Long-read Sequencing of Human Immunoglobulin Gene Introns to Define a Biomarker for in Vivo Dna Break Repair

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This invention provides a method called SWIBRID for analyzing DNA break repair efficiency in humans and animals by sequencing the 'switch-joints' in the immunoglobulin heavy chain (IGH) gene of B-cells using long-read sequencing. By examining the patterns and characteristics of these naturally occurring DNA repair events, the method can detect deficiencies in DNA repair mechanisms. This information can predict the risk of developing cancer, immunodeficiencies (like CVID), or neurodevelopmental diseases, inform prognosis, and guide personalized treatment decisions. The invention includes a computer program to process sequencing data and identify repair deficiencies using features and machine learning, as well as a diagnostic kit for practical use.

Use CasesContent extracted from patent full text and abstract with AI.

• Early detection of cancer susceptibility in individuals by profiling their DNA repair efficiency.
• Diagnosis and monitoring of immunodeficiencies such as common variable immunodeficiency (CVID).
• Detection and prognosis of neurodevelopmental disorders related to DNA repair deficiencies, such as ataxia telangiectasia.
• Guiding personalized cancer therapies by determining a patient’s DNA repair status (e.g., selecting patients likely to benefit from specific chemotherapy or radiotherapy regimens).
• Screening for risk of adverse reactions to genome editing or DNA-damaging treatments based on an individual’s DNA repair profile.
• Large-scale population screening for DNA repair-related disease risks using blood or lymphatic samples.
• Pharmaceutical research and drug development targeting DNA repair pathways by providing in vivo functional readouts.
• Development of companion diagnostics for targeting therapies, such as PARP inhibitors in BRCA-deficient cancers.

BenefitsContent extracted from patent full text and abstract with AI.

• Enables functional, in vivo assessment of DNA break repair capacity, rather than relying solely on genetic mutations, thus capturing unknown deficiencies and complex mechanisms.
• Allows early detection of disease risk, enabling preventative measures or enhanced monitoring before symptoms arise.
• Supports precision medicine by enabling tailored treatments based on individual DNA repair profiles, reducing ineffective therapy and adverse effects.
• Can help distinguish between different genetic and functional causes of similar clinical presentations (e.g., differentiating CVID from allergies or recurrent infections).
• Non-invasive (blood-based) and applicable to various species, useful for both human medicine and animal research.
• Reduces diagnostic delay for difficult-to-categorize disorders like CVID or DNA repair-deficiency cancers.
• Supports high-throughput and multiplexed sample analysis due to barcoding and modern sequencing platforms, making the method scalable and cost-efficient.
• Integrates machine learning for robust classification and prediction, improving diagnostic accuracy and speed.

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Patent Abstract

The present invention relates to a method for analyzing the DNA break repair machinery of a subject, in particular, for determining at least one deficiency in the DNA break repair machinery, and, on this basis, for predicting the DNA break repair efficiency of the subject. While the analysis is performed in B-cells and comprises analyzing switch-joints of the immunoglobulin heavy chain locus (!GH) of said B-cells, the results can generally be used to predict the risk to develop a cancer, an immunodeficiency such as common variable immunodeficiency (CVID) or a neurodevelopmental disease such as ataxia telangiectasia (AT), for determining the prognosis of a cancer, or for selecting a method of treating a cancer. The invention also relates to a computer program product comprising instructions which, when the program is executed by a computer, cause the computer to carry out specific steps of the analysis, and to a kit comprising said computer program product. The method of the invention is also designated Switch-joint Breakpoint Repertoire Identification (SWIBRID).