herein involve using long cell-free DNA fragments to analyze a biological sample from a pregnant subject. The status of methylated CpG sites and single nucleotide polymorphisms (SNPs) is often used to analyze DNA fragments of a biological sample. A CpG site and a SNP are typically separated from the nearest CpG site or SNP by hundreds or thousands of base pairs. Finding two or more consecutive CpG sites or SNPs on most cell-free DNA fragments is improbable or impossible. Cell-free DNA fragments longer than 600 bp may include multiple CpG sites and/or SNPs. The presence of multiple CpG sites and/or SNPs on long cell-free DNA fragments may allow for analysis than with short cell-free DNA fragments alone. The long cell-free DNA fragments can be used to identify a tissue of origin and/or to provide information on a fetus in a pregnant female.Type: ApplicationFiled: March 9, 2021Publication date: August 19, 2021Inventors: Yuk-Ming Dennis Lo, Rossa Wai Kwun Chiu, Kwan Chee Chan, Peiyong Jiang, Suk Hang Cheng, Cheuk Yin Yu, Yee Ting Cheung, Wenlei Peng
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Patent number: 11091794Abstract: Systems and methods for using determination of base modification in analyzing nucleic acid molecules and acquiring data for analysis of nucleic acid molecules are described herein. Base modifications may include methylations. Methods to determine base modifications may include using features derived from sequencing. These features may include the pulse width of an optical signal from sequencing bases, the interpulse duration of bases, and the identity of the bases. Machine learning models can be trained to detect the base modifications using these features. The relative modification or methylation levels between haplotypes may indicate a disorder. Modification or methylation statuses may also be used to detect chimeric molecules.Type: GrantFiled: August 17, 2020Date of Patent: August 17, 2021Assignee: The Chinese University of Hong KongInventors: Yuk-Ming Dennis Lo, Rossa Wai Kwun Chiu, Kwan Chee Chan, Peiyong Jiang, Suk Hang Cheng, Wenlei Peng, On Yee Tse
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Publication number: 20210238668Abstract: The present disclosure describes techniques for measuring quantities (e.g., relative frequencies) of end motif pairs of cell-free DNA fragments in a biological sample of an organism for measuring a property of the sample (e.g., fractional concentration of clinically-relevant DNA) and/or determining a pathology of the organism based on such measurements. Different tissue types exhibit different patterns for the relative frequencies of the end motif pairs. The present disclosure provides various uses for measurements of the relative frequencies of end motif pairs of cell-free DNA, e.g., in mixtures of cell-free DNA from various tissues. DNA from certain tissue(s) may be referred to as clinically-relevant DNA.Type: ApplicationFiled: January 7, 2021Publication date: August 5, 2021Inventors: Yuk-Ming Dennis Lo, Rossa Wai Kwun Chiu, Diana Siao Cheng Han, Meng Ni
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Patent number: 11062789Abstract: The contributions of different tissues to a DNA mixture are determined using methylation levels at particular genomic sites. Tissue-specific methylation levels of M tissue types can be used to deconvolve mixture methylation levels measured in the DNA mixture, to determine fraction contributions of each of the M tissue types. Various types of genomic sites can be chosen to have particular properties across tissue types and across individuals, so as to provide increased accuracy in determining contributions of the various tissue types. The fractional contributions can be used to detect abnormal contributions of a particular tissue, indicating a disease state for the tissue. A differential in fractional contributions for different sizes of DNA fragments can also be used to identify a diseased state of a particular tissue. A sequence imbalance for a particular chromosomal region can be detected in a particular tissue, e.g., identifying a location of a tumor.Type: GrantFiled: July 20, 2015Date of Patent: July 13, 2021Assignee: The Chinese University of Hong KongInventors: Rossa Wai Kwun Chiu, Kwan Chee Chan, Yuk-Ming Dennis Lo, Peiyong Jiang, Kun Sun
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Publication number: 20210189494Abstract: Various methods, apparatuses, and systems are provided for detecting a genetic disorder in a gene associated with a nuclease, for determining an efficacy of a dosage of an anticoagulant, and for monitoring an activity of a nuclease. Measured parameter values can be compared to a reference value to determine classifications of a genetic disorder, efficiency, or activity. An amount of a particular base (e.g., in an end motif) at fragment ends, an amount of a particular base at fragment ends of a particular size, or a total amount of cell-free DNA fragments (e.g., as a concentration) can be used. Certain samples may be treated with an anticoagulant, and different incubation times can be used for certain methods.Type: ApplicationFiled: December 18, 2020Publication date: June 24, 2021Inventors: Yuk-Ming Dennis Lo, Rossa Wai Kwun Chiu, Diana Siao Cheng Han, Meng Ni
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Publication number: 20210125688Abstract: Systems, methods, and apparatuses can determine and use methylation profiles of various tissues and samples. Examples are provided. A methylation profile can be deduced for fetal/tumor tissue based on a comparison of plasma methylation (or other sample with cell-free DNA) to a methylation profile of the mother/patient. A methylation profile can be determined for fetal/tumor tissue using tissue-specific alleles to identify DNA from the fetus/tumor when the sample has a mixture of DNA. A methylation profile can be used to determine copy number variations in genome of a fetus/tumor. Methylation markers for a fetus have been identified via various techniques. The methylation profile can be determined by determining a size parameter of a size distribution of DNA fragments, where reference values for the size parameter can be used to determine methylation levels. Additionally, a methylation level can be used to determine a level of cancer.Type: ApplicationFiled: December 28, 2020Publication date: April 29, 2021Inventors: Yuk-Ming Dennis Lo, Rossa Wai Kwun Chiu, Kwan Chee Chan, Miu Fan Lun, Wai Man Chan, Peiyong Jiang
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Publication number: 20210047679Abstract: Systems and methods for using determination of base modification in analyzing nucleic acid molecules and acquiring data for analysis of nucleic acid molecules are described herein. Base modifications may include methylations. Methods to determine base modifications may include using features derived from sequencing. These features may include the pulse width of an optical signal from sequencing bases, the interpulse duration of bases, and the identity of the bases. Machine learning models can be trained to detect the base modifications using these features. The relative modification or methylation levels between haplotypes may indicate a disorder. Modification or methylation statuses may also be used to detect chimeric molecules.Type: ApplicationFiled: August 17, 2020Publication date: February 18, 2021Inventors: Yuk-Ming Dennis Lo, Rossa Wai Kwun Chiu, Kwan Chee Chan, Peiyong Jiang, Suk Hang Cheng, Wenlei Peng, On Yee Tse
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Publication number: 20200407799Abstract: Techniques are provided for analyzing circular DNA in a biological sample (e.g., including cell-free DNA, such as plasma). For example, to measure circular DNA, cleaving can be performed to linearize the circular DNA so that they may be sequenced. Example cleaving techniques include restriction enzymes and transposases. Then, one or more criteria can be used to identify linearized DNA molecules, e.g., so as to differentiate from linear DNA molecules. An example criterion is mapping a pair of reversed end sequences to a reference genome. Another example criterion is identification of a cutting tag, e.g., associated with a restriction enzyme or an adapter sequence added by a transposase. Once circular DNA molecules (e.g., eccDNA and circular mitochondrial DNA) are identified, they may be analyzed (e.g., to determine a count, size profile, and/or methylation) to measure a property of the biological sample, including genetic properties and level of a disease.Type: ApplicationFiled: March 25, 2020Publication date: December 31, 2020Inventors: Yuk-Ming Dennis Lo, Rossa Wai Kwun Chiu, Kwan Chee Chan, Peiyong Jiang, Lu Ji, Tsz Kwan Sin, Haiqiang Zhang, Jiaen Deng
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Publication number: 20200385811Abstract: Techniques are provided for detecting hematological disorders using cell-free DNA in a blood sample, e.g., using plasma or serum. For example, an assay can target one or more differentially-methylated regions specific to a particular hematological cell lineage (e.g., erythroblasts). A methylation level can be quantified from the assay to determine an amount of methylated or unmethylated DNA fragments in a cell-free mixture of the blood sample. The methylation level can be compared to one or more cutoff values, e.g., that correspond to a normal range for the particular hematological cell lineage as part of determining a level of a hematological disorder.Type: ApplicationFiled: August 19, 2020Publication date: December 10, 2020Inventors: Yuk-Ming Dennis Lo, Rossa Wai Kwun Chiu, Kwan Chee Chan, Kun Sun