Sequencing Generations – What’s in a Name?


Every so often someone will ask about the various “generations” of DNA sequencing or a company will claim to have the latest generation – 3rd, 4th, even “last”. (Hey, Genia, if you don’t come out with something soon, I’m going to start calling your platform “late” generation sequencing – as in “late to the party” or perhaps late as in dead.) A while back I answered a question about this on Quora (which was basically that the concept of “generations” hasn’t been used consistently and isn’t that useful).



I came up with a number of attributes that could be used to lump the various platforms into categories:

1) sequencing-by-synthesis vs direct sequencing (vs ligation vs hybridization)

2) stepped vs continuous sequencing

3) optical vs non-optical detection

4) short vs long reads

5) single molecule vs amplified


And here’s how I mapped the major platforms to these categories:

Sequencing PlatformAttributes
Illumina, BGISBS, stepped, optical, short read, amplified
Ion TorrentSBS, continuous, non-optical, short read, amplified
Pacific BiosciencesSBS, continuous, optical, long read, single molecule
Oxford Nanoporedirect, continuous, non-optical, long read, single molecule
Helicos/SeqLLSBS, stepped, optical, short read, single molecule
454SBS, continuous, optical, short*, amplified (* considered ‘long reads’ at the time, but now at least 1-2 orders of magnitude shorter than the long read technologies)
SOLiD/Complete Genomicsligation, stepped, optical, short read, amplified

I tend to just lump these all into “next generation sequencing” or, more commonly these days, just plain “sequencing” since Sanger has become such a minor component of the sequencing marketplace. If you need/want to call out something specific about a sequencing platform (e.g., single molecule or non-optical), it’s better to cite the specific thing you’re interested in rather than giving it a vague and easily misinterpreted name like “3rdgeneration” or “4thgeneration”.


For some additional comments you can check out this thread on the really useful SEQanswers forum. And for an annoyingly good counterpoint, you should read Keith Robison’s answer on Quora. He’s worth a follow on Quora for his prolific answers and you should definitely be checking out his blog over at OmicsOmics.

(Thanks to Brian Krueger for suggesting the addition of Complete Genomics!)

Shawn Baker

View posts by Shawn Baker
Founder and principal consultant at SanDiegOmics
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