Biologist and programmer @chapmanb.bsky.social @chapmanb@spore.social

Boston, MA
Joined December 2008
Brad Chapman retweeted
The main preprint from my postdoc is live! biorxiv.org/content/10.64898… The core idea is to try to make synthetic biology much more systematic and precise, akin to more mature fields of engineering. This was an ambitious project, it started all the way back in February of 2020 and is only just now wrapping up! Thankfully there were no events in that timeframe, either around the world or specifically here at Harvard, that made things any more difficult than they needed to be. The fundamental dilemma is that we are often forced to do one of two things when designing a synthetic circuits: either we can navigate a laborious design-build-test cycle where we iteratively optimize a circuit's performance tuning one parameter at a time, or we can screen a huge array of variants using techniques like directed evolution and pick the winners and have little insight into the molecular details of why one design worked better than the others. Our idea was to try to get the best of both worlds, to combine precise mechanistic insights with extremely high throughput in such a way that we could systematically study the whole design space of a given circuit architecture.
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Excited to share ReRoute, our new framework for scientific counterfactual prediction: informed by partial physics knowledge for much better generalization. 🌍 AI models can be remarkably accurate on familiar data, yet struggle with scientific ‘what-if’ questions The key idea: Combine observational data with partial physical knowledge to predict unseen interventions—without requiring new controlled experiments. Instead of retraining models on expensive new simulations, ReRoute uses known partial physical mechanisms to guide pretrained models through lightweight fine-tuning on existing data. The results: 🌍 Up to 31.8% lower prediction error under severe CO₂ distribution shifts in climate emulators. 🔬 Up to 89.6% lower counterfactual error in controlled advection–diffusion experiments. ⚡ No new intervention data. No retraining from scratch. Just lightweight fine-tuning. We also establish a causal identification result under explicit structural assumptions, with a machine-checked proof in Lean. The bigger picture: Scientific AI doesn't always need more data or bigger models to generalize beyond what it has seen. Sometimes, knowing just a little about how the world works can make a big difference. @Dingling_Yao @kahaan_gandhi @FrancescoLocat8 @Caltech 📄 Paper: arxiv.org/abs/2610.02252 #AIforScience #ScientificML #ClimateAI #CausalInference #PhysicsAI
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Brad Chapman retweeted
Lift-off! Aligning 30x HiFi HG002 in less than 60 seconds on 64 cores. - 128c: 33s/59s un/sorted CRAM - CRAM output reduces output size by 2.5x - Better SNP, INDEL, SV F1s - Lower peak memory It's a PoC for now! @lh3lh3 I'll start porting some of it to mm2 soon.
How much faster can we map and align accurate long reads? I benchmarked pbmm2 on 30× HiFi HG002 against GRCh38 using 64 CPU cores: ~17 minutes. Can we get below 2 minutes while maintaining SNV, INDEL, and SV calling metrics? mm2 was a jump. Is it time to leap?
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Brad Chapman retweeted
A fantastic metabolic engineering paper that: creates & regenerates a ~new cofactor (NUDH) engineers several enzymes in a ~new CO2 fixation pathway to utilize NUDH achieves impressive growth rates using a CO2/methanol feedstock & produces several products! nature.com/articles/s41467-0…
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Brad Chapman retweeted
FYI I wrapped a lot of immuno-informatics predictors so you don't have to: openvax.github.io/mhctools/ (eg NetMHCpan, MHCflurry, Pepsickle, DeepTAP, ERAMER, BigMHC, PRIME, &c)
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I made SpliceCraft a Claude Skill! Waiting on the manual review but should be live real soon. For anyone not using Claude, I made agent side-doors that give agents full access to all the functions of SpliceCraft directly. Powerful cloning tool, deeply vetted, and made with love💚
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Brad Chapman retweeted
Camilo's PLR visualizer is a beast, this is without a doubt the most powerful digital twin application in lab automation that I know of
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Brad Chapman retweeted
Today, along with @Apheris_AI, we're introducing the Antibody Developability Consortium, with @AbbVie, @argenxglobal, @LundbeckUS, and @TakedaPharma as founding members. The Consortium helps pharmaceutical and biotech companies predict manufacturability and developability risks earlier by building the field’s largest standardized antibody developability dataset. Read the full press release here: hubs.la/Q04yyRk10
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Brad Chapman retweeted
Wrote a short blog about the "shape" of language models, and the tradeoffs they may present in the future. I genuinely think it's a valuable research direction to start thinking about now, especially w.r.t. harness design. alexzhang13.github.io/blog/2…
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Brad Chapman retweeted
🎓 I’m teaching CIS 6270: Discrete Generative Models at @Penn this fall! It’s a math-first course on modern generative modeling across continuous and discrete spaces, with full derivations, code, worked examples, and current research. Follow along with us this semester! 👇 cis6270.github.io/ We start this semester with core probability, ODEs/SDEs, the continuity and Fokker-Planck equations, and then derive flow matching and score matching through DDPM, DDIM, probability-flow ODEs, along with both single- and multi-objective guidance. 🌊 Then, we rebuild the story in discrete space. 🎲 That means CTMCs and master equations, time reversal, MDLM, D3PM, block diffusion, discrete scores and guidance, followed by discrete flow matching with jump processes and simplex-based flows. 🦘 We also go well beyond the standard material: multi-objective guidance, rectified flows, and a full lecture on modern flow maps, including consistency + shortcut models, categorical/discrete flow maps, Meta Flow Maps, expanding state spaces, and strong stochastic flow maps. 🗺️ We finish by connecting generation to optimal transport, stochastic optimal control, and path-space methods, working from Wasserstein geometry and Sinkhorn through Girsanov, Doob transforms, Schrödinger bridges, and modern continuous and discrete bridge-matching methods. 🌉 Throughout the semester, on the website, we’ll be releasing the lecture slides (you can see how deliberate they are!), project descriptions, exams + full solutions, and accompanying code on HuggingFace! 🤗 Our goal is that someone can start from the foundations and follow the math all the way to the newest papers. 📚 By the end, you should have the tools to turn your own research ideas into papers for the main conferences. Just promise me we won’t be the reason ICLR goes from 60k submissions to 70k! 😅 I’m incredibly grateful to my TAs (also my PhD students), for helping me build and teach all of this: @SophieVincoff @TongChen321 @RosieZ0512! 🥰 We hope you enjoy the material! 🥳
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Brad Chapman retweeted
ʙɪɴᴅᴄʀᴀꜰᴛ2 is out, and we're not waiting for the paper. The full code drops today, free for academic and industry use. We're releasing it early so you can start designing right now, and bring its full power to the current Adaptyv competition. github.com/PacesaLab/BindCra…
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Brad Chapman retweeted
Cell–cell interactions are key to all biological processes, but there hasn't been a good way to perform inter-cellular screens for genetic regulators of these interactions in vivo. We developed match-seq (multiplexed associative tagging of cell interaction histories) - using engineered virus-like particles to transfer barcoded mRNAs from 'sender' to neighboring 'receiver' cells, so you can reconstruct cellular interactions with sequencing alone, no imaging required. We coupled match-seq with CRISPR + scRNA-seq in cancer, revealing cancer-immune interaction neighborhoods at scale, and new cancer genes that can be targeted for tumor rejection via immune cell interactions. Led by the brilliant @peterdu_ with Bassik lab! biorxiv.org/content/10.64898…
CRISPR screens are great at telling you what a gene is doing inside your cells. But what if you're interested in what's happening to its neighbors? Today, I'm excited to share match-seq, a new method that deciphers cell-cell interactions using barcoded RNA transfer. 1/9
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Brad Chapman retweeted
As better models rapidly eat the stack, what system research problems will remain to enable the next frontier of data agents? We studied the evolution of data agent capabilities the past 2 years, finding general coding agents beat hand-designed data agents by up to 37 points, with 4× fewer turns. So what's actually left for system researchers to solve? More than you might think... 📚 Paper: arxiv.org/abs/2609.03141 🧵👇
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Brad Chapman retweeted
Don’t optimize the proxy. Optimize your whole scientific system. Here, making the enzyme faster does not necessarily make the cell produce more. The terminal enzyme NeuB consumes phosphoenolpyruvate, a metabolite the cell also needs for growth and central metabolism. Pushing that reaction too hard can therefore hurt the pathway as a whole. Wang and coauthors use DLCatalysis to rank 6,612 NeuB variants. The model combines ProtT5 protein-sequence embeddings with molecular fingerprints and graph-based substrate representations, then uses bidirectional cross-attention to learn how the enzyme and substrate interact. Crucially, they do not test only the highest-ranked mutants. They deliberately sample across the predicted activity range. That reveals the important result: a less active NeuB variant raises NeuAc production from 8.54 to 9.27 g L⁻¹, because it better balances product formation with the cell’s competing metabolic needs. Use ML to explore the trade-offs of the whole system, not just to maximize a local score. Wang et al., Nature Communications (2026), CC BY-NC-ND 4.0. doi.org/10.1038/s41467-026-7…
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Brad Chapman retweeted
AI agents can run bioinformatics analyses. But can they tell when an analysis should never have been run? AI agents are getting better at running bioinformatics workflows. But who checks whether the analysis should have been run in the first place? I’m building BioNexus — an open-source Scientific Reliability Layer for Agentic Biology. It is not another AI scientist, bioinformatics platform, or workflow orchestrator. BioNexus sits between an agent and biological computation: Intent → Preflight → Existing tools → Audit → Evidence → Verify Example: “Run differential expression between these two cell clusters.” A coding agent may happily return hundreds of significant genes. BioNexus can instead detect pseudoreplication, refuse the invalid analysis, explain why, and recommend pseudobulk analysis using biological replicates. Core ideas: • deterministic scientific invariants • fail-closed execution • explicit evidence ceilings • no silent backend substitution • Claim–Evidence Ledger • BioFailureBench for biological failure modes • stable vs experimental capability separation The goal is not to make AI do more biology. The goal is to make AI know when not to compute, when not to trust a result, and when not to make a claim. BioNexus v0.10.0 is now entering a reliability/stabilization phase, with current flagship work focused on: 🧬 pseudobulk DE validity 🔬 cell annotation evidence 🗺️ spatial inference validity I’m especially interested in feedback from computational biologists working with single-cell and spatial transcriptomics. GitHub: github.com/HERRY423/BioNexus PRs, failure cases, adversarial examples, and real-world analysis scenarios are very welcome. Maybe the next bottleneck for scientific agents is not capability — but scientific restraint.
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Brad Chapman retweeted
Learning resources play a key role in shaping where talent goes. Today I’m launching my side project, BioTorch, in public beta to give researchers a clearer path into biological AI. LLMs have a wealth of great tutorials, courses, and minimal implementations from great teachers. They make the path from curiosity to contribution easy to see and offer researchers from fields like math or physics a legible roadmap to transition into AI research. In bio AI, that path is much harder to piece together. That friction can mean fewer researchers entering the field, fewer startups getting built, and less investment allocated to promising ideas. This ultimately leads to fewer life-saving cures being discovered than would otherwise be possible. BioTorch is my attempt to help change that. It starts with 116 PyTorch exercises and 17 model guides. You implement the building blocks, test your code, and see how the pieces fit into seminal models like AlphaFold2, ESM2, and RFdiffusion. The goal is to make influential papers in bio AI something you can understand and build on, bringing researchers up to the frontier as rapidly as possible. I want more people working on biology’s hardest problems. My mission is to help researchers find their way into the field, and BioTorch is the result of that ambition. BioTorch is completely free while in beta. Try your first problem now! biotorch.chrishayduk.com
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Brad Chapman retweeted
Very excited to announce the PyLabRobot Cookbook from the Chory Lab! This cookbook showcases many usage examples and design patterns that should help you get started writing PyLabRobot code quickly. I strongly recommend this cookbook to anyone interested in lab automation!
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Brad Chapman retweeted
Introducing the Tamarind Model Router. You want to know which molecular AI model will work best for this specific input, not which model wins on average. Tamarind runs hundreds of scientific AI models, and picks the best tool for the job. buff.ly/lzL1wNY
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Brad Chapman retweeted
The art of assay design is vastly underappreciated & a huge source of alpha in biotech. Lauren, Scott & Hugo give a behind-the-scenes look at @OctantBio's work in generating the CYP assays and data for the latest OpenADMET blind challenge. openadmet.github.io/octant-c…
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Brad Chapman retweeted
1/ Let’s face it: we synthetic biologists are control freaks. We want every component to do exactly what we intend and nothing else. Our new paper asks what happens if we stop fighting biological “messiness”. @DukeBiodesign @DukeUBME nature.com/articles/s41467-0…
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