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https://www.biostars.org/p/73100/

http://www.cureffi.org/2013/02/01/the-decoy-genome/

The decoy genome is an improved human genome from the regular reference. It's faster for mapping and it reduces false positive rate.

In this case, there shouldn't be any reason to use the regular human reference, because the decoy genome is simply better and faster. For instance, it has DNA sequence for common virus genomes presented in humans. It has everything in the regular reference.

Q: What's the point of the regular human reference (e.g. hg38) if the decoy version is more accurate and is a better representation for the human variation.

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To clarify, when you say "decoy genome" you hopefully mean the decoy genome and the reference genome together; the decoy genome itself is not a complete reference, but a collection of contigs assembled from reads that didn't map to the current reference genome, but are known to be human sequence.

The decoy genome certainly seems to be a useful supplementary data set for speeding up read mapping to the human genome but it cannot be better than the reference because it is not comparable to the reference.

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  • $\begingroup$ But you just said it has everything in the regular reference? And it has sequences not in the regular version too. Shouldn't it be just better? $\endgroup$
    – SmallChess
    Commented Mar 13, 2017 at 6:59
  • $\begingroup$ The decoy genome does not have everything in the reference. It is separate from the reference; it only contains sequence that couldn't be mapped to the current version of the reference. From your second link: "an entire ‘decoy genome’ to capture reads from human exome or whole genome sequencing that fail to align to the human reference genome." $\endgroup$
    – twrightsman
    Commented Mar 13, 2017 at 7:01
  • $\begingroup$ Quote: "If you’re just starting alignment now, you can use hs37d5.fa.gz, which is all of human genome b37 plus the decoy" in the second link. I think the decoy version does have everything in the regular reference. $\endgroup$
    – SmallChess
    Commented Mar 13, 2017 at 7:04
  • $\begingroup$ No, hs37d5.fa.gz has the "human genome b37 plus the decoy". The b37 reference genome and the decoy genome are separate sequences, but they are combined in that gzipped FASTA file. $\endgroup$
    – twrightsman
    Commented Mar 13, 2017 at 7:08

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