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: 20240093298Abstract: Systems, methods, and apparatuses are provided for diagnosing auto-immune diseases such as systemic lupus erythematosus (SLE) based on the sizes, methylation levels, and/or genomic characteristics of circulating DNA molecules. Patients provide blood or other tissue samples containing cell-free nucleic molecules for analysis. Massively parallel and/or methylation-aware sequencing can be used to determine the sizes and methylation levels of individual DNA molecules and identify the number of molecules originating from different genomic regions.Type: ApplicationFiled: April 21, 2023Publication date: March 21, 2024Inventors: Yuk-Ming Dennis Lo, Rossa Wai Kwun Chiu, Rebecca Wing Yan Chan, Lai Shan Tam
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Patent number: 11926821Abstract: The quality of cell-free DNA for analysis is improved by techniques described herein. Cell-free DNA may include DNA with defects that do not allow for analysis of those DNA with techniques such as sequencing and targeted capture enrichment. These defects may be defects within the strands of the DNA and not present at the ends of the DNA. These intrastrand defects in cell-free DNA can be repaired. The repair of the defects in cell-free DNA may then allow for these repaired cell-free DNA to be analyzed by techniques, including sequencing and targeted capture enrichment.Type: GrantFiled: October 21, 2019Date of Patent: March 12, 2024Assignee: The Chinese University of Hong KongInventors: Yuk-Ming Dennis Lo, Cheuk Ho Tsang, Peiyong Jiang, Si Long Vong, Rossa Wai Kwun Chiu
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Patent number: 11923046Abstract: Disclosed herein are methods, systems, and apparatus for detecting microamplifications or microdeletions in the genome of a fetus. In some embodiments, the method comprises receiving sequence tags for each of a plurality of DNA fragments in a biological sample; determining genomic positions for the sequence tags; determining whether the density of DNA in each of a plurality of genomic regions is aberrantly high or low; identifying as a microamplification a set of consecutive genomic regions having aberrantly high density; and identifying as a microdeletion a set of consecutive genomic regions having aberrantly low density. The biological sample may be a blood sample obtained noninvasively from a female subject pregnant with the fetus.Type: GrantFiled: February 7, 2020Date of Patent: March 5, 2024Assignee: The Chinese University of Hong KongInventors: Yuk Ming Dennis Lo, Kwan Chee Chan, Peiyong Jiang, Cheuk Yin Jandy Yu, Rossa Wai Kwun Chiu
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Patent number: 11884966Abstract: Provided herein are compositions comprising tissue-specific markers for identifying a tissue of origin of a cell-free nucleic acid, e.g., a cell-free DNA molecule. Also provided herein are methods, compositions, and systems for identifying a tissue of origin of a cell-free nucleic acid by determining an absolute amount of cell-free nucleic acids comprising the tissue-specific marker. Also provided herein are methods, compositions, and systems for detecting a cancer in a tissue of an organism by analyzing tissue-specific markers.Type: GrantFiled: March 15, 2019Date of Patent: January 30, 2024Assignee: GRAIL, LLCInventors: Yuk-Ming Dennis Lo, Rossa Wai Kwun Chiu, Kwan Chee Chan, Wanxia Gai, Lu Ji
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Publication number: 20240018570Abstract: 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: September 11, 2023Publication date: January 18, 2024Inventors: 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: 11873527Abstract: 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: GrantFiled: August 19, 2020Date of Patent: January 16, 2024Assignee: The Chinese University of Hong KongInventors: Yuk-Ming Dennis Lo, Rossa Wai Kwun Chiu, Kwan Chee Chan, Kun Sun
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Publication number: 20240011105Abstract: Various embodiments are directed to detecting infection-causing microbial cell-free DNA from a biological sample based on their size profiles and/or end signatures, in which the detection of infection-causing microbial DNA can be performed without no template control (NTC) samples. Embodiments can include identifying the infection-causing pathogen-derived microbial DNA based on sizes of microbial cell-free DNA molecules. Embodiments can also include identifying from the infection-causing pathogen-derived microbial DNA based on end signatures of microbial cell-free DNA molecules. Embodiments can also include applying a machine-learning algorithm to a plurality of vectors that represent end signatures of the microbial cell-free DNA molecules, to identify the infection-causing pathogen-derived microbial DNA. By detecting the infection-causing pathogen-derived microbial DNA, a level of infection for the biological sample can be predicted.Type: ApplicationFiled: July 8, 2022Publication date: January 11, 2024Inventors: Yuk-Ming Dennis Lo, Kwan Chee Chan, Rossa Wai Kwun Chiu, Wai Kei Lam, Peiyong Jiang, Guangya Wang
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Publication number: 20230374602Abstract: Fragmentation of cell-free DNA molecules is measured and used for various purposes, including determining methylation, e.g., at a particular site of a DNA molecule, at a particular genomic site in a reference genome for a biological sample (e.g., plasma, serum, urine, saliva) of cell-free DNA of a subject, or for a particular region in the reference genome for the biological sample (also just referred to as a sample). Various types of fragmentation measurements can be used, e.g., end motifs and cleavage profiles. Another purpose is determining a fractional concentration of DNA of a particular tissue type (e.g., clinically-relevant DNA). Another purpose is determining a pathology of a subject using a biological sample including cell-free DNA. The cell-free DNA can be of the subject or of a pathogen (e.g., a virus) in the subject's sample. Sites/regions that are hypermethylated, hypomethylated, 5hmC-enriched, and 5hmC-depleted for a particular tissue type can be used.Type: ApplicationFiled: March 6, 2023Publication date: November 23, 2023Inventors: Yuk-Ming Dennis Lo, Rossa Wai Kwun Chiu, Kwan Chee Chan, Peiyong Jiang, Qing Zhou, Guannan Kang, Rong Qiao, Lu Ji
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Publication number: 20230374601Abstract: Fragmentation of cell-free DNA molecules is measured and used for various purposes, including determining methylation, e.g., at a particular site of a DNA molecule, at a particular genomic site in a reference genome for a biological sample (e.g., plasma, serum, urine, saliva) of cell-free DNA of a subject, or for a particular region in the reference genome for the biological sample (also just referred to as a sample). Various types of fragmentation measurements can be used, e.g., end motifs and cleavage profiles. Another purpose is determining a fractional concentration of DNA of a particular tissue type (e.g., clinically-relevant DNA). Another purpose is determining a pathology of a subject using a biological sample including cell-free DNA. The cell-free DNA can be of the subject or of a pathogen (e.g., a virus) in the subject's sample. Sites/regions that are hypermethylated, hypomethylated, 5hmC-enriched, and 5hmC-depleted for a particular tissue type can be used.Type: ApplicationFiled: March 6, 2023Publication date: November 23, 2023Inventors: Yuk-Ming Dennis Lo, Rossa Wai Kwun Chiu, Kwan Chee Chan, Peiyong Jiang, Qing Zhou, Guannan Kang, Rong Qiao, Lu Ji
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Publication number: 20230366007Abstract: Cell-free nucleic acid from extracellular particles (EPs) is analyzed. A sample can be purified for the extracellular particles. As examples, the purification can include centrifuging, washing, and a nuclease treatment. To increase the fetal fraction, the purification can enrich a sample for a certain type of EPs (e.g., long EPs). In this manner, a desired population of particles can be selected for the analysis of their nucleic acids. As part of an analysis of the nucleic acid molecules (fragments) from an enriched sample, nucleic acid molecules greater than a certain size can be selected, which can increase genetic and/or epigenetic informativeness, without an adverse effect (e.g., the reduction of fetal DNA fraction). The long nucleic acid fragments can be analyzed in various ways, including using short read sequencing techniques that perform fragmentation before sequencing and using long read sequencing techniques.Type: ApplicationFiled: May 9, 2023Publication date: November 16, 2023Inventors: Yuk-Ming Dennis Lo, Rossa Wai Kwun Chiu, Kwan Chee Chan, Pelyong Jiang, Qing Zhou
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Publication number: 20230323462Abstract: Methods, systems, and apparatus are provided for determining whether a nucleic acid sequence imbalance exists within a biological sample. One or more cutoff values for determining an imbalance of, for example, the ratio of the two sequences (or sets of sequences) are chosen. The cutoff value may be determined based at least in part on the percentage of fetal DNA in a sample, such as maternal plasma, containing a background of maternal nucleic acid sequences. The percentage of fetal DNA can be calculated from the same or different data used to determine the cutoff value, and can use a locus where the mother is homozygous and the fetus is heterozygous. The cutoff value may be determined using many different types of methods, such as sequential probability ratio testing (SPRT).Type: ApplicationFiled: June 16, 2023Publication date: October 12, 2023Inventors: Yuk-Ming Dennis Lo, Rossa Wai Kwun Chiu, Kwan Chee Chan, Benny Chung Ying Zee, Ka Chun Chong
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Publication number: 20230313314Abstract: Fragmentation of cell-free DNA molecules is measured and used for various purposes, including determining methylation, e.g., at a particular site of a DNA molecule, at a particular genomic site in a reference genome for a biological sample (e.g., plasma, serum, urine, saliva) of cell-free DNA of a subject, or for a particular region in the reference genome for the biological sample (also just referred to as a sample). Various types of fragmentation measurements can be used, e.g., end motifs and cleavage profiles. Another purpose is determining a fractional concentration of DNA of a particular tissue type (e.g., clinically-relevant DNA). Another purpose is determining a pathology of a subject using a biological sample including cell-free DNA. The cell-free DNA can be of the subject or of a pathogen (e.g., a virus) in the subject's sample. Sites/regions that are hypermethylated, hypomethylated, 5hmC-enriched, and 5hmC-depleted for a particular tissue type can be used.Type: ApplicationFiled: February 7, 2023Publication date: October 5, 2023Inventors: Yuk-Ming Dennis Lo, Rossa Wai Kwun Chiu, Kwan Chee Chan, Peiyong Jiang, Qing Zhou, Guannan Kang, Rong Qiao, Lu Ji
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Publication number: 20230279498Abstract: Methods and systems described herein include using various characteristics of cell-free DNA molecules to determine a property of a biological sample or a subject. Such characteristics can include size (e.g., where characteristic is of long cell-free DNA molecules), methylation, and end motifs. The method includes determining disease classification and/or predicting tissue of origin. In some instances, the characteristics includes determining an amount of long cell-free DNA molecules, and the disease classification can be based on the determined amount. The characteristics can also include identifying methylation pattern of a cell-free DNA molecule, then comparing the methylation pattern to a reference pattern to predict the tissue origin. In some instances, the methylation-pattern analysis includes using a trained machine-learning model.Type: ApplicationFiled: November 23, 2022Publication date: September 7, 2023Inventors: Yuk-Ming Dennis Lo, Rossa Wai Kwun Chiu, Kwan Chee Chan, Peiyong Jiang, Lok Yee Choy
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Patent number: 11725245Abstract: Methods, systems, and apparatus are provided for determining whether a nucleic acid sequence imbalance exists within a biological sample. One or more cutoff values for determining an imbalance of, for example, the ratio of the two sequences (or sets of sequences) are chosen. The cutoff value may be determined based at least in part on the percentage of fetal DNA in a sample, such as maternal plasma, containing a background of maternal nucleic acid sequences. The percentage of fetal DNA can be calculated from the same or different data used to determine the cutoff value, and can use a locus where the mother is homozygous and the fetus is heterozygous. The cutoff value may be determined using many different types of methods, such as sequential probability ratio testing (SPRT).Type: GrantFiled: January 11, 2019Date of Patent: August 15, 2023Assignee: The Chinese University of Hong KongInventors: Yuk-Ming Dennis Lo, Rossa Wai Kwun Chiu, Kwan Chee Chan, Benny Chung Ying Zee, Ka Chun Chong
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Publication number: 20230197201Abstract: Factors affecting the fragmentation pattern of cell-free DNA (e.g., plasma DNA) and the applications, including those in molecular diagnostics, of the analysis of cell-free DNA fragmentation patterns are described. Various applications can use a property of a fragmentation pattern to determine a proportional contribution of a particular tissue type, to determine a genotype of a particular tissue type (e.g., fetal tissue in a maternal sample or tumor tissue in a sample from a cancer patient), and/or to identify preferred ending positions for a particular tissue type, which may then be used to determine a proportional contribution of a particular tissue type.Type: ApplicationFiled: February 15, 2023Publication date: June 22, 2023Inventors: Yuk-Ming Dennis Lo, Rossa Wai Kwun Chiu, Kwan Chee Chan, Peiyong Jiang
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Publication number: 20230193360Abstract: 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 19, 2022Publication date: June 22, 2023Inventors: 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: 20230151436Abstract: Various embodiments are directed to applications (e.g., classification of biological samples) of the analysis of the count, the fragmentation patterns, and size of cell-free nucleic acids, e.g., plasma DNA and serum DNA, including nucleic acids from pathogens, such as viruses. Embodiments of one application can determine if a subject has a particular condition. For example, a method of present disclosure can determine if a subject has cancer or a tumor, or other pathology. Embodiments of another application can be used to assess the stage of a condition, or the progression of a condition over time. For example, a method of the present disclosure may be used to determine a stage of cancer in a subject, or the progression of cancer in a subject over time (e.g., using samples obtained from a subject at different times).Type: ApplicationFiled: October 18, 2022Publication date: May 18, 2023Inventors: Yuk-Ming Dennis Lo, Rossa Wai Kwun Chiu, Kwan Chee Chan, Peiyong Jiang, Wai Kei Lam
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Publication number: 20230132951Abstract: Methods are provided to improve the positive predictive value for cancer detection using cell-free nucleic acid samples. Various embodiments are directed to applications (e.g., diagnostic applications) of the analysis of the fragmentation patterns and size of cell-free DNA, e.g., plasma DNA and serum DNA, including nucleic acids from pathogens, including viruses. Embodiments of one application can determine if a subject has a particular condition. For example, a method of present disclosure can determine if a subject has cancer or a tumor, or other pathology. Embodiments of another application can be used to assess the stage of a condition, or the progression of a condition over time. For example, a method of the present disclosure may be used to determine a stage of cancer in a subject, or the progression of cancer in a subject over time (e.g., using samples obtained from a subject at different times).Type: ApplicationFiled: August 9, 2022Publication date: May 4, 2023Inventors: Eugeni Namsaraev, Yuk-Ming Dennis Lo, Rossa Wai Kwun Chiu, Kwan Chee Chan, Peiyong Jiang, Kun Sun, Wai Kei Lam
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Patent number: 11615865Abstract: Factors affecting the fragmentation pattern of cell-free DNA (e.g., plasma DNA) and the applications, including those in molecular diagnostics, of the analysis of cell-free DNA fragmentation patterns are described. Various applications can use a property of a fragmentation pattern to determine a proportional contribution of a particular tissue type, to determine a genotype of a particular tissue type (e.g., fetal tissue in a maternal sample or tumor tissue in a sample from a cancer patient), and/or to identify preferred ending positions for a particular tissue type, which may then be used to determine a proportional contribution of a particular tissue type.Type: GrantFiled: September 10, 2019Date of Patent: March 28, 2023Assignee: 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: 11605445Abstract: Factors affecting the fragmentation pattern of cell-free DNA (e.g., plasma DNA) and the applications, including those in molecular diagnostics, of the analysis of cell-free DNA fragmentation patterns are described. Various applications can use a property of a fragmentation pattern to determine a proportional contribution of a particular tissue type, to determine a genotype of a particular tissue type (e.g., fetal tissue in a maternal sample or tumor tissue in a sample from a cancer patient), and/or to identify preferred ending positions for a particular tissue type, which may then be used to determine a proportional contribution of a particular tissue type.Type: GrantFiled: September 10, 2019Date of Patent: March 14, 2023Assignee: The Chinese University of Hong KongInventors: Yuk-Ming Dennis Lo, Rossa Wai Kwun Chiu, Kwan Chee Chan, Peiyong Jiang