Jacob Kitzman

And a poster today (9259W) from talented undergrad researcher Ellie Bloss. Then, on Friday, two coding MAVEs for the price of one, from amazing postdoc Seba Vishnopolska (poster 5039F)

excited to be at #ASHG25! Lab has brought a series of functional screens - talks tomorrow from postdoc Adelaide Tovar @adel-aide.bsky.social (945am) and clinical asst prof Tony Scott (215pm) showing a pair of high-throughput functional screens.

The Department of Human Genetics at the University of Michigan is looking for a new faculty colleague at the rank of Assistant Professor. Please share!

careers.umich.edu/job_detail/2...

Delighted for this to be published at AJHG @ajhgnews.bsky.social ! Updates vs the preprint include new comparisons to AlphaMissense and other predictors. We hope this map will help improve clinical variant interpretation in MUTYH! #VUS #VariantEffects #ColorectalCancer www.cell.com/ajhg/fulltex...

Saturation mapping of MUTYH variant effects using DNA repair reporters With widespread clinical genetic testing, variants of uncertain significance are rapidly accumulating in cancer-risk genes. We used a high-throughput assay to test every missense variant in MUTYH, a k...

🚨New from @jacobkitzman.bsky.social & co!
📄Saturation mapping of MUTYH variant effects using DNA repair reporters
#MAVE

They don't care that republicans still get cancer and other diseases and fall on hard times and have special-needs kids. This was the deal. "We will hurt the people you hate even if it hurts you" and half the country signed up in blood

As a diversity grant dies, young scientists fear it will haunt their careers The Trump administration defunded the National Institute of Health's MOSAIC grant program, which launched the careers of scientists from diverse backgrounds.

A group of scholars and I had a chance to share our experiences with the MOSAIC program being terminated 🧪

www.npr.org/sections/sho...

We hope this serves as a useful resource to assist with rare variant interpretation, and believe our approach can be extended to other DNA repair factors where the #VUS burden challenges the actionability of genetic testing. 5/5

We examined individual-level clinical phenotypes of MUTYH biallelic individuals, in collaboration with a clinical lab (Ambry Genetics). Individuals with a pathogenic+missnse VUS had much higher polyposis risk -- when their VUS scored as abnormal by our assay 4/5

Our map perfectly separates known pathogenic and benign variants from ClinVar, and based upon clinical calibration, it provides ‘strong’ evidence to resolve the >1000 standing clinical missense VUS 3/5

To measure MUTYH variant function, we leveraged a reporter containing a mispair of 8oxoguanine w/ adenine, the substrate that MUTYH recognizes. AFAIK, this is the first MAVE coupled to a direct readout of repair at an DNA oxidative damage lesion. 2/5

Saturation mapping of MUTYH variant effects using DNA repair reporters Variants of uncertain significance (VUS) limit the actionability of genetic testing. A prominent example is MUTYH, a base excision repair factor associated with polyposis and colorectal cancer, which ...

New preprint! Led by postdoc Shelby Hemker, we systematically test the function of every possible coding mutation in MUTYH, a colorectal cancer risk gene with a high pathogenic carrier rate (~1:50 in some ancestry groups). #VUS #VariantInterpretation
www.biorxiv.org/content/10.1...
1/5

Senator Tina Smith said: This is the ultimate dick boss move from Musk - except he isn’t even the boss, he’s just a dick. That was in response to Musk saying “Consistent with President @realDonaldTrump's instructions, all federal employees will shortly receive an email requesting to understand what they got done last week. Failure to respond will be taken as a resignation.” Musk responded @SenTinaSmith “What did you get done last week?”

Elon, I hate to break it to you but you aren’t my boss. I answer to the people of Minnesota.

But since you bring it up, I spent last week fighting to stop tax breaks for billionaires like you, paid for by defunding health care for moms and babies

Trump Administration Stalls Scientific Research Despite Court Ruling (Gift Article) Using an arcane law, officials have effectively delayed funding from the National Institutes of Health, leaving medical studies in jeopardy.

New York Times article now up on Federal Register stuff.

www.nytimes.com/2025/02/21/s...

1/n

In short: SpliceAI and Pangolin generally performed well. Splicing effects are harder to predict in exons vs introns. Gene model annotation really matters!  We think the places where they disagree will be interesting targets for future MPSAs.  3/3

This leverages MPSAs from our group and others. Cathy led several of these, including one published this past summer in WT1, a  transcription factor where alt splicing is disrupted in Mendelian forms of nephrotic syndrome www.kireports.org/article/S246...   2/3

Last paper from the group for 2023, now out at Genome Biology! Led by recent bioinformatics grad Cathy Smith, we used #VariantEffect maps from massively parallel splicing assays (MPSA) to test bioinformatic splicing effect predictors genomebiology.biomedcentral.com/articles/10....  1/3

Finally, also on Thursday, PB1111 from talented undergrad Kirsten Nishino (also w/ Steve Parker & Adelaide Tovar) examines how environment effects modify transcriptional response using this modular MPRA system 5/5

On Sat, PB1089 from postdoc Adelaide Tovar (& Steve Parker lab) uses a modular MPRA to interrogate enhancer-promoter context and cell type influences on regulatory action 4/5

Also, PB1030 from 2xDr Anthony Scott and colleagues at Ambry Genetics shows how we've calibrated another deep mutational scan of another #LynchSyndrome gene, MLH1, for use in clinical variant interpretation 3/5

Check out these posters on Thurs too! In PB1006, we present a really cool (imho) DMS strategy from postdoc Shelby Hemker which goes beyond drug or viability selections to read out function of DNA repair factor variants 2/5

So many great talks and posters to see at #ASHG23 #ASHG2023! Here are a few from my group. Thurs 11:15AM (session 23), postdoc Seba Vishnopolska will present a deep mutational scan of a key #LynchSyndrome factor PMS2. 1/5