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Reposted by Floris Barthel

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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Reposted by Floris Barthel

UC Santa Cruz Genomics Institute @ucscgenomics.bsky.social · 06/08/2026

We’ve sequenced a marmoset! Grad student @prajnahebbar.bsky.social & @benedictpaten.bsky.social led the effort, and expect it to enable scientists to learn more about genes that contribute to memory loss and Alzheimer's. 🔗https://news.ucsc.edu/2026/08/first-complete-marmoset-genome/

A quote from Prajna Hebbar, graduate student at UC Santa Cruz and lead author on the T2T marmoset paper, reads "Routine T2T genomics is making findings easier... It's great to be in an era where we're not stuck with the technical problems- we can go into the biology and make discoveries relevant to human health." A small monkey is pictured on the side.

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Floris Barthel @florisbarthel.bsky.social · 03/08/2026

A KaryoScope/HKS adaptation for (long and short) read RNA-seq could be an interesting project ;) @camillemrcht.bsky.social

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Reposted by Floris Barthel

Floris Barthel @florisbarthel.bsky.social · 28/07/2026

Excited to share a big KaryoScope update this past week: the HKS k-mer backend is now integrated, and you can build databases for any features of interest. The complete @humanpangenome.bsky.social HG002 assembly (~6.3 Gbp) now annotates in 21 minutes on a MacBook Pro. 🧵

Macbook laptop showing KaryoScope actively running alongside the final output karyotype plots

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Floris Barthel @florisbarthel.bsky.social · 28/07/2026

Getting KaryoScope off the cluster and onto a personal computer is a milestone we cared about. Genome analysis belongs to everyone, not just institutions and corporations that have the resources to maintain high-performance compute clusters.

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Floris Barthel @florisbarthel.bsky.social · 28/07/2026

Feature sets are not tied to a genome: any annotation that tiles a reference can become one. Here is a database we built for the Arabidopsis Col-CEN T2T reference, with chromosome, gene, region, and repeat feature sets, including the CEN180 satellite arrays.

KaryoScope annotation for the arabidopsis genome shown across four feature sets

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Floris Barthel @florisbarthel.bsky.social · 28/07/2026

Per feature set the cost is remarkably flat: 138 to 146 s of lookup each (chromosome, region, repeat, subtelomere, gene, acrocentric), plus a brief smoothing burst. Runtime scales linearly with feature sets queried. Try it yourself: gist.github.com/fpbarthel/6e9537f6c60188ba029bcbf397d2c6e9

gist.github.com

Reproduce KaryoScope v2.1 karyotyping of the T2T-HG002 v1.1 diploid assembly end to end (macOS / Apple Silicon, ~20 min at 8-10 threads, 16 GB+ RAM)

Reproduce KaryoScope v2.1 karyotyping of the T2T-HG002 v1.1 diploid assembly end to end (macOS / Apple Silicon, ~20 min at 8-10 threads, 16 GB+ RAM) - reproduce_karyoscope_hg002.sh

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Floris Barthel @florisbarthel.bsky.social · 28/07/2026

Some run statistics: peak 941% CPU across 10 threads, peak 10.2 GB RAM on an M1 Max. Broad plateaus are k-mer lookup, sharp bursts are hierarchy-aware smoothing, and each of the six feature sets appears as its own block.

CPU and RAM statistics for KaryoScope annotating the HG002 genome on a MacBook M1 laptop

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Floris Barthel @florisbarthel.bsky.social · 28/07/2026

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Reposted by Floris Barthel

bioRxiv Genomics @biorxiv-genomic.bsky.social · 22/07/2026

HPRC2: A human pangenome reference with near-complete coverage of common genetic variation www.biorxiv.org/content/10.64898/20…

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Reposted by Floris Barthel

bioRxiv Bioinfo @biorxiv-bioinfo.bsky.social · 28/05/2026

Fast Set Operations for Compact k-mer Sets www.biorxiv.org/content/10.64898/20…

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Floris Barthel @florisbarthel.bsky.social · 26/05/2026

Busy month at the lab. We've refreshed our site with four new preprints: arm-specific telomeres in astrocytoma (Jehangir), pancreatic cancer assembly (Wagner), telomere crisis in astrocytes (Mbegbu) and KaryoScope (Ranallo-Benavidez). Plus new(-ish) lab members Shea, Nick, Daniel, Griffin, and Divy.

barthel-lab.org

the barthel laboratory - studying telomere dysfunction in gliomagenesis and evolution at TGen

The Barthel Laboratory studies how telomere dysfunction drives structural genome evolution and shapes the molecular trajectory of cancer. Based at TGen in Phoenix, Arizona, we combine cytogenetics and...

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Floris Barthel @florisbarthel.bsky.social · 22/05/2026

Huge credit to co-first authors Mimi Mbegbu and Yi-An Chen, and to collaborators Pippa Cosper and Tianpeng Zhang. 📄 Preprint: www.biorxiv.org/content/10.6...

biorxiv.org

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Floris Barthel @florisbarthel.bsky.social · 22/05/2026

Together: telomere dysfunction preferentially destabilizes acrocentric chromosomes and disrupts the nucleolus they collectively build. The nucleolus emerges as a structural nexus linking telomere crisis to large-scale genome rearrangement.

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Floris Barthel @florisbarthel.bsky.social · 22/05/2026

We expected broad genomic instability. Instead, telomere crisis zeroed in on the acrocentrics, consistent with findings from Beth Sullivan's lab over a decade ago using dominant-negative TRF2. doi.org/10.1371/jour... doi.org/10.1371/jour...

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Floris Barthel @florisbarthel.bsky.social · 22/05/2026

To probe nuclear organization, we used Hi-C. Standard pipelines discard the rare inter-chromosomal contacts at acrocentric arms, so we recovered them with KaryoScope, our alignment-free tool. These contacts were persistently depleted in crisis cells. bsky.app/profile/flor...

KaryoScope Hi-C inter-chromosomal contact maps and the log2 fold-change map with the chr13 row/column in blue

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Floris Barthel @florisbarthel.bsky.social · 22/05/2026

Why acrocentrics? Their short arms carry the NORs that nucleate the nucleolus. In crisis cells, nucleoli broke down: compact spheres gave way to dispersed, necklace-like structures, with rDNA transcription and processing decoupled.

UBF/fibrillarin immunofluorescence, compact vs necklace nucleoli

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Floris Barthel @florisbarthel.bsky.social · 22/05/2026

The rearrangements were strikingly dynamic. Chromosome 13 translocations were common early but transient, replaced by new partners at later passages, while whole-chromosome losses persisted. Crisis generates a shifting, subclonal landscape of damage.

DAPI metaphase spreads with arrowheaded translocations, plus pie charts of shifting translocation composition

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Floris Barthel @florisbarthel.bsky.social · 22/05/2026

Multicolor FISH revealed subclonal abnormalities largely invisible to short-read sequencing. The bias was striking: acrocentric chromosomes carried 41% of all abnormalities despite being 15% of the autosomal genome. Chr13 was abnormal in >92% of metaphases.

chromosomal abnormality catalog organized by type (deletions / translocations / fusions) across four clones showing an abundance of acrocentric involvement

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Floris Barthel @florisbarthel.bsky.social · 22/05/2026

To capture it, we grew normal human astrocytes with HPV E6/E7 (inactivating p53 and Rb) but no telomerase, so cells divide through progressive telomere erosion. We tracked them longitudinally from senescence bypass through crisis, an otherwise inaccessible window.

the longitudinal growth curve showing the senescence and crisis growth plateaus

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Floris Barthel @florisbarthel.bsky.social · 22/05/2026

Telomere crisis is an engine of genomic instability, driving the structural evolution of cancer genomes. Our new preprint finds this damage isn't random: it converges on the nucleolus and the chromosomes that build it. 🧵 www.biorxiv.org/content/10.6...

two multicolor FISH karyograms of crisis cells

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Floris Barthel @florisbarthel.bsky.social · 18/05/2026

@timtriche.bsky.social I realize this link isn’t in the manuscript but (earlier slightly outdated version) KaryoScope outputs (annotated bed files, plots) for HPRC is available at s3-us-west-2.amazonaws.com/human-pangen... in case anyone wants to explore the output data structure

s3-us-west-2.amazonaws.com

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Floris Barthel @florisbarthel.bsky.social · 18/05/2026

We are working on it! Not striving for perfection but want it to be good enough to represent three years of hard work 💪 it should be worth the short wait! @trhyker.bsky.social

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Floris Barthel @florisbarthel.bsky.social · 18/05/2026

Should be live Monday/Tuesday-ish. Code is ready but want to create a proper landing page and organize the documentation.

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Floris Barthel @florisbarthel.bsky.social · 18/05/2026

Look forward to hearing with you think of it!

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Floris Barthel @florisbarthel.bsky.social · 17/05/2026

📄 Paper: www.biorxiv.org/content/10.6... 💻 Code*: github.com/barthel-lab/KaryoScope *currently still set to private, opening to the public early next week as we wrap up the software release In the meantime, dive into the manuscript and share your comments and feedback.

biorxiv.org

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Floris Barthel @florisbarthel.bsky.social · 17/05/2026

Annotation is the pangenome era's bottleneck, and KaryoScope is our step toward dissolving it: a framework that any annotation source can plug into. Tremendous thanks to @trhyker.bsky.social for leading this work, and to all co-authors.

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Floris Barthel @florisbarthel.bsky.social · 17/05/2026

KaryoScope analyzes sequence data faster than instruments from @pacbio.bsky.social , @nanoporetech.com, Illumina, and @elembio.bsky.social (and others) produce it, on laptop-grade hardware. Real-time, on-instrument sequence annotation is within reach.

Four-panel performance scaling of KaryoScope across CPU thread counts. Top left: feature-ID lookup throughput (Mb/s) for KMC (red) and HKS (blue) k-mer backends. Bottom left: peak memory (GB) for each backend. Top right: smoothing-step runtime (minutes) comparing Python (red) and Rust (blue) implementations. Bottom right: smoothing-step memory. HKS and Rust each scale substantially better than KMC and Python.

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Floris Barthel @florisbarthel.bsky.social · 17/05/2026

KaryoScope works on any sequence input, beyond diploid assemblies: long reads, short reads, Hi-C, RNA-seq, metagenomics. It detects SVs from individual long reads (manuscripts forthcoming) and dissects cancer genome assemblies (HG008): bsky.app/profile/florisbarthel.bsky.social/post/3mle3v75bpk2k

KaryoScope karyotype of the HG008 pancreatic tumor assembly. Each chromosome is shown as a track colored by chromosome of origin, revealing complex rearrangements: derivative chromosomes from reciprocal translocations, dicentric chromosomes, and chromoplexy-like patterns where blocks of one chromosome's sequence appear within another.

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Floris Barthel @florisbarthel.bsky.social · 17/05/2026

@khmiga.bsky.social and @glennislogsdon.bsky.social have charted centromeres. KaryoScope adds pangenome-scale variation: chr9 megabase inversion, chr3/chr5 repeat losses, FISH-validated. See also: www.science.org/doi/10.1126/... www.biorxiv.org/content/10.6...

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Floris Barthel @florisbarthel.bsky.social · 17/05/2026

FSHD1, a muscular dystrophy, is caused by structural changes in D4Z4, a complex subtelomeric repeat array on chromosomes 4q and 10q. Across hundreds of @humanpangenome.bsky.social, KaryoScope first catalogs D4Z4 diversity, including configurations previously not described.

Pangenome-scale D4Z4 macrosatellite catalog from KaryoScope. Panels A and C–F: KaryoScope tracks (satellites, genes, repeats, subtelomere, D4Z4 arrays) for representative haplotypes across chromosomes 4q and 10q, including canonical, multi-array, and mixed configurations. Waffle charts (B) show D4Z4 structural category frequencies across 249 chr4 and 333 chr10 haplotypes. Contingency tables (G) summarize diploid combinations. Scatterplot (H) compares repeat-unit counts between haplotypes within individuals.

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Floris Barthel @florisbarthel.bsky.social · 17/05/2026

Robertsonian translocations are complex chromosomal rearrangements of acrocentric chromosomes. @aphillippy.bsky.social, @thinks.lol, and Jen Gerton showed SST1 is the fusion substrate; KaryoScope confirms this from k-mers alone. See also: www.nature.com/articles/s41... www.nature.com/articles/s41...

KaryoScope annotation of three Robertsonian translocation assemblies (top: rob(14;21), middle: rob(13;14) in GM03786, bottom: rob(13;14) in GM04890). Each row shows six progressively zooming panels from full contig (~130–200 Mb) down to 200 kb at the fusion site. Tracks per panel show chromosome of origin, genes, repeats, satellites, and acrocentric features. The SST1 satellite block (green) is visible at every fusion point.

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Floris Barthel @florisbarthel.bsky.social · 17/05/2026

Built on k-mer matching (short, fixed-length DNA fragments), KaryoScope annotates a complete diploid human genome at base-pair resolution in ~2 minutes, across repeats, satellite families, genes, and chromosome-end structure. ~300× faster than RepeatMasker.

Schematic comparing FISH (fluorescence in situ hybridization) and KaryoScope workflows side by side in four parallel steps: feature definition (cloning vectors vs. genomic feature sets), fragmentation (vector processing vs. k-mer enumeration), label assignment (fluorescent probes vs. labeled k-mer sets), and query (in situ probe binding vs. k-mer database lookup). KaryoScope is presented as a computational analog of FISH.

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Floris Barthel @florisbarthel.bsky.social · 17/05/2026

The human genome's most variable and clinically important regions (centromeres, telomeres, and acrocentric short arms) have been hardest to study at scale. Thrilled to share KaryoScope, our new preprint that brings them within reach. 🧵 www.biorxiv.org/content/10.6...

KaryoScope karyotype of the HG002 diploid assembly. All 22 autosomes plus X and Y, each shown as paired haplotypes (h1, h2). Each chromosome has a full-length track colored by chromosome of origin, a centromere zoom panel showing satellite composition, and a subtelomere zoom panel. Legends map chromosomes, satellite families, and subtelomeric features to colors.

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Floris Barthel @florisbarthel.bsky.social · 08/05/2026

Huge congrats to Justin Zook, @mishakolmogorov.bsky.social, @glennislogsdon.bsky.social, Chunlin Xiao & the full team, and to @trhyker.bsky.social for driving KaryoScope. A milestone resource for somatic variant benchmarking in repetitive regions of cancer genomes.

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Floris Barthel @florisbarthel.bsky.social · 08/05/2026

KaryoScope also resolved two reciprocal translocations (chr12↔15, chr18↔X), foldback inversions, acrocentric short-arm rearrangements, and complex multi-chromosomal events; all reconciled against dGH ground truth. Check out the pre-print for a complete overview of everything we observed.

KaryoScope visualization of two reciprocal translocations

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Floris Barthel @florisbarthel.bsky.social · 08/05/2026

That α-satellite fusion produced what turned out to be a putative functional dicentric chromosome: two CDRs ~1 Mbp apart on D7Z1 and D6Z1, beautifully characterized by CenMAP from the @glennislogsdon.bsky.social lab. 🔗 github.com/logsdon-lab/...

CenMAP visualization of the 7p-6p dicentric chromosome

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Floris Barthel @florisbarthel.bsky.social · 08/05/2026

KaryoScope resolved a striking chromoplexy event linking chr 3, 6, 7, and 11 into three hybrid tumor chromosomes, and pinpointed the chr6↔chr7 breakpoint deep inside the α-satellite array of both centromeres.

Chromoplexy causing a complex series of events linking chromosomes 3, 6, 7, and 11 in three hybrid tumor chromosomes

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Floris Barthel @florisbarthel.bsky.social · 08/05/2026

Our lab contributed via KaryoScope, our k-mer-based sequence annotation tool. It produced an ISCN-annotated karyotype of the tumor assembly that was concordant with KromaTiD dGH SCREEN cytogenetics across all 35 tumor chromosomes.

Side-by-side computational and traditional multi-color karyotype for HG008T

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Floris Barthel @florisbarthel.bsky.social · 08/05/2026

🧵 Excited to contribute to a new preprint led by Justin Zook & the NIST/GIAB team: "A complete human pancreatic cancer genome": the first near-complete, haplotype-resolved tumor cell line assembly (HG008-T, hypodiploid PDAC). 📄 www.biorxiv.org/content/10.6...

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Floris Barthel @florisbarthel.bsky.social · 29/04/2026

Very excited for our lab's first paper to be printed!

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Floris Barthel @florisbarthel.bsky.social · 23/04/2026

Somatic SV breakpoints were enriched at telomeres and centromeres regardless of local telomere length, a constitutive layer of structural fragility replicated in external genomic datasets. This work was led by Maryam in the lab with a great team of collaborators at Mayo Clinic, NCI and Weizmann.

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Floris Barthel @florisbarthel.bsky.social · 23/04/2026

Our working model: short telomeres drive breakage via BFB cycles; long ALT-maintained telomeres coincide with ecDNA, potentially linked to replicative repair mechanisms.

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Floris Barthel @florisbarthel.bsky.social · 23/04/2026

New preprint! We used Oxford Nanopore long-read sequencing to ask: does chromosome-arm-specific telomere length shape how IDH-mutant astrocytoma genomes evolve? Short answer: yes, and in two opposite directions. 🔗 www.biorxiv.org/content/10.6...

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