
Whole Exome Sequencing May Skip Large Segments of DNA - bookofjoe
https://academic.oup.com/clinchem/article/66/1/199/5610509
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LifeIsBio
“Clinical Exome Studies Have Inconsistent Coverage” seems like a significantly
better title. The current HN one doesn’t make sense.

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epistasis
Precisely, if it's not skipping large segments of the genome it's not exome
sequencing, that's the entire reason that we do exomes instead of WGS.

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Gatsky
Weird this is here... this is a well known result, such studies have been
coming out for at least 5 years.

The value proposition for whole exomes is diminishing as sequencing itself
gets cheaper ie might as well do a whole genome. Exomes are still useful in
some situations, eg cancer or formalin fixed tissue.

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rotexo
Whole genomes bring their own complications. You will have tons of variants of
unknown significance in each patient. Then you would want functional data to
see if there is an impact on transcription/translation of the protein, and the
tissue of interest might not be accessible for such an analysis. There is some
interesting stuff on the horizon—like humanizing homologous genes in C.
elegans and CRISPRing in the mutation of interest, then doing functional
studies in the worm. Not perfect, but it could give you functional information
in a clinically relevant time frame.

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rotexo
Worth noting that the sequencing for this analysis was performed from
2012-2016. 4 years is a long time in the NGS world, and it is highly likely
there have been chemistry improvements since then. Though it wouldn’t surprise
me if inconsistency in coverage in clinical whole exomes remains.

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RocketSyntax
Probably at start of first exon and end of last exon. Or regulatory regions
before them.

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RocketSyntax
edit title to say "segments of genes"

