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Unfortunately, metagenomics is currently the lowest hanging fruit of genomics/biology right now. Sequencing has gotten exponentially cheaper to the point that t
by alphaoverlord 16y ago
Unfortunately, metagenomics is currently the lowest hanging fruit of genomics/biology right now. Sequencing has gotten exponentially cheaper to the point that these types of projects are feasible (the paper you cite is actually a proof of concept for their metagenomics pipeline), that everyone is just sequencing this shit out of everything. That said, there are quite a few pitfalls with this current approach:
1. Big data in biology is still lacking comparable analytical capability.
2. Most high throughput sequencing technologies (next gen sequencing) is using polymerase based technologies that have short reads. Polymerase (the basis of PCR) requires a primer to start the reaction - and the choice of primer can introduce non-trivial bias into the obtained results. Short reads are pretty good in dealing with most bacteria, but the reaction gets pretty hairy with hyperthermophiles (bacteria with regions high in GC content) and more complex eukaryotes (long stretches of repeated regions are difficult to resolve with the shotgun approach).
3. We will probably only see DNA reads that are slightly different from what we know to exist already. The generalization they make that 99% of species cannot be cultured with current methods is true - but an analogous scenario with DNA can be made. The sequencing reactions will probably be optimized for sequences with similar composition to what we already see. The task of extracting DNA from bulk material is not trivial - this can remove large swathes of species from view even if the sequencing is trivial. Complex 3D RNA and DNA structures such as hairpin loops and noncanonical pairing makes sequencing hard.
It's definitely still a difficult question to tackle, but more difficult than doing it are answering the questions "What can we learn from this?" and "What should we sequence?"
- bluekeybox 16y ago"Sequencing has gotten exponentially cheaper to the point that these types of projects are feasible (the paper you cite is actually a proof of concept for their metagenomics pipeline), that everyone is just sequencing this shit out of everything. " Well that's exactly why I'm excited, but your phrasing makes it seem as if this is just a matter of course. Game changers in many fields often arise because some previously expensive resource becomes economically more accessible (cheaper). You make it sound like "The Model T Ford is just a low-hanging fruit of cheaper gasoline." Nothing is exciting if you pull that angle. Regarding (1): Yes, and that "lack" is why I currently have a job (employed as a computer scientist helping analyze big data). If nothing was "lacking", analysis would be as easy as a biologist pushing a few buttons in a spreadsheet-like program, and nobody would need a computer scientist helping them. Regarding (2): That's only a technical issue that is the main contributor to (1) -- were it not for short reads, analytics would be much easier. Regarding (3): From some reports (can't confirm right now but can look for a citation if you're interested), I have seen exactly the opposite -- that the estimates of biological variation from metagenomic data are actually skewed towards higher diversity than expected. Could be due to errors in the pipeline, and is being worked on, but some of that variation could also be explaining legitimate biodiversity.