Efficient base determination in sequencing reactions
A technology for sequencing and sequencing, applied in 1/026,337, 61/061 submitted on March 13, 6 fields submitted on March 12, 2008, which can solve the problems of sequencing efficiency limitation, limited signal-to-noise ratio, unsuitability, etc.
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Embodiment 1
[0364] Embodiment 1: prepare DNBs
[0365] The following is an exemplary protocol for making DNBs (also referred to herein as "replicons") from nucleic acid templates of the invention comprising a target nucleic acid interspersed with one or more adapters. First, the single-stranded linear nucleic acid template is amplified with a phosphorylated 5' primer and a biotinylated 3' primer to obtain a biotin-labeled double-stranded linear nucleic acid template.
[0366] First, resuspend MagPrep-Streptavidin magnetic beads (Novagen Part. Prepare streptavidin magnetic beads in nuclease-free water). Place the centrifuge tubes in a magnetic centrifuge tube rack, allow the magnetic particles to settle, remove the supernatant and discard. The beads were then washed twice in 800 µl 1x Bead Binding Buffer and resuspended in 80 µl 1x Bead Binding Buffer. The amplified nucleic acid template from the PCR reaction was brought up to a volume of 60 μl, and 20 μl of 4x magnetic bead binding b...
Embodiment 2
[0372] Example 2: Single and dual c-PAL
[0373] Fully degenerate second anchor probes of different lengths were tested in a dual anchor probe detection system. The combination used was: 1) Standard one-of-a-kind anchor ligation using an anchor molecule and a 9-mer sequencing probe, wherein the anchor molecule binds the adapter adjacent to the target nucleic acid from 4 positions from the adapter. 2) use the same first anchor molecule and a double anchor molecule ligation comprising a degenerate 5-mer second anchor molecule and a 9-mer sequencing probe, starting at 9 sites from the adapter 3) using the same first anchor molecule and a second anchor molecule comprising a degenerate 6-mer and a double-anchor ligation of a 9-mer sequencing probe, starting at 10 sites from the adapter start the assay; and 4) use the same first anchor molecule and a double anchor molecule ligation comprising a degenerate 8-mer second anchor molecule and a 9-mer sequencing probe from 12 sites fro...
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