Thank you Giulio! You built something truly special when you burst onto the bioinformatics scene with SSHash. It's an amazing data structure, but even better, it led to our ongoing collaboration which has been, for me, the epitome of what is great and fun in science!
I've been wanting to do a big refactor and build system update for salmon for a looong time. I finally got around to it, and updated the backend index to use the newest SSHash while I was at it : github.com/COMBINE-lab/... (also with native ARM support & on bioconda!)
This is a false trichotomy.
Sad news, but what a long and incredible life!
I was very impressed by what it could do with the ability to introspect, benchmark, look at assembly, etc. Below is the latest state (across both AVX2 and Neon). One idea it suggested that was quite nice & clever was cache coloring to reduce L1 pressure / interference :).
Ohh, that's the cool part. Writing straight up neon and avx. Also, making good suggestions like cache coloring, which helped a lot!
Ok guys; it turns out that Claude is kind of a gangsta at optimization. Some further gains when also benchmarking & optimizing on AVX2. Now, all modes in Rust are faster than their C alternative under Neon & most are under AVX2, some substantially so:
Since it's not on @biorxivpreprint.bsky.social, my normal crowd might not see it, but I'm very excited about this recent work that, actually, started as class project in my graduate genomics class last year: eprint.iacr.org/2026/463 . Zero knowledge proofs for genomics; with algorithms :).
Ohh, I'd love Santiago's feedback on this! I was going to wait until I added some more polish, but I think Claude found a few things that could be ported back to the C implementation as well :).
Here’s my bug report, which links the C++ MRE. Curious if others see the same thing github.com/microsoft/mi....
Here’s my bug report, which links the C++ MRE. Curious if others see the same thing github.com/microsoft/mi....
Has anyone experienced instability issues (crash during teardown) when using mimalloc on MacOS? I don't see it in Rust, but it's showing up in C++, and asan on the program is clean.
Less than 48 hours later and here is where we stand. It started as a simple experiment, but, honestly, if I were doing something in Rust now, I think I'd use this rather than any of the bindings for the C implementation ;P.
Dear @anthropic.com, my lab builds a lot of OSS for genomics (github.com/COMBINE-lab). While we lack the widespread OSS market of popular NPM packages, pieces of our software are critical in biomedical research. Please consider extending your Claude Max offer to such labs!
The (native) Rust version of wfa2-lib isn't all *safe* Rust, but damn it's fast! Currently, only the Affine2p (specifically with CIGAR) really lags behind the C impl, several others are considerably *faster*.
Claude code is so cute when it gets excited:
I covered it in my class and linked to it in my slides ;). Maybe the students are looking (it's a grad class).
It is what I imagine a programming language would look like if invented by someone who actively hates programming languages, and programmers.
Spring break in Trump's America:
CMake is, perhaps, the ugliest build system ever. Thank goodness I can have an AI agent interface directly with that nonsense rather than doing it as a person. CMake wasn't meant for human interaction anyway, so perhaps we've come full circle in it's lifecycle.
Current performance story:
Sonnet also handles these tasks well; yes. Functionally, I've not noticed too much of a difference with the latest Sonnet. This is specifically true once you get to the phase of actually implementing — Opus may still be a little bit nicer for planning, but executing the phases, they work similarly.
Score-only edit distance is now slightly (~9%) *faster* than the C version. The biggest focus now, where Rust is non-trivially slower, is in affine with CIGAR and dual-affine with CIGAR.
Yes. I started with this hand-written PROJECT.md file (github.com/COMBINE-lab/...), and then used plan mode, and a few iterations, to have Claude come up with the PLAN (github.com/COMBINE-lab/...). Has worked well so far!
Functionally complete at a 2-7% performance penalty depending on the mode. Gonna try a bit more but that last few percent may need something beyond the current frontier models. Something like a @curiouscoding.nl v1.0 model might be needed.
I may play around a bit more tonight, but this is a good checkpoint: github.com/COMBINE-lab/.... All features implemented, unit and integration tests, dedicated aarch64 & avx2 backends, a driver CLI! Still a bit slower than the C version, but we're closing the gap quick!
Just put the kids to bed .... and ... we have all features implemented and the CLI! We have a feature complete WFA2-lib in native Rust.
Now, we start what I anticipate will be the longest of the 13 phases; phase 12, performance optimization. Onward!
Post ultimate Frisbee with the kids & dinner; BiWFA is done, 2-bit nucleotide encoding & lambda-based scoring are done! Next is just the CLI driver and we are "functionally complete". The last 2 stages are performance optimization & polish (docs, API cleaning, etc.).
For all implemented tasks so far, there are both unit & integration tests, and results match the C-baseline :). 2/2
Pre-dinner update (5:16 PM).
Have implemented WFA score-only, CIGAR, end-to-end, gap-linear, gap-affine, dual-gap affine, ends-free & extension as well as important heuristics.
Currently, mostly through BiWFA. Then comes lambda/custom match, packed 2-bit DNA, a binary driver program & perf opts. 1/2
