Nils Homer

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.

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

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

Want to see a mistake I made?

2.3 billion read pairs of 10x Flex v2 (281 GB of gzipped FASTQ) mapped in under 2 minutes on one machine (-t 64) with piscem-rs. That's ~20M read pairs/sec at ~87% mapped. One interesting part is the mapper, but what I want to talk about here is who gets the threads. 1/8

> then around 850-950 ad, their ceremonial centers were suddenly abandoned, and researchers still have no idea why

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...

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...

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

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...

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...

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...

🚀 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...

Save the compute, save the world!

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

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

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"

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

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`)!

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

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...

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.