Heterogeneous Nucleic Acid Detection via Segmented Sequencing
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Solution Overview
Problem
The detection of foreign nucleic acids in heterogeneous biological samples is challenging due to noise from the host genome, making it difficult to distinguish and quantify nucleic acids from cancer tissue or other foreign sources, such as transplanted organs, in samples containing a mix of genomic materials.
Innovation Solution
A method involving sequencing reactions on circulating cell-free nucleic acids, using long-read sequencing technologies like SMRT, SOLiD, SOLEXA, Ion Torrent, or Genome Sequencer FLX, to directly sequence and analyze the ratios of unique sequences, allowing for the relative quantification of different genomes and adjustment of therapeutic regimens based on the presence of foreign nucleic acids.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional detection methods are used on heterogeneous nucleic acid samples, then the detection process is simpler, but the ability to distinguish and quantify foreign nucleic acids is insufficient due to host genome noise
Solution Approach 1:
The patent segments the heterogeneous nucleic acid sample into distinct populations by performing multiple separate sequencing reactions with different conditions (e.g., different primers, different enrichment strategies). Each reaction targets and amplifies specific nucleic acid populations, allowing precise quantification of foreign nucleic acids against the host background without being overwhelmed by the total complexity of the sample.
Solution Approach 2:
The patent introduces intermediary steps between sample collection and final detection, including nucleic acid extraction, enrichment, and multiple sequential sequencing reactions. These intermediary processes act as filters and amplifiers that enhance the signal from foreign nucleic acids while suppressing host genome noise, thereby improving detection precision without requiring a single overly complex detection device.
2Reliability
If the therapeutic regimen is increased based on high foreign nucleic acid quantity (>0.5%), then treatment effectiveness improves, but the risk of overtreatment and side effects increases
Solution Approach 1:
The patent implements a feedback mechanism where the detected quantity of foreign nucleic acids directly informs therapeutic regimen adjustments. By establishing quantitative thresholds (e.g., >0.5% triggers regimen increase, <1% allows reduction), the system provides objective feedback that guides clinical decisions, ensuring treatment intensity matches actual disease burden and reducing both undertreatment and overtreatment scenarios.
Solution Approach 2:
The patent changes the parameter of therapeutic regimen intensity based on the measured parameter of foreign nucleic acid quantity. By dynamically adjusting treatment parameters (dosage, frequency) in response to quantified biomarker levels, the system optimizes treatment effectiveness while minimizing unnecessary exposure to therapeutic side effects through precise parameter matching.
Data Source
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AI summary
Methods and compositions for detecting molecules in a heterogeneous sample are disclosed. The methods and compositions disclosed herein may be used for the treatment of a disease or condition characterized by the presence of nucleic acids from at least two different genomic sources. Additionally, the methods and compositions disclosed herein may be used to diagnose, predict, or monitor the status or outcome of a disease or condition characterized by the presence of nucleic acids from at least two different genomic sources. The heterogeneous samples may be from a transplant recipient, a chimeric individual, a subject suffering from a pathogenic infection, or a subject suffering from a different condition such as cancer.