Adam Phillippy
@aphillippy.bsky.social
5K followers 340 following 220 posts
Finished a human genome, working on a few more 👨‍💻 Lab: https://genomeinformatics.github.io Posts are my own
Posts Media Videos Starter Packs
Reposted by Adam Phillippy
biorxivpreprint.bsky.social
A telomere-to-telomere map of somatic mutation burden and functional impact in cancer https://www.biorxiv.org/content/10.1101/2025.10.10.681725v1
aphillippy.bsky.social
The pangenome resources and genome assembly/inference approaches we are building will eventually enable complete, personalized “T2T” genomes for everyone. This is the thesis of the Q100 project (www.biorxiv.org/content/10.1...) and what my group is currently working towards. Stay tuned... [10/10]
A complete diploid human genome benchmark for personalized genomics
Human genome resequencing typically involves mapping reads to a reference genome to call variants; however, this approach suffers from both technical and reference biases, leaving many duplicated and ...
www.biorxiv.org
aphillippy.bsky.social
Each genome is unique and should be treated as such. Analyzing the complete, personalized genome of an individual (yes, with the help of AI) will reduce reference bias and allow for the deep characterization of rare and novel structural variants that are the basis of many genetic diseases [9/10]
aphillippy.bsky.social
“I am suggesting we should flip that model, and we should map the metadata to the sequence of the patient, meaning we complete the patient’s genome, and then we take all of that metadata and we annotate it onto the personalized reference.” [8/10]
aphillippy.bsky.social
By sampling the pangenome to build good priors on what a typical genome looks like, you can do a much better job of inferring a patient’s genome “Perhaps, in the future, scientists can depart from the approach of mapping sequencing reads ... and accessing data in the context of the reference” [7/10]
aphillippy.bsky.social
And there is A LOT more structural variation in a typical human genome than most people realize, even between the two haplotypes of a single person’s genome, that can have big effects but are rarely captured, e.g. recurrent inversions doi.org/10.1016/j.ce... [6/10]
aphillippy.bsky.social
This point is often lost. One enormous benefit of the Human Pangenome Project is that it improves our general understanding of natural human variation. It’s like the 1000 Genomes Project, but inclusive of ALL variation, not just the variants you can see with short-read variant calling [5/10]
aphillippy.bsky.social
When [Phillippy] hears scientists say: “Oh, the pangenome is not for me,” he tells them, “You’re using it.” Illumina’s DRAGEN software already calls variants using graph genomes. Approaches related to graph genomes are, he says, “happening behind the scenes.” [4/10]
aphillippy.bsky.social
“Conceptually, the pangenome represents all of humankind’s genetic information ... Population projects cannot sample each individual in the world, so the idea is to represent the population’s multitude.” This cannot be done with singular references, enter the HPRC @humanpangenome.bsky.social [3/10]
aphillippy.bsky.social
Vivien is always fun to chat with and I was in a slightly opinionated mood from the start -- “The idea of a single reference genome is outdated,” says NIH researcher Adam Phillippy [2/10]
aphillippy.bsky.social
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]
Reposted by Adam Phillippy
christyschnitz.bsky.social
Now Hiring! Whitney Laboratory Assistant/Associate Professor in Marine Bioscience
Apply & More Info - explore.jobs.ufl.edu/en-us/job/53...
We seek a creative, collaborative scientist whose research harnesses or advances cutting-edge tools. Please help spread the word & reach out with any questions!
Reposted by Adam Phillippy
stephenturner.us
Big news! We're hiring lots of new faculty here at the University of Virginia School of Data Science @uvadatascience.bsky.social! You can find all our postings here: datascience.virginia.edu/faculty-jobs
Reposted by Adam Phillippy
guilbourque.bsky.social
🚨 New paper alert on telomeres! 🚨
Something different from the group! Thanks to Yuxin, a talented student in the lab, we used long-reads in 75 human trios to study telomeres and their inheritance.
aphillippy.bsky.social
Someone contacted me after CHM13 came out claiming that our assembly must be contaminated by Fetal Bovine Serum because they found cow DNA in it ... I had to break it to them that it was their cow sequences that were contaminated with human. DB contamination is an insidious problem. T2T genomes help
aphillippy.bsky.social
Looks good, thanks! I missed this one, probably due to the synonym confusion (have also seen it called MER22). Tagging @leogdlima.bsky.social
aphillippy.bsky.social
We have many more exciting studies planned or on pause. Please let us get back to science-ing soon! 🙏 [fin]
aphillippy.bsky.social
Having a complete, personalized reference genome of the sample you are analyzing allows for investigations like this in the most complex regions of the genome without having to worry about reference bias. More “matched” T2T assemblies are on the way for commonly used iPSC lines like KOLF2.1J...
aphillippy.bsky.social
Fiber-seq was able to reconstruct patterns of nucleosome and protamine organization in sperm chromatin fibers! Comparing HG002 sperm cells to the reference revealed that sperm preferentially retain their CENP-A mono-nucleosomes, providing a mechanism for the transmission of paternal centromeres...
aphillippy.bsky.social
Last but not least: “Protamine lacunae preserve the paternal chromatin landscape in sperm” a project led by the Stergachis and Lesch labs that I was tangentially involved in that makes use of our recently released HG002 “Q100” reference...
www.biorxiv.org/content/10.1...
Protamine lacunae preserve the paternal chromatin landscape in sperm
The transmission of the paternal genome requires extensive chromatin reorganization, in which nucleosomes are largely replaced by protamines that drive extreme condensation of the genome in the sperm ...
www.biorxiv.org
aphillippy.bsky.social
If that’s not enough, we threw in a complete, T2T giraffe genome! Giraffe genomes are pretty cool. Almost all of their chromosomes are Robertsonian fusions of the typically telocentric ruminant chromosomes. 🐄 vs. 🦒...
aphillippy.bsky.social
Funny story, though, we found this gene in NCBI databases, but it was annotated in Streptococcus pneumoniae! This is surely human contamination in a bacterial strep sample that was not properly filtered. Lesson: use CHM13, or better yet a pangenome, when filtering for human contamination...