Tim Fennell

HTSJDK 6.0.0 is released! Major updates include: - Full support for VCF 4.0-4.5 (finally) - Full support for BCF 2.2 (including bgzf) - File->Path everywhere for NIO file system plugins - Proper CRAM/CRAI indexing - CSI index support for many formats - Non-trivial performance improvements

github.comRelease 6.0.0 · samtools/htsjdkhtsjdk 6.0.0 Release Notes Major release. It includes every change in 5.0.2. Before upgrading, read Upgrading from 5.x; to explain differences from files 5.x wrote, see Output that differs from 5...

And so many bug fixes and minor improvements. Details here: github.com/samtools/hts...

New Release Friday! Today brings: - Riker 0.5.0 with wgs per-base coverage output in bigwig format and some minor bugfixes - Methylsieve 0.3.0 with support for TAPS+ and Illumina 5-base See: github.com/fulcrumgenom... github.com/fulcrumgenom...

github.comGitHub - COMBINE-lab/gravlax: Annotation-independent molecular-evidence archives for single-cell RNA-seqAnnotation-independent molecular-evidence archives for single-cell RNA-seq - COMBINE-lab/gravlax

Thanks to friends at Broad Clinical Labs for providing access to some TAPS+ data for testing!

Tim Fennell reposted

Fulcrum Genomics

@fulcrumgenomics.com

Interested in methylation sequencing and alternative sequencing platforms? Find @nilshomer.com and @yfarjoun.bsky.social in the #ASHG2026 poster hall! UMI-aware methylation sequencing Sequence context and variant-calling accuracy Oct. 21 2:30–4:30 p.m. EDT Bring your toughest bioinformatics problem.

Tim Fennell reposted

Rob Patro

@robp.bsky.social

Got to share some recent (& ongoing) work with folks at @fulcrumgenomics.com yesterday! Instead of my normal style (go deep on 1 project), I covered 3 recent projects: github.com/COMBINE-lab/... github.com/COMBINE-lab/... github.com/zrudnick/bra... Thanks for inviting me to meet with the team!

github.comGitHub - tfenne/bz2-ng: API compatible next-generation port of libbz2 / libbzip2API compatible next-generation port of libbz2 / libbzip2 - tfenne/bz2-ng

Oh ... also ... can I interest anyone in a ~3x faster drop-in re-implementation of libbzip2: github.com/tfenne/bz2-ng

View full thread

It's around 3x faster at encode, and 3-4x faster decode on general corpora. And up to 8x faster on highly repetitive data like various tag-streams in CRAM.

It honors bzip2's memory contracts, produces identical output unless input (at block scale) is entirely repetitive (i.e. multiple valid minimal rotations), and has been subjected to dozens of CPU-hours of fuzz testing!

github.comGitHub - tfenne/bz2-ng: API compatible next-generation port of libbz2 / libbzip2API compatible next-generation port of libbz2 / libbzip2 - tfenne/bz2-ng

Oh ... also ... can I interest anyone in a ~3x faster drop-in re-implementation of libbzip2: github.com/tfenne/bz2-ng

I realize bzip2 isn't the most in-vogue compression these days, but part of that is that it's so slow. Over the space of about a week, I was able to get Claude to build a drop-in replacement that is substantially faster. Drop-in in the way zlib-ng is for zlib - no recompile, just swap the library.

github.comGitHub - fulcrumgenomics/bigwig-rs: A Rust library for reading and writing bigWig, wig and bedGraph filesA Rust library for reading and writing bigWig, wig and bedGraph files - fulcrumgenomics/bigwig-rs

Not all bioinformatics work is glamorous. I was surprised that I couldn't find a fully featured library for reading/writing bigwig files in Rust over the weekend. So now there's: github.com/fulcrumgenom...

Existing libraries both lacked complete support for the full range of bigwig internal block formats and had crazy dependency chains (ffs: I don't need async to write bigwig).

Part of the CI for bigwig-rs is generation of a broad range of files and round-tripping through both itself and every major bigwig library including IGV and igv.js!

Tim Fennell reposted

bwa-mem3 is now 6-8x faster than the original, and now as fast as minibwa. What's stopping you from using it?

Tim Fennell reposted

Fulcrum Genomics

@fulcrumgenomics.com

#ASHG26 #ASHG2026 #HumanGenetics #Genomics

I'm winding up to generate a mostly large joint callset (about 10k samples) through GATK's HaplotypeCaller to make gVCFs, and then on into GenomicsDB. I'm curious - are folks still actively using HaplotypeCaller / GATK for germline joint genotyping? Or are folks moving on to something else?

github.comGitHub - fulcrumgenomics/chelae: Fast, highly accurate, read-trimming for NGS data.Fast, highly accurate, read-trimming for NGS data. - fulcrumgenomics/chelae

New release of chelae over the weekend. The fastest adapter and qual trimming software you've probably never heard of 😉 Still measures the fastest of the bunch, though AdapterRemoval v3 isn't too far behind. Now with support for streaming interleaved FASTQ! 🧬 🖥️ github.com/fulcrumgenom...

github.comRelease v2.17.2 · DerrickWood/kraken2Minor release to fix bugs with k2 wrapper, speeds up merging using multi-threading. We have another release pending that will see significant speed ups to classification. What's Changed Multi-data...

Do you use kraken2? If so, don't skip the new release yesterday, now available on bioconda: github.com/DerrickWood/... Includes a PR from me that speeds up both database load (up to 3X) and classification (24-39% improvement)!

And if you use it for the off-label purpose of filtering out reads from not-your-organism, also check out k2tools for faster fastq filtering: github.com/fulcrumgenom...

Tim Fennell reposted

github.comRelease v0.12.0 · fg-labs/bwa-mem30.12.0 — faster on both architectures, a faster --meth, and a large safety pass A broad optimization release that speeds up both Arm and x86 (unlike 0.11.0, which concentrated on Arm), plus a methy...

14 Sept

bwa-mem3 v0.12.0 is out 🧬 Since v0.10.0: faster on both Arm & x86 (--fast is now ~2× minibwa and stock is within ~15% on x86) while staying a byte-identical (--compat). It also brings ~30–40% faster methylation and a big memory-safety pass. github.com/fg-labs/bwa-... #bioinformatics #genomics

@ashlandpoetrypress.bsky.social

4 Sept

Daisy approves! @ktlandon.bsky.social

Tim Fennell reposted

Ashland Poetry Press

1 Sept

@ktlandon.bsky.social 's debut collection, Abide, launches today! 2025 Richard Snyder Prize Winner, selected by @kimaddonizio.bsky.social Abide is available at @bookmobile-itasca.bsky.social , Amazon, & elsewhere now! #bookrelease #poetry #poetrycommunity #newbook #itasca #buyabook #poems

Tim Fennell reposted

Jess Smith

@nanojess.io

31 Aug

Every time I read a paper like this I just think about what a PITA it's going to be to design off-target NGS assays that are suitable for regulatory review.

Nature Biotechnology@natbiotech.nature.com

Donor-complementary prime editing enables precise kilobase and library-compatible DNA insertions - @fudanuniversity.bsky.social www.nature.com/articles/s41...

nature.comDonor-complementary prime editing enables precise kilobase and library-compatible DNA insertions - Nature BiotechnologyModular, library-compatible DNA insertions are facilitated with complementary prime editing donors.

26 Aug

dupblaster 0.3.0 is released! The new release adds: - optional tmp file compression with zstd - sequencing (optical) vs. library duplicate detection - incremental performance improvements On top of existing: - fastest and most accurate query-grouped duplicate marking - comprehensive QC stats 🧬🖥️

I think this is actually a first - I'm unaware of any streaming, query-grouped duplicate marking tool that estimates sequencing dupes and gives an adjusted library size estimate.

github.comGitHub - fulcrumgenomics/dupblaster: Blazingly fast, streaming duplicate detection for NGS dataBlazingly fast, streaming duplicate detection for NGS data - fulcrumgenomics/dupblaster

26 Aug

Found here: github.com/fulcrumgenom...

Sequencing duplicates are detected by writing a small amount per read-pair (~16 bytes) to a temp file - costs nearly no runtime. After output is closed (unblocking downstream), the temp file is read and the rate of sequencing dupes calculated. Adds maybe 2-3% to CPU used during the active phase.

Tim Fennell reposted

github.comRelease v0.7.0 · fulcrumgenomics/fgumiFor those running the fgumi command line tools v0.7.0 makes sort faster, hardens CODEC consensus, and brings dedup metrics to Picard/dupblaster parity. Sort is up to 28% faster — and 2–3× faster th...

25 Aug

fgumi v0.7.0 is released: github.com/fulcrumgenom... 1. sort is 28% faster; 2-3x faster than samtools 2. improved CODEC consensus calling 3. dedup now outputs metrics closer to picard MarkDuplicates and dupblaster 4. retag is a new tool that can copy/move/delete SAM tags

Tim Fennell reposted

Fulcrum Genomics

@fulcrumgenomics.com

24 Aug

A good case for ensuring scientific software is safe. @science-goblin.bsky.social shares what the pixy project reinforced about building code scientists can trust, maintain, and keep extending 👇

Erin McAuley@science-goblin.bsky.social

Some of the best scientific software is safe: predictable outputs, clear failures, useful tests, readable code. Working on the latest pixy update reinforced why that matters when working on scientific software. I wrote about what we learned: blog.fulcrumgenomics.com/p/how-to-wri...

blog.fulcrumgenomics.comHow to write safe software for scienceBy Erin McAuley

24 Aug

Did whoever coined "dovetailed" as the term for an NGS read-pair where the 3' ends extend past their mate's 5'-ends have *any* knowledge of woodworking? In a field of terrible names, this one wins for me because it invokes the exact opposite the originators' intent/usage.

blog.fulcrumgenomics.comA CRISPR off-target search is only as good as the sequences it searchesRebuilding DivRef so CRISPR off-target searches can account for human variation

5 Aug

Awesome forensics work by @ameynert.bsky.social to figure out all the issues and build a more robust pipeline and more complete and accurate DivRef!

Alison Meynert@ameynert.bsky.social

DivRef is a resource for including common human variants and haplotypes in CRISPR off-target searches. I rebuilt the generation workflow to make its inputs, assumptions and population choices easier to inspect and change. blog.fulcrumgenomics.com/p/a-crispr-o...

github.comGitHub - tfenne/rawb-io: Read-ahead / write-behind byte IO: threaded Reader/Writer that decouple a pipeline stage from the kernel pipe via a background thread and a byte ring bufferRead-ahead / write-behind byte IO: threaded Reader/Writer that decouple a pipeline stage from the kernel pipe via a background thread and a byte ring buffer - tfenne/rawb-io

1 Aug

Maybe three weeks ago, I* refactored some code out of dupblaster and methylsieve for using dedicated threads with large buffers for read-ahead and write-behind. Why? Because it turns out, even in Rust, it's still hard to write threading code that "just works". github.com/tfenne/rawb-io

1 Aug

Along the way I* learned about miri (github.com/rust-lang/mi...), and loom (github.com/tokio-rs/loom), both super-useful tools for hardening a library like this. rawb-io now uses both in CI, has far better testing, and provably no possible deadlocks or data races!

1 Aug

So if you're writing rust and want to move I/O off the main thread, check it out!

Tim Fennell reposted

github.comRelease v0.7.0 · fg-labs/bwa-mem30.7.0 — methylation accuracy, a sharper --fast, and broad speedups This is primarily a methylation release. The bisulfite path was reworked to a chemistry-aware contract — TAPS support, a NEUTRAL -...

23 July

bwa-mem3 v0.7.0 is out. 5–24% faster than v0.6.0, output byte-identical; upgrade and it's free. If you do methylation: reworked bisulfite path with TAPS support too. github.com/fg-labs/bwa-mem3/releases/tag/v0.7.0

Tim Fennell reposted

github.comGitHub - fg-labs/unum: Fulcrum-owned Rust HLA/KIR genotyper (strangler port of T1K)Fulcrum-owned Rust HLA/KIR genotyper (strangler port of T1K) - fg-labs/unum

14 July

unum: a pure-Rust HLA/KIR genotyper It's a port of github.com/mourisl/T1K, offering significant speedups, ergonomics, and opinionated improvements. I am looking for folks who want to give it a try and give constructive feedback. github.com/fg-labs/unum

Tim Fennell reposted

yaoi gagarin

@mel.bzky.team

11 July

well okay so the english won against the norwegians but in only a few days theyll have to face the french. anyway thats quite enough about September 25th 1066, lets look at some football news

Tim Fennell reposted

Andrew Whitwham

@whitwham.bsky.social

htslib.orgSamtoolsSamtools

Release 1.24 of HTSlib, SAMtools, and BCFtools is now available from GitHub. See htslib.org/download/ for links to tarballs and release notes. 🧪🧬🖥️

Tim Fennell reposted

github.comRelease v0.7.0 · fulcrumgenomics/ferro-hgvsAdded (reference) validate manifest schema/version at load, fail loud on an incompatible reference (#1003) (mosaic) parse predicted-wrapper and whole-entity-LHS =/ forms (#992) (protein) parse ins...

🚀 ferro-hgvs 0.7.0 is out: our biggest release yet. Major upgrades to HGVS normalization, parsing & projection: spec-compliant 3′ shifting, mosaic/compound alleles, multi-axis projection (g/c/n/p/r), Ensembl support, plus ~1.7× faster parsing. github.com/fulcrumgenom...

More fun with fable yesterday. A coworker thought they'd cracked the code by asking opus to pose questions to a fable sub-agent in Claude Code. Dear reader, they had not.

Opus found our questions about aligners and "teach me basic infosec" *so* benign it concluded the only reasonable answer was that the sub-agent system did not support fable at all. We then asked some truly benign questions, and Opus was shocked:

So TL;DR is fable for sub-agents is even worse - silently falls back to Opus with nearly no trace. CC @nilshomer.com and @robp.bsky.social.

More fun with fable yesterday. A coworker thought they'd cracked the code by asking opus to pose questions to a fable sub-agent in Claude Code. Dear reader, they had not.

Opus and I did a little experimenting and some forensics, and determined we could figure out what model a sub-agent used to render a response: