PhD student at MIT Micro. Genomic language models, Metagenomics, phage enthusiast, Dead Head.

Cambridge, MA
Joined January 2022
Excited to share our preprint! A new logic for bacterial immune signaling: second messengers released from tRNAs rather than built from free nucleotide precursors. biorxiv.org/content/10.64898…
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Jordan Hoff retweeted
Introducing Microbiome Repo, a catalog of every public human gut metagenome (>500k samples) with metadata pulled straight from sequence archives, papers, and supplements olmlab.github.io/microbiome_… Published gut metagenomes? Search your name and see if it got your study!
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Jordan Hoff retweeted
Bioinformaticians have been writing the same abstract for decades - luispedro.substack.com/p/bio…
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Genomes are full of dark matter of unknown functions. We present Minerva, a new method for discovery guided by genome language models. Minerva reveals the interactions hidden in non-coding DNA, pointing to hundreds of new putative RNAs and repetitive elements per bacterial genome. Minerva allows us to find and study elements invisible to traditional methods at orders of magnitude greater scale than before.
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Jordan Hoff retweeted
Can genomic language models design biological systems to access new regions of chemical space? Some of the most complex molecules in nature are made by biosynthetic gene clusters: massive enzymes that carry out complex chemistry. But engineering these systems is challenging due to complex cross-domain interactions. To solve this, we applied gLM2 to controllably generate new domain architectures by learning from vast evolutionary data.
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Microbial intergenic regions encode much of the regulatory and functional logic of the genome, but they remain among the hardest sequences to systematically discover and annotate. We trained a sparse autoencoder on gLM2 to identify recurring patterns across hundreds of millions of microbial intergenic regions, without requiring a predefined motif, RNA family, or annotation. Those features are now integrated into SeqHub multimodal search, where they can be searched together with proteins, Pfam domains, Rfam families, taxonomy, and genomic context. Using this framework, we identified divergent members of known RNA families, and found previously uncharacterized structured RNAs and candidate regulatory elements beyond existing annotation models. The goal is to make microbial noncoding sequence space systematically searchable: discover an intergenic pattern, trace where it occurs across evolution, and use its conserved genomic context to generate hypotheses about function. Explore: seqhub.org Paper: tatta.bio/intergenic-sae Co-Authors: Nicolo Zulaybar, Matt Tranzillo, Rachel Silverstein, @Micro_Yunha, @ancornman1 This work is supported by @MooreFound and @SchmidtFutures
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Jordan Hoff retweeted
My lab and @GeneWeiLiLab at @MITBiology are recruiting a joint postdoctoral fellow to develop foundational datasets for modeling bacterial phenotypes from genotype. We are seeking candidates with experience in technology development, high-throughput library generation, and metabolomics. Job posting: careers.peopleclick.com/care…
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Extremely useful paper diagnosing why SAEs on certain models are swamped with dead neurons with prescriptions on how to fix them
A sparse autoencoder aims to learn a dictionary of interpretable features from a model's activations — but a lot can come out "dead," never firing once. On some models this is rare; on others, >70% die even with fixes like AuxK. We went down a rabbit hole to understand why...
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Jordan Hoff retweeted
Max-pooling sparse features > mean-pooling dense features Pooling nerds will enjoy this part of the ESMC interpretability work. Protein language models have to capture *everything* about a sequence, including the organism that the sequence came from, its structural fold, etc in order to be able predict amino acids. If a functional signal (e.g. active site, allostery) is local in sequence space, it may be drowned out by mean-pooling. Max-pooling across sparse features preserves this signal, and we show that it improves functional homolog recovery in the presence of decoys.
Replying to @ebetica
Furthermore, if we maxpool the features across the sequence dimension, we reduce the effect from low frequency averaging of dense embeddings, and get a vocabulary of strongly activated functional features for each protein. In fact, now we can use some of the common techniques found in information retrieval, such as TF-IDF and BM25 [our Jaccard similarity is close to this] for protein search.
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🚀 Excited to share our new work: Absolute Stability Predictor! 📊: forms.gle/4ZnXZSnTBvaykkAi9 Built the MGnify Stability Dataset (1.8M+ measurements) and developed stability prediction models, together with @grocklin, @KotaroTsuboyama, @sokrypton, and teams.
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Excited to share our discovery of a new programmable RNA-guided DNA-targeting system hiding inside bacteriophages that predates CRISPR. We call it VIPR (Viral Interference Programmable Repeat), and it uses an entirely new logic to find its targets. Thread + link below.
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🥳 Huge preprint 🔔 Today we share something our group has been working toward for a long time, led by @LucasMoriniere We asked can we predict which receptor a phage targets from its genome sequence alone? For most phages, we couldn’t. So Lucas set out to do something crazy!
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Big news! Starting my lab as Ramón y Cajal PI at @IBVF_Sevilla in Seville 🌞, Spain, bridging microbial ecology, photosynthesis & plant biotech: from metagenomic and AI analyses 💻 to experiments in microbes & plants 🌊🧬🌱 Looking for PhD students & postdocs. DM or share!
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Happy to see this project that started during my PhD come to completion! Beautiful work by @AlexanderRotsch and team solving the structure of the influenza polymerase/elongating RNA polymerase II complex. Congrats to everyone for the amazing story! nature.com/articles/s41586-0…
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Predicting protein-protein interactions (PPIs) at proteome scale can take months with co-folding models due to massive all-vs-all comparisons required. We are excited to announce FlashPPI, a contrastive model that predicts proteome wide physical interfaces in minutes. 1/🧵
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We identify conjugative megaplasmids in the human gut that embed intact temperate prophage genomes and may enable cross-lineage viral dissemination.   We propose a plasmid-mediated route for temperate phage spread. biorxiv.org/cgi/content/shor…
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Introducing DroPE: Extending the Context of Pretrained LLMs by Dropping Their Positional Embeddings pub.sakana.ai/DroPE/ We are releasing a new method called DroPE to extend the context length of pretrained LLMs without the massive compute costs usually associated with long-context fine-tuning. The core insight of this work challenges a fundamental assumption in Transformer architecture. We discovered that explicit positional embeddings like RoPE are critical for training convergence but eventually become the primary bottleneck preventing models from generalizing to longer sequences. Our solution is radically simple: We treat positional embeddings as a temporary training scaffold rather than a permanent architectural necessity. Real-world workflows like reviewing massive code diffs or analyzing legal contracts require context windows that break standard pretrained models. While models without positional embeddings (NoPE) generalize better to these unseen lengths, they are notoriously unstable to train from scratch. Here, we achieve the best of both worlds by using embeddings to ensure stability during pretraining and then dropping them to unlock length extrapolation during inference. Our approach unlocks seamless zero-shot context extension without any expensive long-context training. We demonstrated this on a range of off-the-shelf open-source LLMs. In our tests, recalibrating any model with DroPE requires less than 1% of the original pretraining budget, yet it significantly outperforms established methods on challenging benchmarks like LongBench and RULER. We have released the code and the full paper to encourage the community to rethink the role of positional encodings in modern LLMs. Paper: arxiv.org/abs/2512.12167 Code: github.com/SakanaAI/DroPE
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