System and process for data-driven design, synthesis, and application of molecular probes

Abstract

The disclosure provides methods and systems for designing and synthesizing probes to capture a representative sample of genomic variants of a target genome from a sample. The methods include providinga multiple sequence alignment (MSA), designing a plurality of representative subsequences, and optionally synthesizing a nucleic acid probe. The designing step can comprise designating a plurality ofintervals in the MSA, shifting start positions for each MSA subset, clustering the aligned subsequences within each adjusted subset, and determining a representative sequence for each reduced MSA subset. The disclosure also encompasses methods of isolating a plurality of nucleic acid variants of a targeted genomic subregion from a sample using the disclosed probe design, as well as the probe compositions themselves.

Description

[0001] Cross References to Related Applications [0002] This application claims the benefit of US Provisional Application No. 62 / 302,078, filed March 1, 2016, the disclosure of which is incorporated herein by reference in its entirety. technical field [0003] The present invention provides methods and systems for the rational design, synthesis and application of molecular probes. [0004] Statement Regarding Sequence Listing [0005] The Sequence Listings related to this application are provided in text format rather than paper and are incorporated into this specification by reference. The name of the text file containing the sequence listing is 57930_Sequence_Final_2017-02-28.txt. The text file is 2KB in size, was created on February 28, 2017, and is submitted together with this manual. Background technique [0006] An early means of capturing known DNA stretches was Southern blotting. Variants of this technique, including RNA-capturing Northern blotting, have been us...

AI Technical Summary

Problems solved by technology

Therefore, many gene regions of interest may be too variable for Sanger sequencing to be useful

[0012] 3. The primers preferentially bind to the gene sequence that the primer itself shows higher sequence homology, which will cause sequencing bias

While powerful, whole metagenomic sequencing by NGS is expensive and can be inefficient, especially in applications where only a few selected genetic regions and / or organisms are of interest

Images