Massgenomics

My short review on best practices for variant calling in clinical sequencing is online (and open access) @GenomeMedicine, just in time for #ASHG20: genomemedicine.biomedcentral.com/articles/10.11…

Great sessions on the last day, too. AI in genetics, beyond the exome for NDDs, and more.

@michaelhoffman A lot of people have stayed!

Big crowd for a Sunday-morning #ASHG23 session!

PY: T1 MRI of study participants provides 1,324 brain imaging phenotypes. GWAS yielded 1044 associations (56 novel), gene burden test yielded 148 associations, *(145 novel) #ASHG23

Now: Peng Yang from Takeda (Japan) who will share data from 10,000 Japanese genomes. He led off by pointing out the representation gap in genetic research, which tends to focus on European ancestry individuals #ASHG23

Just bumped into my old friend @dgmacarthur. It reminds me why coming to these meetings in person is so worthwhile. #ASHG23

@sadlersull Will do!

DK tidbit: variants previously known as P/LP involved in 40% of diagnoses. In 4.3%, they "rescue" variants not otherwise prioritized (e.g. noncoding, higher MAF) #ASHG23

TIL that the developers of STR detection tools really make the most of naming possibilities... I knew of LobSTR and HipSTR, and now learning about PrancSTR #ASHG23

Tony Mander from Invitae discussing the opportunities of their massive dataset, ~4.5m patients sequenced, of which ~2.5m had accompanying clinical information. A great opportunity for machine learning #ASHG23

Admittedly, they got 3 billion fragments [versus the usual ~50 million] on a handful of samples using "mostly natural sequencing by synthesis" (Ultima Genomicx), a platform unfamililar to me. #ASHG23

The talk by H. Zhao on clinical utility of deep RNA-seq in Mendelian disorder diagnostics, while not really about clinical utility, did suggest that very high depth (3 bn fragments) captures 50% more low-level or tissue-specific genes. #ASHG23

@michaelhoffman @girlscientist Agreed, the session titles are killing it at #ASHG23

@girlscientist They have really outdone themselves on some of the titles this year. #ASHG23

@StephanieEfthy1 @BCM_MSTP @bcmgenetics Agreed. Difference maker being "work steadfastly on genes that seem likely to be disease-associated" was my favorite lesson #ASHG23

Great talk from @BCM_MSTP @bcmgenetics and lessons about medium-hanging fruit in Mendelian gene discoveries #ASHG23

PB: International collaboration identified 14 patients with LOF variants, not only survivable but all patients had milder disease than classic CdL. There are some LOF variants in gnomAD in SMC3 (despite pLI=1), but these have low-skewed VAF suggesting mosaicism #ASHG23

PB: Properties Medium-hanging fruit discoveries in Mendelian disorders: Rare conditions Generic or hard to recognize phenotypes Reduced penetrance Variable expressivity Not Mendelian Unique allelic architecture #ASHG23

Now up in Rare Disease Diagnostics: Philip Boone (MGH), Heterozygous LOF variants in SMC3: Lessons from medium-hanging fruit era of Mendelian disease gene discovery. #ASHG23

DK now talking about CVA: Virtual single lab across england stores full case info, HPO terms, automated algorithms, variant classifications, evidence logs, and outcomes across all the labs in UK. #ASHG23

DK (great initials): Their pipeline uses some DRAGEN tools, some in-house tools, standard prioritization, and Exomiser. 1 in 3 patients get a diagnosis (confirms this overall Dx rate with huge #'s) #ASHG23

First up: Dalia Kasperaviciute: Interpretaion of whole genome sequencing for clinical care in rare disease on a national scale: the UK experience... they have done 60k WGS for 30k RD referrals through NHS. Wow. #ASHG23

@rdhernand I am here! Hope to see you around somewhere buddy!

Good morning #ASHG23! Are you still here? Or have you moved on to one of the other places??