iiinova — where your digital self keeps evolving

Adam Phillippy @aphillippy.bsky.social · 24/08/2026

On our last day, the lab ran a pop-up coffee shop for our NHGRI colleagues, staffed by our own highly experienced baristas Suhani and Serge. Farewell NIH! Thanks for being a great home for the past 11 years 🥲 Watch for our next pop-up at Hopkins once we get properly equipped 😁

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Adam Phillippy @aphillippy.bsky.social · 13/08/2026

"Filling the holes in whole genomes: A vision for personalized genomics from telomere to telomere" Brief commentary from me, @khmiga.bsky.social, @msikic.bsky.social, Yu Kang and Yafei Mao for the T2T special issue. Why do we need complete genomes? Check it out! www.cell.com/cell/fulltex...

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Adam Phillippy @aphillippy.bsky.social · 06/08/2026

Fenn's genome: www.cell.com/cell-genomic...

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Adam Phillippy @aphillippy.bsky.social · 06/08/2026

🦒 Fun fact: this is the actual giraffe sequenced! His name is Fenn and he lives at the Cincinnati Zoo. Photo credit: Lisa Hubbard. More Fenn info: cincinnatizoo.org/happy-world-...

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Adam Phillippy @aphillippy.bsky.social · 06/08/2026

Big thanks to the T2T and GIAB teams for making the Q100 project a success! A special thanks to Nancy Hansen and Justin Zook for helping to lead this project, as well as the 1KGP, PGP, and HPRC donors for openly releasing their genomic information to everyone's benefit [13/15]

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Adam Phillippy @aphillippy.bsky.social · 06/08/2026

Even between the two haplotypes of HG002 we see significant variation, including a megabase-scale inversion of the beta-defensin locus and multiple genes present in one haplotype but not the other, such as DUSP22, CFHR1, CFHR3, GSTT1, and GSTM1 [9/15]

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Adam Phillippy @aphillippy.bsky.social · 06/08/2026

To break through this ceiling, we teamed up with Genome in a Bottle to create a new “genome benchmark” that represents the actual complete, diploid genome of HG002 [5/15]

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Adam Phillippy @aphillippy.bsky.social · 06/08/2026

🎯 Goodhart’s law: if you make a list of variants the target, people will get really good at calling those variants. But those variants are not a genome! As a result, we’ve been stuck trying to read genomes under the lamppost of short reads [4/15]

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Adam Phillippy @aphillippy.bsky.social · 06/08/2026

For the past 30 years, “whole-genome sequencing” has been a misnomer. Today the T2T Consortium publishes a dozen papers heralding a future of truly complete genomes for humans and nearly any vertebrate 👨‍🔬🐒🐦🐀🦒🐎🫏🐹🐟 (sorry, no salamanders): www.cell.com/consortium/t... 🧵[1/15]

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Adam Phillippy @aphillippy.bsky.social · 08/06/2026

T2T assemblies for nearly all major Y chromosome haplogroups courtesy of a collab between @humanpangenome.bsky.social and HGSVC! What was once the hardest human chromosome to finish can now be routinely assembled thanks to ONT + Verkko www.biorxiv.org/content/10.6...

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Adam Phillippy @aphillippy.bsky.social · 02/06/2026

Old friend and new @jhucompsci.bsky.social colleague @benlangmead.bsky.social visited the NIH today and presented a great talk on pangenomes and BWT at exactly the level I need to hear it 🚣 🚣 🚣 😆 Thank you Ben!

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Adam Phillippy @aphillippy.bsky.social · 02/04/2026

Reference mule "Symphony" pictured here with her mom, courtesy of Doug Antczak & Camille Holmes @ Cornell VetMed. I always love when we get to see pictures of the animal we sequenced, especially when they are cute 🐴🐴

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Adam Phillippy @aphillippy.bsky.social · 30/03/2026

We also identified rare structural variation on the short arms resulting in duplicated (~9%) and deleted (~3%) distal junction sequences. The DJ has been hypothesized to play a role in nucleolar function, so it will be interesting to further investigate the effects of such variation [7/8]

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Adam Phillippy @aphillippy.bsky.social · 30/03/2026

We used this insight to detect potential ROBs in large-scale sequencing cohorts (including UKBioBank) and identified candidate ROB carriers at a frequency of 0.11–0.12%, roughly matching the expected frequency of 1 per 800 individuals [6/8]

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Adam Phillippy @aphillippy.bsky.social · 30/03/2026

Thus, the most common ROBs (i.e. 13;14 or 14;21) result in the loss of exactly 2 of 10 DJ copies, making them an effective marker that can be copy-number typed via short-read sequencing! An individual with 8 DJ copies very likely carries a ROB [5/8]

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Adam Phillippy @aphillippy.bsky.social · 30/03/2026

Total rDNA copy number is highly variable and cannot be used as a reliable maker for ROBs. However, T2T human genomes have revealed that the palindromic “distal junction” (DJ) sequence immediately upstream of the rDNA is both highly conserved and typically single-copy per chromosome [4/8]

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Adam Phillippy @aphillippy.bsky.social · 30/03/2026

With the Gerton and Garrison labs, we recently discovered that most ROBs fuse at a segmental duplication located between the rDNA array and the centromere, resulting in the loss of 2 of the 10 rDNA arrays from the (diploid) genome [3/8] 📄 www.nature.com/articles/s41...

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Adam Phillippy @aphillippy.bsky.social · 30/03/2026

Robertsonian chromosomes (ROBs) are a fusion between the short arms of two acrocentric chromosomes. ROB carriers are generally healthy, but face an increased risk of miscarriage, children with trisomies, and (maybe) certain types of cancer [2/8]

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Adam Phillippy @aphillippy.bsky.social · 23/03/2026

TTT is compatible with Verkko assembly outputs, and has allowed us to investigate some interesting tangles that were previously hidden by gaps in the assembly, such as these megabase-scale arrays of PAK3-like genes on the zebrafinch Z chromosome 🐦 Try it out for yourself! (4/4)

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Adam Phillippy @aphillippy.bsky.social · 02/02/2026

The unique properties of the acrocentrics allow the genes on them to rapidly amplify and recombine, perhaps enabling accelerated evolution, which the CDS tree for GGT appears to show for gorilla [14/21]

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Adam Phillippy @aphillippy.bsky.social · 02/02/2026

We focused on two specific genes, a gorilla-specific fusion gene IGSF3-GGT and FRG1. These two genes are lovely examples of birth-and-death evolution. Intron trees show the IGSF3-GGT fusion was born ~9 Mya, while the initial FRG1 duplication dates to the ancestor of all apes ~26 Mya [12/21]

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Adam Phillippy @aphillippy.bsky.social · 02/02/2026

(4) Gorillas have 7 pairs of acrocentrics, but only 2 contain rDNA arrays. We discovered that the other 5 gorilla acrocentrics contain amplified *protein coding genes*, some of which show evidence of positive selection! [11/21]

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Adam Phillippy @aphillippy.bsky.social · 02/02/2026

(3) In some cases, non-allelic recombination can maintain >99% sequence identity between *different* acrocentric chromosomes. We first saw this in human and named them “pseudo-homolog regions” (PHRs). We can now see that PHRs are a recurring feature of all the great ape acrocentrics [9/21]

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Adam Phillippy @aphillippy.bsky.social · 02/02/2026

(2) There is a huge amount of sequence turnover on the short arms, with all major ape lineages exhibiting strikingly different satellite patterns. Even chimp and bonobo (just 1–2 My diverged) have different characteristics (e.g. bonobo has a lot more HSat1) [7/21]

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Adam Phillippy @aphillippy.bsky.social · 02/02/2026

Assuming parsimony, there has been at least one acrocentric-to-metacentric conversion on each major branch of the great apes. The human Chr2 fusion is famous, but that is the only fusion in the great ape tree. Instead, short arm inversions have been the primary driver of karyotypic change [5/21]

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Adam Phillippy @aphillippy.bsky.social · 02/02/2026

Basic intro: acrocentric chromosomes are the ones with asymmetric arms, with the centromere positioned more towards the tip (Greek άκρο) than the middle. In human, the short arms of these chromosomes are home to the 45S rDNA arrays and a whole mess of other repeats [2/21]

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Adam Phillippy @aphillippy.bsky.social · 02/02/2026

Time for a thread on our Christmas preprint “Origin and evolution of acrocentric chromosomes in human and great apes”. I had so much fun with this project and paper. It will be hard to summarize in a thread, but I’ll try www.biorxiv.org/content/10.6... [1/21]

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Adam Phillippy @aphillippy.bsky.social · 29/01/2026

Tandem repeats appear as rectangles in self-identity heatmaps. AniAnn’s literally “finds the rectangles” using edge detection and classifies them against a database of known repeat classes. Uses modimizers and matrix banding for speed. Try it out on your favorite T2T genome! Feedback appreciated!

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Adam Phillippy @aphillippy.bsky.social · 29/01/2026

New tool from @alexsweeten.bsky.social to find and classify all your satellites: "AniAnn's: alignment-free annotation of tandem repeat arrays using fast average nucleotide identity estimates" 📄 www.biorxiv.org/content/10.6... 📦 github.com/marbl/anianns

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Adam Phillippy @aphillippy.bsky.social · 10/10/2025

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. 🦒...

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Adam Phillippy @aphillippy.bsky.social · 24/09/2025

How Robertsonian chromosomes can lead to miscarriage or trisomy explained in one great figure from Human Molecular Genetics (Strachan and Read) that I have referred to many times

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Adam Phillippy @aphillippy.bsky.social · 23/09/2025

More from HG002: This figure shows the incredible progress of de novo assembly over the past 5 years. Ash1 was a good "collapsed haplotype" assembly from 2020. Now we have single-tech solutions (ONT 6B4) that can produce nearly perfect diploid assemblies out of the (HERRO/Verkko) box 🤯

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Adam Phillippy @aphillippy.bsky.social · 22/09/2025

Assembling and annotating the diploid HG002 genome from “T2T” allowed us to fill in those missing regions and explore the limitations of reference-based variant calling and benchmarking, especially within complex, segmentally duplicated regions of the genome that are often heterozygous [3/14]

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Adam Phillippy @aphillippy.bsky.social · 22/09/2025

Building benchmarks is hard, unglamorous work, but the impact can be huge. Think about how much the GIAB variant benchmarks have shaped the field over the past ~10 years. But did you know these benchmarks omit ~15% of the genome? (And not just in the centromeres...) [2/14]

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Adam Phillippy @aphillippy.bsky.social · 05/09/2025

Definitely hard to measure, but here is our best attempt from a new benchmarking paper to be preprinted in the next few weeks. Element appears to be the current king of homopolymers. Illumina does worse than HiFi beyond 20 bp. (This is all measured on human DNA)

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Adam Phillippy @aphillippy.bsky.social · 17/06/2025

As just one example, Verkko2 allowed us to assemble the first T2T Robertsonian chromosomes and pinpoint a particular SST1 satellite repeat array as the fusion site of most ROBs: www.biorxiv.org/content/10.1...

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Adam Phillippy @aphillippy.bsky.social · 17/06/2025

Congrats to @dantipov.bsky.social et al. on the publication of Verkko2! The team put a ton of work into this making it the first assembler that deals with the complexity of human acrocentric chromosomes. Lots of interesting discoveries to come! genome.cshlp.org/content/earl...

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Adam Phillippy @aphillippy.bsky.social · 15/05/2025

I remember chatting with @sergek.bsky.social and intentionally calling this a "golden threshold" so that it would be a brainworm. Glad our strategy worked and you still remember it 12 years later 😁 This was the original figure from doi.org/10.1186/gb-2...

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Adam Phillippy @aphillippy.bsky.social · 09/04/2025

A project five years in the making, we've now published complete "T2T" genomes for six additional ape species! It turns out that finishing (and analyzing) six genomes is slightly more work than one... doi.org/10.1038/s415...

A phylogeny of the 7 ape genomes that have now been completed from "T2T", with Homer Simpson representing mankind.

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Adam Phillippy @aphillippy.bsky.social · 27/01/2025

Congrats to Bryce Kille on absolutely smashing his PhD defense at Rice today with advisor @treangen.bsky.social ! Collaborating with Bryce over the past few years has been an absolute delight 👏🎉👏🎉

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Adam Phillippy @aphillippy.bsky.social · 09/01/2025

Why was @sexchrlab.bsky.social in snowy Bethesda today? Big news coming later this month! Stay tuned… 🧬

A group of NHRGI scientists having coffee together in a cafe

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Adam Phillippy @aphillippy.bsky.social · 17/12/2024

I pulled a bunch of old TIGR faculty photos from Wayback Machine for Claire's retirement symposium. Everyone had a formal headshot except you 😄

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Adam Phillippy @aphillippy.bsky.social · 14/11/2024

Reuniting sci twitter in person with a bearded @blekhman.bsky.social visiting NHGRI today! (and, yes, we both poked Julie to join bsky next)

Selfie of Adam Phillippy, Ran Blekhman, and Julie Segre standing in front of a G-gnome poster at NHGRI.

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Adam Phillippy @aphillippy.bsky.social · 08/10/2024

Such an honor to speak at Claire Fraser’s retirement symposium today and reflect on how much she shaped my own career. Wonderful to see so many old friends in the same place. What an incredible legacy ❤️🐅 #TIGR

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Adam Phillippy @aphillippy.bsky.social · 27/09/2024

"The formation and propagation of human Robertsonian chromosomes" ROBs are the most common translocation in humans, approx. ~1 per 800 people. Last year we proposed a simple mechanism for ROB formation; This year we prove it by finishing some T2T! New preprint: www.biorxiv.org/content/10.1...

Schematic of Robertsonian chromosome formation

FISH image and schematic of a complete Robertsonian chromosome

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Adam Phillippy @aphillippy.bsky.social · 16/09/2024

"Epigenetic control and inheritance of rDNA arrays" New preprint from the T2T acrocentrics team! We find a tight link between methylation and transcription of the rDNAs, including the occasional silencing of entire arrays www.biorxiv.org/content/10.1...

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Adam Phillippy @aphillippy.bsky.social · 05/09/2024

T2T-F2F 2024 is a wrap! Great to hear about the new discoveries being enabled by complete genomes, and to meet so many new, enthusiastic T2T’ers. Thanks for the great meeting @khmiga.bsky.social @ucscgenomics.bsky.social !! 🎉

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Adam Phillippy @aphillippy.bsky.social · 04/09/2024

Kicking off day 2 of #T2T-F2F in one of my favorite places (redwoods of Santa Cruz) with one of my favorite people (Jen Gerton) presenting our work sequencing Robertsonian chromosomes 🧬

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Adam Phillippy @aphillippy.bsky.social · 01/08/2024

Complete genomes for the apes! We have added bonobo, chimp, gorilla 🦍, orangutan 🦧, and gibbon to the T2T family! Lots of very cool stories buried in these genomes, some of which we have explored here, but I expect many more studies to follow: www.biorxiv.org/content/10.1...

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