RECOMBINANT POLYMERASES FOR INCORPORATION OF PROTEIN SHIELD NUCLEOTIDE ANALOGS

    公开(公告)号:US20240271203A1

    公开(公告)日:2024-08-15

    申请号:US18544190

    申请日:2023-12-18

    IPC分类号: C12Q1/6869 C12N9/12 C12Q1/686

    摘要: Provided are compositions comprising recombinant DNA polymerases that include amino acid substitutions, insertions, deletions, and/or exogenous features that confer modified properties upon the polymerase for enhanced single molecule sequencing or nucleic acid amplification. Such properties include enhanced performance with large nucleotide analogs, increased stability, increased readlength, and improved detection of modified bases, and can also include resistance to photodamage, enhanced metal ion coordination, reduced exonuclease activity, reduced reaction rates at one or more steps of the polymerase kinetic cycle, decreased branching fraction, altered cofactor selectivity, increased yield, increased accuracy, altered speed, increased cosolvent resistance, and the like. Also provided are nucleic acids which encode the polymerases with the aforementioned phenotypes, as well as methods of using such polymerases to make a DNA or to sequence a DNA template.

    Multiprocessor pipeline architecture

    公开(公告)号:US11983790B2

    公开(公告)日:2024-05-14

    申请号:US15147835

    申请日:2016-05-05

    摘要: Exemplary embodiments for a multiprocessor pipeline architecture that converts signals from sequencing sample acquisition into sequence data, comprising: a custom coprocessor card configured to directly receive a stream of serialized sensor data generated by an image sensor, wherein the sensor data represents frame-by-frame intensity values for pixels comprising the image sensor, wherein the image sensor captures images of light emitted from a plurality of reaction cells of a removable integrated sequencing chip; a first coprocessor that continually receives the stream of serialized sensor data and transposes the frame-by-frame intensity values into reaction cell chunks, each of the reaction cell chunks representing movie data of the pixel intensity values of a corresponding reaction cell across the frames over a predetermined time window; a buffer that repeatedly receives the reaction cell chunks and stores in contiguous memory locations the reaction cell chunks for each respective reaction cell over a larger predetermined time window to create larger reaction cell chunks; and a plurality of second coprocessors that retrieve the larger reaction cell chunks from the buffer and convert, in parallel, the pixel intensity values into base-by-base sequence data even as additional reaction cell chunks are received by the buffer, such that the second coprocessors begin raw base calling before all the sensor data for the sequencing sample acquisition is obtained. Aspects of the invention include methods for base calling using single instruction multiple data vector processing units.

    Recombinant polymerases for incorporation of protein shield nucleotide analogs

    公开(公告)号:US11891659B2

    公开(公告)日:2024-02-06

    申请号:US17523670

    申请日:2021-11-10

    IPC分类号: C12N9/12 C12Q1/6869 C12Q1/686

    摘要: Provided are compositions comprising recombinant DNA polymerases that include amino acid substitutions, insertions, deletions, and/or exogenous features that confer modified properties upon the polymerase for enhanced single molecule sequencing or nucleic acid amplification. Such properties include enhanced performance with large nucleotide analogs, increased stability, increased readlength, and improved detection of modified bases, and can also include resistance to photodamage, enhanced metal ion coordination, reduced exonuclease activity, reduced reaction rates at one or more steps of the polymerase kinetic cycle, decreased branching fraction, altered cofactor selectivity, increased yield, increased accuracy, altered speed, increased cosolvent resistance, and the like. Also provided are nucleic acids which encode the polymerases with the aforementioned phenotypes, as well as methods of using such polymerases to make a DNA or to sequence a DNA template.

    NUCLEIC ACID SEQUENCING METHODS AND SYSTEMS
    10.
    发明公开

    公开(公告)号:US20240035082A1

    公开(公告)日:2024-02-01

    申请号:US18045687

    申请日:2022-10-11

    IPC分类号: C12Q1/6869

    CPC分类号: C12Q1/6869

    摘要: The present disclosure provides compositions, methods and systems for sequencing a template nucleic acid using a polymerase based, nucleic acid binding reaction involving examination of the interaction between a polymerase and template nucleic acid in the presence of one or more unlabeled nucleotides. The methods rely, in part, on identifying a base of a template nucleic acid during nucleic acid synthesis by controlling the sequencing reaction conditions. Template nucleic acid bases may be identified during an examination step followed by an optional incorporation step.