Adam Phillippy
@aphillippy.bsky.social
5K followers 340 following 210 posts
Finished a human genome, working on a few more 👨‍💻 Lab: https://genomeinformatics.github.io Posts are my own
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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...
aphillippy.bsky.social
While annotating these new rDNAs, Nagaraja noticed an open reading frame in the IGS that was absent from prior references. It turns out this ORF codes for a small protein that appears unregulated in weird cellular states like senescence or HEK293 cells. Unclear if it has any phenotypic impact...
aphillippy.bsky.social
“Analysis of a Novel Human Protein, ORF3, Encoded by Spacer rDNA” is more rDNA fun spawning from a prior collaboration with the Schlessinger and Larionov labs in which we completed an updated rDNA reference sequence (GenBank KY962518.1)...
link.springer.com/article/10.1...
Analysis of a Novel Human Protein, ORF3, Encoded by Spacer rDNA - Journal of Molecular Evolution
An open reading frame in the intergenic spacer of human ribosomal (r)DNA codes for a 190 amino acid, 22 kDa protein that we have named ORF3. It comprises a 5’AluSx repeat sequence encoding 96 amino acids followed by a stretch of 94 amino acids containing a unique repeated stretch of 5 hydrophobic residues. Full copies of ORF3 have been isolated as transformation-associated recombination clones from mouse:human hybrid cell lines containing human chromosomes 21 or 22. In initial instances where the chromosome complement of rDNA repeats is fully resolved in whole genomes, in CHM13 cells, complete copies of ORF3 are mainly concentrated in a tandem cluster on chromosome 21, while other chromosomes contain 1 or 2 full copies, with the sequence in other rDNA repeats interrupted by a frameshift mutation. A diploid cell complement (HG002) again has both complete open reading frames (ORFs) and other copies with the frameshift or deletions. In searches among non-human primate sequences to assess the evolutionary history of ORF3, a > 93% conserved copy of the full sequence of the ORF, as well as copies with in-frame deletions, was found in bonobo, but only fragments homologous to the ORF were seen in chimpanzee, orangutan, and gorilla rDNA examined thus far. ORF3 was expressed as a V5-tagged chimeric protein in human kidney epithelial HEK293 cells, and both ORF3-V5 and endogenous ORF3 were detected with a newly generated antibody. The protein is found in both cytoplasm and nucleus. However, upon treatment of cells with RNase A, the protein is excluded from the nucleus, suggesting that it is in complexes with RNA. Although any function is currently unknown, the ORF3 protein is upregulated, speculatively associated with changes in chromatin, in viral-transformed HEK293 cells and in human diploid fibroblast cells rendered senescent by treatment with etoposide, ionizing radiation, or an oxidant (H2O2).
link.springer.com
aphillippy.bsky.social
This one started by noticing the chr22 rDNA array in CHM13 was inactive and hypermethylated. Tamara did some great follow-up experiments to find: silent rDNA arrays associate less with nucleoli and other rDNAs, removing methylation re-activates them, and their activity status appears heritable...
aphillippy.bsky.social
Last week we were in the Washington Post for our characterization of Robertsonian chromosomes. This week we are entering our 10th day of being shut down and all of our research is on hold. To help me feel not-so-bad, here is a thread of some studies we released right before the shutdown 🧵 [1/n]...
Reposted by Adam Phillippy
jmschreiber91.bsky.social
Now that I'm settled in at @umasschan.bsky.social, I'm hiring at all levels: grad students, post-docs, and software engineers/bioinformaticians!

The goal of my lab is to understand the regulatory role of every nucleotide in our genomes and how this changes across every cell in our bodies.
Reposted by Adam Phillippy
robp.bsky.social
And it's posted! If you're interested and eligible, please consider applying through the UMD portal: umd.wd1.myworkdayjobs.com/en-US/UMCP/j....

If you're a PI working in algorithmic genomics (& you can recommend my lab to your top graduating students ;P), please let them know!
aphillippy.bsky.social
Yes, some embryos should be unaffected or balanced ROB carriers. The page I pulled that original image from lists some rates at the bottom for Downs: mymds.bham.ac.uk/genetics/rob...
aphillippy.bsky.social
Thanks, Harmit! My group still talks about your NHGRI seminar from a few years back. Many minds were blown that day. Changed the way we think!
aphillippy.bsky.social
Human Chr2 was probably the result of a telomeric fusion of two (sub)metacentrics, rather than a Robertsonian fusion of two acrocentrics, but either way the explanation for how it could fix so quickly is probably meiotic drive. Summons @harmitmalik.bsky.social to correct me if I'm wrong