Methods and systems for analyzing nucleic acid molecules
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Publication Number
US-12312634-B2
Publication Date
2025-05-27
Expiration Date
Abstract
The disclosure provides methods for processing nucleic acid populations containing different forms (e.g., RNA and DNA, single-stranded or double-stranded) and/or extents of modification (e.g., cytosine methylation, association with proteins). These methods accommodate multiple forms and/or modifications of nucleic acid in a sample, such that sequence information can be obtained for multiple forms. The methods also preserve the identity of multiple forms or modified states through processing and analysis, such that analysis of sequence can be combined with epigenetic analysis.
Core Innovation
The invention relates to monitoring residual disease or recurrence of disease in a subject where the disease is cancer, using cell-free DNA (cfDNA). A sample comprising at least 10 ng cfDNA is provided and split into first and second aliquots, and the cfDNA from each aliquot is separately assayed to obtain sequence data with different information content.
For the first aliquot, cfDNA is assayed to obtain sequence data irrespective of methylation state, and the sequence data is analyzed for SNVs, indels and/or gene fusions. For the second aliquot, cfDNA is assayed to obtain sequence data comprising information on the methylation state of the cfDNA.
Nucleic acids derived from the first and/or second aliquot are subjected to target capture so that molecules having target sequences are captured for subsequent analysis. The sequence data from both aliquots is then analyzed together to monitor residual disease or recurrence of disease.
Claims Coverage
One independent claim is provided. It comprises a cfDNA-splitting workflow that generates methylation-independent variant sequence data and methylation-state-associated sequence data, with target capture and joint analysis to monitor residual disease or recurrence; the claim framework includes three inventive features.
Dual-aliquot cfDNA sequencing for variant and methylation-state information
Splitting a sample comprising at least 10 ng cfDNA into first and second aliquots, assaying the first aliquot to obtain sequence data analysed for SNVs, indels and/or gene fusions irrespective of methylation state, and assaying the second aliquot to obtain sequence data comprising information on the methylation state of the cfDNA.
Target capture of nucleic acids from both aliquots prior to subsequent analysis
Subjecting nucleic acids derived from the first aliquot and/or the second aliquot to target capture, capturing molecules having target sequences for subsequent analysis.
Joint analysis of methylation-independent and methylation-state sequence data to monitor cancer recurrence
Analyzing the sequence data from the first and second aliquots to monitor residual disease or recurrence of disease in a subject where the disease is cancer.
The independent claim centers on monitoring residual disease or recurrence by combining sequence data from two cfDNA aliquots with different information types, after target capture, followed by integrated analysis.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Monitoring residual disease or recurrence of disease in a subject where the disease is cancer.
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