Genetics person at @Illumina. Previously @BBS_Harvard, @broadinstitute, Patch Bio, and @NCSSM. he/him. Black lives still matter.

Joined February 2014
42 Photos and videos
Jacob Ulirsch, PhD retweeted
I’m delighted to finally share work from my PhD with @dalygene and @s_mccarroll. We show how human genetics and AlphaFold3-predicted protein structure can be combined to discover new mechanisms underlying missense risk in brain disorders. 1/n biorxiv.org/content/10.1101/…
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Jacob Ulirsch, PhD retweeted
Our team has a position in the SF bay area for a top computational experimental scientist for perturb-seq. illumina.wd1.myworkdayjobs.c…

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Jacob Ulirsch, PhD retweeted
Me using Claude Opus 4.8 to rename a file

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Jacob Ulirsch, PhD retweeted
dudes in SF will be 30 and be like "yeah i'm raising a seed round" bro go raise a family
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Jacob Ulirsch, PhD retweeted
Replying to @CalebLareau
@CalebLareau is doing some of the most compelling work on viral contributions to human disease. Here showing herpesvirus reactivation in Alzheimer’s disease. x.com/CalebLareau/status/205…

A history of viral encephalitis is one of the strongest risk factors for developing dementia. With @JacobJacobog02, Yifan Chen, @RNA_Life, and @RyanDhindsa, we refine this link by describing a neuronal cell type that can reactivate HSV-1 in humans 1/n biorxiv.org/content/10.64898…
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Jacob Ulirsch, PhD retweeted
We’re unwrapping a new method today @MSKCancerCenter! Led by @SydneyBlattman, @NabihMaslah, @AustinAVarela, Ronan Chaligne and @dana_peer, plus colleagues at @10xGenomics, we’re delighted to share Genotyping In Fixed Transcriptomes (GIFT): biorxiv.org/content/10.64898… 1/n

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Jacob Ulirsch, PhD retweeted
As someone who has covered cancer drug development for 25 years, one of the few things I am sure of is that the odds of technology folks thinking they understand biology are much higher than the odds they actually do.
This is totally out of control: There’s 0 - I repeat 0 - evidence any of the LLM work did anything meaningful for Rosie’s cancer I’m sorry to rain on the parade here. I know we want to believe. But, it’s possible to do a lot of things and have nothing happen @paul_conyngham co-administered α-PD-1 (conventional immunotherapy) with a TKI and the mRNA. It’s probably the most effective cancer immunotherapy of all time. This isn’t a small detail! There’s no evidence his process (beyond FDA approved doggie α-PD-1) had any impact on disease progression. The most parsimonious explanation is a partial response to α-PD-1 I get it. The chat bots make for a great story (although checking multiple LLMs isn’t validation), but it’s really just a neat story. It’s fundraising copy. Before he starts selling the “custom neoantigen mRNA vax” story to consumers, he should provide some evidence it did anything! That’s responsible citizen science This is just storytelling for the AGI true believers. Specifically, a story in search of venture money
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Jacob Ulirsch, PhD retweeted
Pinpointing the exact noncoding variants behind disease associations is challenging. Using MPRA, @LaylaSiraj, @julirsch, @ReillyLikesIt, @r_tewhey et al tested >220K variants in 5 cell types, resolving >13K & revealing mechanisms behind many disease traits broad.io/MPRA-news
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Jacob Ulirsch, PhD retweeted
⚠️ If you’re reading this, you’ve been infected* ⚠️ *~95% the human population has been infected by the Epstein-Barr Virus (EBV). Today in @Nature with @nyeo_sherry, @EMC22381830, @RyanDhindsa @SlavePetrovski, we shed some light on what happens next. nature.com/articles/s41586-0…
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Jacob Ulirsch, PhD retweeted
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Ever wondered how to choose weights for rare variant burden/SKAT tests? @jschwart37 and I did too! Check out our (@illumina) straightforward new approach that improves discovery by ~50% or more than STAAR, Regenie, and DeepRVAT!
Let’s talk about rare variant association tests - we have a new method that helps you discover more with the same data! It’s called FlexRV to signal our approach: Flexibly modeling rare variant pathogenicity improves gene discovery for complex traits. biorxiv.org/content/10.1101/…
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Jacob Ulirsch, PhD retweeted
I am a strong believer that depth of data can be just as powerful as scale of data. Deep analysis of small groups of humans, and even individuals, can lead to novel biological insights and principles. Today I am the guinea pig. In my own blood, @CalebLareau finds strong evidence that a synonymous genetic variant (no amino acid change in the protein) can impact T cell function via altered codon syntax. pnas.org/doi/10.1073/pnas.25…
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Excited to share my first contribution here at Illumina! We developed PromoterAI, a deep neural network that accurately identifies non-coding promoter variants that disrupt gene expression.🧵 (1/)
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Jacob Ulirsch, PhD retweeted
We're thrilled to introduce PromoterAI — a tool for accurately identifying promoter variants that impact gene expression. 🧵 (1/)
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Jacob Ulirsch, PhD retweeted
Though the coarse tree topologies may appear similar between versions, the relative placement of cells (color bar) in the two trees is ~random! We therefore disagree that ReDeeM is “robust and reliable” between versions as edge variants in -1 remains a large driving signal. 5/n
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Jacob Ulirsch, PhD retweeted
28 Aug 2024
In addition to the technical points raised by @CalebLareau, several biological questions remain after this preprint. We would appreciate your thoughts as these were not addressed @chenweng1991, @jswlab, @bloodgenes. 1/n
Thank you @chenweng1991, @jswlab, @bloodgenes for the feedback on our work. @LeifLudwig and I agree that the “-2” filtering method that mitigates edge bias is a critical development for ReDeeM. Nevertheless, we stand by our original preprint, noting the following: 1/n
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Jacob Ulirsch, PhD retweeted
Tools that predict the causal genes in GWAS loci are too complex! Many use XGBoost models with >45 features (i.e. L2G, Ei). CALDERA achieves better performance despite using LASSO regression and only 12 features. This makes it much easier to understand why a gene was chosen.
Simplifying causal gene identification in GWAS loci medrxiv.org/cgi/content/shor… #medRxiv
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Jacob Ulirsch, PhD retweeted
California
6 Aug 2024
What are you convinced people are pretending to enjoy?
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Any white hats out there want to make a virus that gets famous scientists to tweet about my recent papers? Unrelated, I just got a new MacBook for cheap ask me how.
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Jacob Ulirsch, PhD retweeted
Hello Berlin students, we are looking for a motivated student assistant to support our research team at @berlinnovation and @BIMSB_MDC: karriere.charite.de/stellena…. Please apply by July 20! What we do: bihealth.org/en/research/res… and mdc-berlin.de/ludwig Retweets welcome 🙂
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