[yuppiepuppie]

Not sure how to feel about this. I think its super cool that you can dive into this, but it sucks that its your son that has this condition for which you have to do this analysis. I hope it all turns out well.

Quick question: where did you get your genome read and get the raw files? As far as I know, as service like 23andme does not give you back the raw files.

[packeted]

Thanks for the kind words. Actually we got the trio whole genome sequencing through our neurologist/geneticist a couple of years ago. It was performed by a company called GeneDx. They interpreted the data at the time which is how we got to a diagnosis but knowing I'd want to dive in to it later I asked for the raw data. They provided it as the raw CRAM files and also the VCF (variant call files) which are a bit smaller. But each company has its own pipeline and for example uses different versions of the reference human genome which made working with the data quite hard for me and the people I enlisted. Claude Science seemed to make very easy work of it. Also to be clear, the question I was trying to answer was whether his mutation was likely passed down through my sperm or mom's egg - neither of us have the mutation in our own genomes. Turns out spontaneous (de novo) mutations are much more common in sperm because Spermatogonial stem cells have undergone many more cell divisions over their lives. Everyone has de novo mutations (70+), one of his just happens to be in an unlucky location.

GeneDx aren't direct to consumer so you'd need to get it ordered through a physician but there are some DTC options for example, Dante Labs, Nebula Genomics, Sequencing.com but I can't speak to the quality of their testing.

23andMe doesn't do whole genome or whole exome sequencing. They use a microarray technology that tests for about 650,000 single nucleotide polymorphisms. You can actually download the your raw data on 23andMe and do your own analysis or use a tool like promethease.

I'm an MD so I'm quite comfortable exploring this data and whatever it uncovers. Tools like Claude Science are going to put a lot of power in the hands of every day people, potentially outside the guidance of genetic counseling/docs, which many organizations in the past (including the FDA) have been hesitant to allow.

[ahknight]

I can vouch for Nebula. Just follow their recommendation to not get the 1x service if you want to use the data for medical reasons. The more passes they make, the more accurate the result.

Downside: those files are HUUUUUGE. Have a good reason to do it before pulling one down and trying to work with it.

[packeted]

Files are huge for sure (mine are like 25Gb x 3 of us) but Claude Science / Macbook Pro M5 Max knocked out my analyses in minutes using command line tools like bcftools and scripting. Honestly think this opens up WGS data to much easier analysis and refreshing those analyses in minutes as new discoveries are made.