Fulcrum Genomics

We hope to see you today!

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.

Belay Diagnostics needed a pipeline they could release and audit as Summit™ moved toward clinical testing. Fulcrum helped put automated tests, version control, and separate development, staging, and production environments in place. Read the case study: resources.fulcrumgenomics.com/hubfs/Fulcru...

#ASHG26 #ASHG2026 #HumanGenetics #Genomics

Fulcrum contributes to open-source bioinformatics by building new pipelines, improving those we maintain, and contributing to external projects. From faster alignment to transparent analysis, Public Benefit guides the work: solve real constraints and leave the field better.

Aggregate QC couldn’t answer Canal Biosciences’ question. We built a cycle-resolved framework to assess early-cycle errors, strand/base context, and ssDNA vs. dsDNA performance as the library-prep protocol evolved. See the case study: resources.fulcrumgenomics.com/hubfs/Fulcru...

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 👇

Did you know most clinical genomics runs on research-grade code? That code has carried the field far, but benchmarking once isn't the same as verifying across versions, edge cases, & clinical use. @nilshomer.com on tool-level verification becoming routine: blog.fulcrumgenomics.com/p/benchmarki...

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...

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 cannot report a sequence it was never given. @ameynert.bsky.social explains how DivRef brings common human variants and haplotypes into the search space—and how her rebuild complements @timd.one work on Sassy. Read Alison’s post: blog.fulcrumgenomics.com/p/a-crispr-o...

grep is indispensable—until you need to search FASTQ files correctly. We created a hands-on guide on Sandbox.bio for searching sequencing reads and paired-end data directly in your browser 👇

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...

In Q2 Fulcrum Field Notes: @nilshomer.com on AI rewrites and minibwa, @tfenne.bsky.social on Riker for deep sequencing QC and old bioinformatics plumbing. Read the Q2 issue: resources.fulcrumgenomics.com/q2-fulcrum-f...

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

Pipeline release! nf-core/fastquorum v2.0.0 - 2.0.0! Please see the changelog: https://github.com/nf-core/fastquorum/releases/tag/2.0.0

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

Open-source bioinformatics works best when the tools are fast, inspectable, and reproducible. Our recent releases cover UMI workflows, sequencing QC, reference identification, ECS analysis, and HGVS parsing. See the one-page overview: shorturl.at/uo8iX

@nilshomer.com joined Rob Patro, @ewels.bsky.social, & others to talk AI-assisted bioinformatics rewrites on the OMGenomics show. The AI-assisted rewrite is the easy part. It is proving correctness, finding edge cases, and being around to support the tool later that’s harder. youtu.be/0o2XnEBDxrI

New release of fgbio today. Major change is to pull in HTSJDK 5 for big bumps to BAM and CRAM read/write performance, as well as full CRAM 3.1 read/write support! github.com/fulcrumgenom...

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

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...

The bioinformatics community has been waiting for a modern home for the DuplexSeq method. We supported Scantox in migrating the pipeline onto Latch, validated outputs against TwinStrand's original datasets, and rebuilt the foundation so it can keep evolving with current research. shorturl.at/VmqBT

Deep QC should run on every sequencing dataset. In a new post, Fulcrum co-founder @tfenne.bsky.social explains why he built Riker, a modern successor to Picard designed to make rich sequencing QC fast enough to run every time. Blog: shorturl.at/oUTXk Repo: github.com/fulcrumgenom...

Oncology pipelines don’t stay where they were first built. They move across teams, infra, and timelines, and can start to get brittle. So we built twistcgp with @twistbioscience.com as an nf-core-based workflow for analyzing data from the Twist Oncology DNA CGP Panel. github.com/fulcrumgenom...

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.

With CacheDNA we benchmarked ensilication for room‑temp DNA storage vs −80°C. Results: -100% concordance on clinical FFPE lung panel down to ~2% VAF -65% more artifactual C>T mutations at -80C than ensilication in WGS What this means for oncology, TMB, and global genomics: shorturl.at/ZqUck

Bioinformatics tools usually emit the final result and discard everything that led to it. That missing signal is exactly what ML models need to learn from. Fulcrum co-founder @nilshomer.com makes the case that next generation tools should be AI-ready. 🔗 blog.fulcrumgenomics.com/p/your-bioin...

Our #bioinformatics leader & VP of Ops, @moonlight.bio, will be at #PMWC26 March 4–6 in Santa Clara. PMWC continues to push the field toward turning complex biological data into real decisions. Clint will be on-site connecting with teams advancing #genomics and #PrecisionMedicine.

@tfenne.bsky.social and @nilshomer.com are on the ground at #AGBT2026 this week. Big data. Tight timelines. Real decisions. #Bioinformatics is where complexity becomes something teams can actually use. If you’re here, let’s connect.

Today is International Day of Women and Girls in Science. Grateful for the women who design studies, wrangle messy data & ask the hard questions that move research forward. Your expertise makes science stronger every day. #WomenInScience

In translational/clinical work we see bioinformatics projects fail not due to science, but because early assumptions box the data in. We plan with downstream reality in mind: biology, existing data, constraints that matter. That’s how teams move fast without rework. Let’s chat & scope your project

A new *Nature Genetics* paper co-authored by Alison Meynert maps the signalling effects of every possible CTNNB1 exon 3 missense mutation. Variants in the same hotspot can differ substantially in effect. More in our blog post ↓ blog.fulcrumgenomics.com/p/why-functi...

In this final edition of our Meet the Team series, we introduce a teammate whose perspective reflects a simple premise: molecules don’t lie. After these brief interviews we hope you feel like you know each of us a little better — or want to. Meet Jess Smith: blog.fulcrumgenomics.com/p/meet-jess-...

Most teams don’t struggle with ideas, just the momentum to get there quickly. We can help. “Start with a concept, describe the desired outcome and they can build the tools to make you successful.” — Keith Brown, Founder, Jumpcode Genomics

UMI consensus isn’t hard. Making it reproducible is. Our answer to reproducibility is fastquorum, an nf-core pipeline that turns fragile, one-off UMI workflows into something boring and reliable. No hype. Just infrastructure that works. 👉 www.linkedin.com/pulse/fastqu...