Better tools for Genomics: SNOP purified oligos.
To a certain extent, the genomic research is not dissimilar from cooking: you can cook only with the ingredient you have. If you want a great dish, you better start with great ingredients.
You can read our paper "Simultaneous and stoichiometric purification of hundreds of oligonucleotides" in Nature Communications.
The genomic research relies on the availability of oligos, which are short synthetic nucleic acids sequences used as primers and probes.
Nowadays, chemically synthesized oligos are economical, yet still riddled with errors. To give an example, an oligo long 70 nucleotides is synthesized with a purity ranging from 50% to 70%. The remaining 30-50% consists of synthesis failures, which are oligos affected by severe truncations, deletions, and insertions. These synthesis failures lead to lack of specificity and affect the overall performance of probes and primers - which is particularly detrimental for those applications, e.g. targeted sequencing, where hundreds or thousands of oligo species are used simultaneously.
Synthesis failures can be removed through a purification step, but purification methods have not caught up with the synthesis capabilities. Indeed, purification is usually labor-intensive, expensive and lacks either high-throughput or yield. Consider the commonly used HPLC and PAGE purification: they can deal with one oligo at a time and cost roughly $50 per oligo – which often is greater than the synthesis cost. When we started designing panels of hundreds of probes for targeted sequencing, the purification cost of such panels became an expensive burden. Hence, we start thinking “there should be a better way to purify these oligos, saving money and time”.
So we invented SNOP: Stoichiometrically Normalizing Oligonucleotide Purification. A purification technology that is easy to use, and affordable. Rather than individually purifying each and every oligo, SNOP purifies them all simultaneously. SNOP cleverly assigns a short barcode to every oligo of a pool. The barcodes contain information about purity and the final abundance (stoichiometry) of a particular oligo within the final pool. After synthesis, the oligos are pooled together and purified by “capture probes” that recognize and read the barcodes.
SNOP purified oligos have a purity higher and more uniform than those obtained by other purification methods.
If you want to learn more about SNOP, check out our paper: https://www.nature.com/articles/s41467-018-04870-w