Danny Miller, MD, PhD

In honor of ASHG week (since I won’t be there), see "Choose your human genome reference wisely", in which Vivien Marx interviewed me @fergalmartin.bsky.social @lh3lh3.bsky.social @danrdanny.bsky.social @heidirehm.bsky.social and others on the state of the human reference rdcu.be/eJejg 🧵[1/10]

@fkma.bsky.social

Thank you Dr. Danny Miller @danrdanny.bsky.social for hosting, and fantastic job Dr. Mastrorosa @fkma.bsky.social!
@uwgenome.bsky.social

brotmanbaty.org/news/long-re...

Literal case in point: we worked with @danrdanny.bsky.social (and transfusion medicine teams across two organizations) to use long-read WGS to solve the case of an untransfusable patient.

#hemesky #medsky

doi.org/10.1111/trf....

One never knows the power and persuasion of elementary school teachers. Jonas ("Gus") Gustafson's fifth grade instructor 'allowed me to establish a life-long knack and passion for STEM.’
@uwmedicine.bsky.social
@danrdanny.bsky.social
brotmanbaty.org/news/promisi...

GitHub - jgust1/needLR: A structural variant filtering and prioritization tool for long-read sequencing data A structural variant filtering and prioritization tool for long-read sequencing data - jgust1/needLR

Interested in SV calling from LRS data but overwhelmed by the 25,000 variants you're sorting through? Check out needLR! Gus just updated it today to include SV calls from 450 1000 Genomes samples (900 haplotypes), vcf output, and much more. github.com/jgust1/needLR

Has anyone had luck submitting a paper without submitting all author names on the paper? I am tired of spending an hour or more adding people to a journal submission site just to have the paper editorially rejected the next day... I know some journals have forms you can upload, but some do not.

The first 100 were R9, then we started generating data on both R9 and R10. ~150 total samples are R9, and the rest are R10. Should be about 380 samples online right now, and 500 up by the end of the month.

I am very sad to share that Scott Hawley passed away this morning. Scott was my graduate advisor and no other person had such a positive impact on my life. I will miss him dearly.

Such a beautiful place but so many contrasts that I will be processing for a long time. Did anything happen while I was gone? 🫠

I never knew what it meant to go on a life changing trip until now. I just spent an amazing week in Nairobi teaching genetics to some truly wonderful physicians and seeing kids with suspected genetic conditions. It felt all the more special to have been there on Martin Luther King Jr. Day.

Really good questions. Used blat/blast to annotate. We do not see variation in the VNTR as it's the same size in all affected individuals and their parents. We don't have a way to check in the controls but I assume it is the same size. We did not look at methylation in the SVAE.

A Diagnostic Blind Spot: Deep intronic SVA_E Insertion identified as the most Common Pathogenic Variant Associated with Canavan Disease Canavan disease (CD) is a neurodegenerative disorder caused by biallelic disease-causing variants in the ASPA gene. Here, we utilized long-read sequencing (LRS) to investigate eight individuals clinic...

A homozygous SVA retrotransposon insertion is discovered to be likely the most common mutation in ASPA (encodes aspartoacylase) underlying Canavan disease. 1/

Gonzalez, Bell, et al. medRxiv
www.medrxiv.org/content/10.1...

We were able to easily see the insertion using using LRS. And while you can see it with SRS (split reads, target site dup), it was not detected by prior clinical or research efforts. Another argument for why LRS will be used as a first test in the inpatient and outpatient setting in the near future.

The amazing thing? Based on analysis of ~80,000 individuals the allele frequency of this insertion would make it the most common pathogenic variant associated with this devastating condition--more common than known pathogenic SNVs or indels.

A Diagnostic Blind Spot: Deep intronic SVA_E Insertion identified as the most Common Pathogenic Variant Associated with Canavan Disease Canavan disease (CD) is a neurodegenerative disorder caused by biallelic disease-causing variants in the ASPA gene. Here, we utilized long-read sequencing (LRS) to investigate eight individuals clinic...

Been looking forward to sharing this for a long time! Great collaboration with folks from across the world in which we identified a SVA_E insertion missed by standard clinical testing in individuals with Canavan disease, an early onset neurodegenerative disease.

www.medrxiv.org/content/10.1...

Fine, this job isn’t all that terrible…

Added!

Day 4 and 5 of computational genomics at CSH: students giving their project pitches and the view from my grant writing nest.

YouTube video by Coldplay Coldplay - ALL MY LOVE (Official Video) (Directors' Cut)

Your feel-good video for today. Dick Van Dyke at 99. www.youtube.com/watch?v=o4Ol...

Day 2 of Computational Genomics at Cold Spring Harbor during the intro to UNIX session. 24 great students, 5 amazing TAs, fantastic lectures, and a few instructors who mostly complain about the coffee.

Biology of Genomes Cold Spring Harbor Laboratory Meetings & Courses -- a private, non-profit institution with research programs in cancer, neuroscience, plant biology, genomics, bioinformatics.

Biology of Genomes 2025 is coming up:
- meeting dates: May 6 - 10, 2025
- abstract deadline: Feb 14, 2025
We hope to see you there for another great meeting with a fantastic speaker lineup!

meetings.cshl.edu/meetings.asp...

Covers of Science and Nature journals in the past 2 weeks denoting remarkable progress of life science with A.I. tools

A vertical takeoff of life science with #AI LLLMs.
Publication of 10 new foundation models of Proteins, DNA, RNA, methylation, cells, and interactions, evolution, and design in the past couple of weeks!
Unprecedented progress, reviewed in the new Ground Truths
erictopol.substack.com/p/learning-t...

Amazing story

Excellent suggestion--except I can't take part in it. I was fortunate to receive a DP5, which was key to getting a job, having a fast start to my lab, etc. But it excludes me from the early career reviewer program. I am not sure what the reasoning is for this limitation.

Good read about how the NIH functions. After 2 years as a new investigator I only now feel like I am starting to understand the process. This is one of the challenges for new investigators: why is the learning curve so steep?

Added!

Show me a worse fortune for an early career researcher…

Added you!

done!

I love the starter packs, but adding people is a giant pain in the ass. Is there an easier way to add someone beyond editing it through your profile?