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...

A CRISPR off-target search is only as good as the sequences it searches

Rebuilding DivRef so CRISPR off-target searches can account for human variation

blog.fulcrumgenomics.com

CRISPR off-target search can find the right locus while hiding plausible alignments within it. I wrote about how Sassy v0.2.5 uses recursive backtracking to report every reasonable alignment—more than 9× as many in under 30 seconds. blog.fulcrumgenomics.com/p/why-crispr...

Why CRISPR Off-Target Search Should Report Multiple Alignments Per Locus

How Sassy enumerates every reasonable alignment without sacrificing runtime

blog.fulcrumgenomics.com

bwa-mem3 v0.8.0 is out. New --compat=bwa-mem2: byte-identical to bwa-mem2 v2.2.1, verified across 1.57B records on 6 CPU types — including ARM. Also ~13% faster, and methylation NM/MD no longer count bisulfite conversions as mismatches. github.com/fg-labs/bwa-mem3/releases/tag/v0.8.0

Release v0.8.0 · fg-labs/bwa-mem3

0.8.0 — a verified drop-in for bwa-mem2, ~13% faster, and corrected methylation tags 1. --compat=bwa-mem2 — swap in bwa-mem3 and get the same BAM The big one. Run bwa-mem3 mem --compat=bwa-mem2 ......

github.com

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

GitHub - 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 buffer

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 buffer - tfenne/rawb-io

github.com

Bioinformatics rewrites miss the relational impact tofolks that are still actively maintaining and developing the software. I've been guilty of this myself, and I'll be sharing my story soon so others can learn from it.

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

Reporting one alignment per locus can commit a CRISPR off-target analysis to one scoring model too early. @timd.one explains how Sassy v0.2.5 enumerates every reasonable alignment while keeping runtime fast: >9× as many alignments in under 30 seconds. blog.fulcrumgenomics.com/p/why-crispr...

Why CRISPR Off-Target Search Should Report Multiple Alignments Per Locus

How Sassy enumerates every reasonable alignment without sacrificing runtime

blog.fulcrumgenomics.com

grep is a fantastic tool, but it doesn't really work on sequencing data: it breaks when the pattern is in the read name, and doesn't support paired-end FASTQs. Thanks to @nilshomer.com, we have a new interactive guide on using fqgrep to find patterns in FASTQ files: ➡️ sandbox.bio/tutorials/fq...

Interactive bioinformatics tutorials

Learn bioinformatics from your browser, no setup required. Everything runs in a sandbox, so you can experiment all you want.

sandbox.bio

Start from the patient, name the real gap, then build the analysis that closes it. @fulcrumgenomics.com VP of Translational Research Juliann Chmielecki, PhD nails it. Worth your time if you work anywhere near translational oncology. www.linkedin.com/pulse/from-e...

From equations to patients: where computational biology meets translational science

Building translational strategies marries new methodologies with an unanswered clinical question, then works with the data and analyses needed to answer it When I think about what translational scienc...

linkedin.com

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

GitHub - 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

github.com

🚀 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...

Release v0.7.0 · fulcrumgenomics/ferro-hgvs

Added (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...

github.com

Save the compute, save the world!

Tim Fennell@tfenne.bsky.social · last mo.

Our blog traffic isn't high enough to get this awesome image by our graphic designer the views it deserves:

Our new genome annotation method relies almost entirely on transcriptome and alignment evidence, and as a result outperforms pretty much all other de novo pipelines. Check out the just-published paper led by Aleksey Zimin: rdcu.be/frSOg

Efficient evidence-based genome annotation with EviAnn

Nature Methods - EviAnn surpasses existing genome annotation methods by leveraging gene expression and protein sequence homology evidence to achieve higher accuracy and efficiency.

rdcu.be

#bioinformatics re-writes are more often about doing it "right" this time, rather than faster this time. #genomics #rust #rewrites

Tim Fennell@tfenne.bsky.social · 4w ago

In other news I released a tool called methylsieve ~3 weeks ago, thinking it would just be a better "filter unconverted reads" tool that'd slot in between alignment and sorting. Then I got frustrated that most tooling does m-bias filtering wrong ... now I have a version 0.2 coming soon... 🧬 🖥️ 🧵

New riker release this morning - version 0.4.0 is out! Major updates are: - New "rna" tool that ports picard CollectRnaSeqMetrics, fgbio EstimateRnaInsertSize, and much more - New global --threads option to multithread input BAM/CRAM decoding - Big performance improvements in "wgs" and "hybcap"

🚀 bwa-mem3 v0.5.0 is out 🎉 One flag to rule them all. The new --fast preset makes whole-genome alignment ~2× faster while preserving accuracy and recall. 🧵 github.com/fg-labs/bwa-...

Release v0.5.0 · fg-labs/bwa-mem3

0.5.0 (2026-07-04) Features add opt-in --seed-order seed reordering (default off, byte-identical) (#186) (04749a1) add opt-in --smem-dedup (dedup identical SMEMs before chaining) (#187) (1384972) ...

github.com

New on the Fulcrum blog: minibwa, a faster mapper from @lh3lh3.bsky.social and our @nilshomer.com Its speed is great, yes, but more interesting is the decision to revisit BWA-MEM as infrastructure – keep what still works, change what limits performance, then test downstream impact. shorturl.at/xxqeI

Minibwa: alignment is never solved

Heng Li and Nils Homer revisit BWA-MEM with a faster mapper for short reads, accurate long reads, and bisulfite sequencing data.

blog.fulcrumgenomics.com

Hey @nilshomer.com, you'd asked about this in the past: we finally got around to implementing byte-level determinism in salmon (github.com/COMBINE-lab/...). It turned out to require a lot of thought and changes, but it turns out we can do it elegantly (with RAD files) and fast (`--deterministic`)!

Release v2.2.1 · COMBINE-lab/salmon

salmon 2.2.1 The recommended 2.2.x release: it carries the full 2.2.0 feature set plus a security fix for a lz4_flex advisory pulled in by the new RAD compression. If you are on 2.2.0, upgrade. No ...

github.com

re-writes aren't just about speed dupblaster, riker, chelae, and methylsieve: the stack is being re-written, not just faster, but with the fixes we've always wanted

Tim Fennell@tfenne.bsky.social · last mo.

Realized that I released a couple of new tools last week and didn't announce anything. The first one is *dupblaster*. Samblaster inspired streaming queryname grouped duplicate marking for NGS reads: github.com/fulcrumgenom...

Realized that I released a couple of new tools last week and didn't announce anything. The first one is *dupblaster*. Samblaster inspired streaming queryname grouped duplicate marking for NGS reads: github.com/fulcrumgenom...

GitHub - fulcrumgenomics/dupblaster: Blazingly fast, streaming duplicate detection for NGS data

Blazingly fast, streaming duplicate detection for NGS data - fulcrumgenomics/dupblaster

github.com

minibwa + ALTs: github.com/nh13/minibwa... In-mapper ALT-aware MAPQ recovery via DRAGEN-style liftover groups. No bwa-postalt.js. Matches bwa+postalt, byte-identical without a .alt file. Works how I want it to. The real test will be when others give it a try. No warranty, implied or otherwise.

ALT-aware mapping via post-extension liftover groups by nh13 · Pull Request #7 · nh13/minibwa

ALT-aware mapping via post-extension liftover groups Draft for design feedback, opened against this fork's master. It adds optional ALT-contig awareness: given a .alt file, reads whose confiden...

github.com

Tim Triche, Jr.🔰@timtriche.bsky.social · last mo.

Does bwa-mem3 deal properly with alts?

🚀 new bwa-mem3 is out. Why use it? - 🏛️keep using a bwa-mem variant (avoid revalidation/reprocessing) - 🚅 1.7x faster/20% less memory than bwa-mem2 - 🧬native methylation support (asymmetric scoring) - ✅ matches bwa-mem2 output - 👊opt-in knobs to go even 2x faster bwa-mem3.readthedocs.io/en/latest/

Rust and python bindings for minibwa are available on crates.io and pypi.org: github.com/fg-labs/mini...

GitHub - fg-labs/minibwa-bindings: Rust and Python bindings for minibwa — Heng Li's lightweight bwa

Rust and Python bindings for minibwa — Heng Li's lightweight bwa - fg-labs/minibwa-bindings

github.com

Faster samtools sort, why aren't you using it? github.com/fg-labs/mako

GitHub - fg-labs/mako: Fast SAM/BAM sorter.

Fast SAM/BAM sorter. Contribute to fg-labs/mako development by creating an account on GitHub.

github.com

Minibwa is a hybrid of bwa-mem and minimap2 and the successor of bwa-mem for short-read mapping. ~4X/2.5X as fast as bwa-mem/bwa-mem2 for WGS reads at comparable accuracy. Native support of directional bisulfite-seq. Applicable to long reads. Preprint at arxiv.org/abs/2606.15357

Over the last few weeks I've been exploring writing a new short-read adapter trimming tool after running into frustrations with existing tools. Yesterday I made it public and pushed the first release to bioconda: github.com/fulcrumgenom...

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

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

github.com

I've seen lots of AI rewrites in bioinformatics lately, and I’m concerned because LLMs can be confidently wrong. What do the best tool builders do to make sure their rewrites are correct? How can we tell if a rewrite is flawed? I interviewed 5 scientists to find out: youtu.be/0o2XnEBDxrI

I interviewed 5 bioinformatics experts about AI rewrites

YouTube video by OMGenomics

youtu.be

Sort your BAMs faster! I am looking for bug-resistant early alpha testers of mako to verify the speedup cl..ai..ms. I am seeing 1.1-1.9x speedups depending on data type and workload. github.com/fg-labs/mako

holodeck built with inspiration from dwgsim, which was built with inspiration from the original @lh3lh3.bsky.social wgsim. So many levels...

Tim Fennell@tfenne.bsky.social · 4mo ago

I was sitting in talks at AGBT Ag this week, trying to simulate reads over SNP sites to bootstrap my way into doing contamination detection in domestic cats, when I got pretty frustrated with DWGSIM by @nilshomer.com who happened to be sitting right next to me. Now I have github.com/fg-labs/holo...

Catch me if you can…

Fulcrum Genomics@fulcrumgenomics.com · 4mo ago

At #AGBTAg26, @nilshomer.com will present our work with @broadinstitute.org , @umasschan.bsky.social, and Darwin's Ark on building a comprehensive imputation reference panel for domestic cats. See the flash talk today at 4:30pm during the Plenary, or catch poster #128 during the poster sessions.