Sequencing Methods to Watch in 2012: The Fall of the Genome




So, the question for 2012 would seem to be whether or not this will be the year that we finally see a commercial implementation or even a prototype of a nanopore-based sequencer. Source: Arizona State University

Predicting what might happen next year in the field of next-generation sequencing may seem futile on the surface. Sequencing technology advances so rapidly these days that the predictions that might seem outlandish at the start of the year will appear to have been much too conservative by year’s end. But, your editors atBioTechniques are up to the challenge, and here we have assembled our predictions and thoughts on the world of next-generation sequencing in 2012.

  1. The year of the pore? Nanopores have attracted renewed attention in recent years as many of the technical hurdles stopping their use in DNA sequencing (slowing transit though the pore, aligning bases properly for reading, actually designing the proper-sized nanopore) have been largely addressed. So, the question for 2012 would seem to be whether or not this will be the year that we finally see a commercial implementation or even a prototype of a nanopore-based sequencer. The potential of such a system is clearly enormous – rapid speed, single molecule analysis, no need for imaging, and tremendous scalability. But thus far, articles appearing in the pages of journals have only described limited sequencing of short stretches of DNA as proofs-of-concept. Going out on a limb, we predict 2012 will be the year that nanopores make their move and show some more of their true potential. Whether or not a commercial system will be announced in 2012, we suspect a prototype instrument will be revealed, setting the stage for nanopores to finally march into the light of next-generation sequencing systems.
  1. More genome sequences, but more of the same?The number of individual human genomes sequenced should rise significantly in 2012 (far eclipsing the number currently sequenced). This increase should help in our understanding of human genetic variation (both SNPs and CNVs), and provide new insights into diseases such as cancer. But the main question that will arise during 2012, as more genome sequences come to light, is whether or not this tells us more about the genetic foundations of humans disease than genome wide association studies (GWAS) have done for the past five to 10 years. Initial results point to yes, but 2012 will be an important year when it comes to using sequencing to explore the genetic roots of human disease.
  1. Data analysis dilemma. The volume of data generated using next-generation sequencing is mind boggling. Beijing Genomics Institute, now one of the major sequencing centers in the world, anticipates generating on the order of thousands of terabytes of data in 2012. Although computational advances and increases in data storage capabilities have decreased the time to assemble whole genomes, sequencer output is running far ahead of our ability to analyze and interpret the data. We suspect that 2012 should see a renewed dedication to data analysis and interpretation as large-scale sequencing centers concentrate their efforts on human genetics and clinical applications. Even with this, it is clear that the data deluge will continue in the coming years and the need for computational biologists will grow (graduate students take note).
  1. Another, yet unknown, sequencing approach rises.With next-generation sequencing now moving at seemingly breakneck speeds, and nanopores and other rapid single-molecule methods either on their way or currently available, we wondered if there might be any other sequencing approaches that will be revealed in 2012. Although unlikely, approaches that physically interact with DNA for decoding (e.g., approaches such as single-molecule sequencing using transmission electron microscopy being developed by Halcyon Molecular and ZS Genetics) could come into play next year depending on the pace of development. But more likely than a new method appearing in 2012 would be the refinement and extension of current methods toward faster and higher outputs, with platforms such as Ion Torrent beginning to show their true capacity.
While there is clearly some degree of uncertainty about what advances will take place in next-generation sequencing development next year, what is very clear is that advances will occur and the volume of sequence in databases around the globe will rise significantly yet again. If you have any comments, or would like to make your own prediction of what will happen in the world of sequencing next year, post your thoughts on our Twitter or Facebook pages, or email them directly