THE J. DAVID GLADSTONE INSTITUTES, A TESTAMENTARY TRUST ESTABLISHED UNDER THE WI (20240336965). SENSITIVE MULTIMODAL PROFILING OF NATIVE DNA BY TRANSPOSASE-MEDIATED SINGLE-MOLECULE SEQUENCING simplified abstract

SENSITIVE MULTIMODAL PROFILING OF NATIVE DNA BY TRANSPOSASE-MEDIATED SINGLE-MOLECULE SEQUENCING

Organization Name

THE J. DAVID GLADSTONE INSTITUTES, A TESTAMENTARY TRUST ESTABLISHED UNDER THE WI

Inventor(s)

Vijay Ramani of San Francisco CA (US)

Ke Wu of Martinez CA (US)

Hani Goodarzi of San Francisco CA (US)

Arjun Scott Nanda of Palo Alto CA (US)

Sivakanthan Kasinathan of Menlo Park CA (US)

SENSITIVE MULTIMODAL PROFILING OF NATIVE DNA BY TRANSPOSASE-MEDIATED SINGLE-MOLECULE SEQUENCING - A simplified explanation of the abstract

This abstract first appeared for US patent application 20240336965 titled 'SENSITIVE MULTIMODAL PROFILING OF NATIVE DNA BY TRANSPOSASE-MEDIATED SINGLE-MOLECULE SEQUENCING

Simplified Explanation

The patent application describes methods for tagmentation in single-molecule sequencing that require significantly less input compared to current protocols. Two methods, smrt-tag and samosa-tag, are introduced for detecting genetic variation, CpG methylation, and chromatin accessibility.

Key Features and Innovation

• Implementation of tagmentation for single-molecule sequencing with 90-99% less input.
• Introduction of smrt-tag for genetic variation and CpG methylation detection.
• Introduction of samosa-tag using exogenous adenine methylation for probing chromatin accessibility.
• Resolution of single-fiber chromatin structure, CTCF binding, and DNA methylation in patient-derived prostate cancer xenografts.
• Uncovering metastasis-associated global epigenome disorganization.

Potential Applications

The technology can be used in genomics research, epigenetics studies, cancer research, and understanding chromatin structure and function.

Problems Solved

• Reduced input requirements for single-molecule sequencing.
• Enhanced detection of genetic variation, CpG methylation, and chromatin accessibility.
• Improved resolution of chromatin structure and epigenetic changes in cancer.

Benefits

• Cost-effective sequencing with minimal input.
• Comprehensive analysis of genetic and epigenetic features.
• Better understanding of chromatin structure and its role in disease progression.

Commercial Applications

Potential commercial applications include offering sequencing services to research institutions, pharmaceutical companies, and biotechnology firms. The technology can also be used in diagnostic applications for cancer and other diseases.

Questions about Tagmentation

How does tagmentation in single-molecule sequencing differ from traditional sequencing methods?

Tagmentation combines tagging and fragmentation of DNA in a single step, reducing the input required for sequencing and enabling more efficient detection of genetic and epigenetic features.

What are the advantages of using samosa-tag for probing chromatin accessibility?

Samosa-tag introduces exogenous adenine methylation to add a third channel for studying chromatin accessibility, providing insights into chromatin structure and function in various biological contexts.

Original Abstract Submitted

methods are provided that implement tagmentation for single-molecule sequencing use 90-99% less input than current protocols: smrt-tag, which allows detection of genetic variation and cpg methylation, and samosa-tag, which uses exogenous adenine methylation to add a third channel for probing chromatin accessibility. samosa-tag of 30,000-50,000 nuclei resolved single-fiber chromatin structure, ctcf binding, and dna methylation in patient-derived prostate cancer xenografts and uncovered metastasis-associated global epigenome disorganization.