Compositions, methods and systems for processing or analyzing multi-species nucleic acid samples
Inventors
West, John • Chen, Richard • Haudenschild, Christian • Bartha, Gabor • Luo, Shujun
Assignees
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Publication Number
US-11814750-B2
Publication Date
2023-11-14
Expiration Date
Abstract
Provided herein are compositions, methods, and systems for sample processing and/or data analysis. Sample processing may include nucleic acid sample processing and subsequent sequencing. Methods and systems of the present disclosure can be used, for example, for the analysis of a nucleic acid sample from a human, non-human, and combinations thereof.
Core Innovation
The invention provides a method for detecting the presence of cancer in a subject by analyzing a biological sample that includes human nucleic acid molecules derived from the human subject and non-human nucleic acid molecules derived from one or more oncoviruses or bacteria associated with cancer. The method enriches both human and non-human nucleic-acid subsets by hybridizing the human nucleic acid molecules and the non-human nucleic acid molecules to capture probes.
The capture probes include a first plurality of probes configured to hybridize to the human nucleic acid molecules and a second plurality of probes configured to hybridize to the non-human nucleic acid molecules. After enrichment, the method sequences the enriched set of nucleic acid molecules to yield sequence information comprising sequences of human nucleic acids and sequences of non-human nucleic acids present in the biological sample from the human subject.
The disclosed approach further supports integrated analysis of the sequence information by aligning the enriched sequences to reference sequences and identifying the source of the human or non-human nucleic acids based on the aligning step. In dependent claim refinements, the human-targeting probe set is configured with sequences complementary to reference genome sequences with specified GC content and/or configured to hybridize to sequences complementary to HLA, T-cell receptors, B-cell receptors, or regions of microsatellite instability.
Claims Coverage
The independent claim is clm-00001. It includes an enrichment architecture with separate first and second capture probe pluralities for human and non-human nucleic acids, followed by sequencing that yields both human and non-human sequence information. Dependent refinements add probe configuration constraints and downstream alignment/source-identification operations.
Cancer detection by dual human and oncovirus/bacteria nucleic-acid enrichment and sequencing
Providing a biological sample with human nucleic acid molecules and non-human nucleic acid molecules derived from one or more oncoviruses or bacteria associated with cancer; enriching both subsets by hybridizing to capture probes comprising a first plurality of probes for human nucleic acids and a second plurality of probes for non-human nucleic acids; and sequencing the enriched set to yield sequence information comprising sequences of both human nucleic acids and non-human nucleic acids from the subject.
Human-targeting probe GC-content configuration
Configuring the first plurality of probes to contain sequences complementary to reference genome sequences having a GC content higher than the average in the reference sequence.
Human-targeting probe targeting of immunogenetic and microsatellite instability regions
Configuring the first plurality of probes to contain sequences complementary to HLA, T-cell receptors, B-cell receptors, or regions of microsatellite instability.
Alignment of enriched sequences to reference sequences
Aligning the sequences of the enriched set of nucleic acid molecules to a plurality of reference sequences.
Source identification based on alignment
Identifying the source of the human or non-human nucleic acids based on the aligning step.
Plasma-sample implementation
Carrying out the method using a plasma sample.
Across the independent claim and its refinements, the core coverage is a hybridization-based enrichment using separate human and non-human capture probe pluralities, followed by sequencing that yields both human and non-human sequence information. Dependent claim coverage adds specific probe configuration constraints and downstream alignment and source identification tied to the enriched sequences.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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