Damiano Sgarbossa
@damianosg.bsky.social
740 followers 220 following 19 posts
PhD in Computational Biology & ML for Proteins @EPFL https://sites.google.com/view/damiano-sgarbossa
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damianosg.bsky.social
🎉 Excited to share that the last paper of my PhD is now published in PRX Life!

We introduce RAG-ESM, a retrieval-augmented framework that makes pretrained protein language models (like ESM2) homology-aware with minimal training cost.

📄 Paper: journals.aps.org/prxlife/abst...
damianosg.bsky.social
📢 Our new preprint is out on bioRxiv! We introduce RAG-ESM, a retrieval-augmented framework that improves pretrained protein language models like ESM2 by making them homology-aware with minimal additional training costs.
🔗 doi.org/10.1101/2025...
💻 github.com/Bitbol-Lab/r...

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RAG-ESM logo
Reposted by Damiano Sgarbossa
mjendrusch.bsky.social
With this, the last bit of my PhD at @embl.org is finally out!
We developed salad (sparse all-atom denoising), a family of blazing fast protein structure diffusion models.
Paper: nature.com/articles/s42256-…
Code: github.com/mjendrusch/salad
Data: zenodo.org/records/14711580
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embl.org
EMBL @embl.org · 16d
‘Salad’ – a new AI model from EMBL scientists – offers major improvements in synthetic protein design.

Salad is significantly faster than comparable methods, and designing proteins that don't exist in nature can have applications in many scientific fields.

www.nature.com/articles/s42...
Reposted by Damiano Sgarbossa
umbislupo.bsky.social
Two exciting openings with us! 🤖🧬🆎🧫💉
- AI Scientist 👉 lnkd.in/eDXHH4E8
- AI Scientist, Drug Creation 👉 lnkd.in/eEvGyaTR

You'll work on antibody sequence/structure design, antibody-antigen co-folding, antibody-antigen binding prediction, physics-based methodologies, and more!

DMs welcome!
damianosg.bsky.social
🎉 Excited to share that the last paper of my PhD is now published in PRX Life!

We introduce RAG-ESM, a retrieval-augmented framework that makes pretrained protein language models (like ESM2) homology-aware with minimal training cost.

📄 Paper: journals.aps.org/prxlife/abst...
damianosg.bsky.social
📢 Our new preprint is out on bioRxiv! We introduce RAG-ESM, a retrieval-augmented framework that improves pretrained protein language models like ESM2 by making them homology-aware with minimal additional training costs.
🔗 doi.org/10.1101/2025...
💻 github.com/Bitbol-Lab/r...

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RAG-ESM logo
Reposted by Damiano Sgarbossa
cyrilmalbranke.bsky.social
[1/8] 📄 New preprint! With Gionata Paolo Zalaffi & Anne-Florence Bitbol, we introduce ProteomeLM, a transformer that processes entire proteomes (prokaryotes and eukaryotes), enabling ultra-fast protein–protein interaction (PPI) prediction across the tree of life.
🔗 www.biorxiv.org/content/10.1...
ProteomeLM: A proteome-scale language model allowing fast prediction of protein-protein interactions and gene essentiality across taxa
Language models starting from biological sequence data are advancing many inference problems, both at the scale of single proteins, and at the scale of genomic neighborhoods. In this paper, we introduce ProteomeLM, a transformer-based language model that reasons on entire proteomes from species spanning the tree of life. Leveraging protein language model embeddings, ProteomeLM is trained to reconstruct masked protein embeddings using the whole proteomic context. It thus learns contextualized protein representations reflecting proteome-scale functional constraints. We show that ProteomeLM spontaneously captures protein-protein interactions (PPI) in its attention coefficients. We demonstrate that it screens whole interactomes orders of magnitude faster than amino-acid coevolution-based methods, and substantially outperforms them. We further develop ProteomeLM-PPI, a supervised PPI prediction network that combines ProteomeLM embeddings and attention coefficients, and achieves state-of-the-art performance across species and benchmarks. Finally, we introduce ProteomeLM-Ess, a supervised predictor of gene essentiality that generalizes across diverse taxa. Our results highlight the power of proteome-scale language models for addressing function and interactions at the organism level. ### Competing Interest Statement The authors have declared no competing interest. European Research Council, https://ror.org/0472cxd90, 851173
www.biorxiv.org
damianosg.bsky.social
📈 Despite its smaller size, ProtMamba is better than SOTA on conditional sequence generation and competitive with other protein language models on fitness prediction, showing the importance of long-context conditioning.

Read it here: doi.org/10.1093/bioi...
Github repo: github.com/Bitbol-Lab/P...
damianosg.bsky.social
🧬 ProtMamba applications include:
- Generating novel protein sequences conditioned on a given set of homologs,
- Inpainting specific regions within sequences,
- Modeling disordered regions of different protein sequences,
- Predicting the fitness of protein variants.
damianosg.bsky.social
⚙️ ProtMamba is based on Mamba, a state space model that efficiently handles very long sequences. The model uses a fill-in-the-middle training objective, combining autoregressive modeling and masked language modeling to predict amino acids conditioned on the given homologs.
damianosg.bsky.social
🔍 ProtMamba is homology-aware yet alignment-free, meaning it captures evolutionary information without relying on multiple sequence alignments. This allows it to avoid the imperfections of MSAs but still use the information of other homologs to condition the generation!
damianosg.bsky.social
Happy to announce that our paper, "ProtMamba: a homology-aware but alignment-free protein state space model", has been published in Bioinformatics! 🎉

doi.org/10.1093/bioi...
damianosg.bsky.social
Also, a huge thanks to my supervisor Anne-Florence and my defense committee: Bruno Correia @pschwllr.bsky.social @sokrypton.org and Thomas Lemmin
damianosg.bsky.social
I'm really happy to share with you that after 4 years at EPFL I'm finally a PhD! 🎉🎓

Last Friday I defended my thesis titled: "Revealing and Exploiting Coevolution through Protein Language Models".

It was an amazing journey where I met some incredible people. Thank you all ❤️
Reposted by Damiano Sgarbossa
1995dana.bsky.social
New preprint of @trono-lab.bsky.social and my PhD work!
By modulating SWI/SNF remodeling at ancient transposable elements - LINE/L2s and SINE/MIRs, a "noncanonical" KZFP called ZNF436 protects cardiomyocytes from losing their identity.
🫀heartbeat on 🔁 repeat
www.biorxiv.org/content/10.1... #TEsky
Reposted by Damiano Sgarbossa
bioinfo.se
In this evaluation of AlphaFold3 (and other methods), we show that (i) accurate predictions are limited to RNA structures/complexes with structural similarity to PDB and (ii) that current methods are bad at estimating the accuracy of the predictions. www.biorxiv.org/content/10.1...
Limits of deep-learning-based RNA prediction methods
Motivation: In recent years, tremendous advances have been made in predicting protein structures and protein-protein interactions. However, progress in predicting the structure of RNA, either alone or...
www.biorxiv.org
damianosg.bsky.social
This is a work that I did in collaboration with Anne-Florence Bitbol @epfl-ai-center.bsky.social. #CompBio #DeepLearning #ProteinEngineering #AI #MachineLearning #ICLR2025
damianosg.bsky.social
RAG-ESM is simple to implement, compatible with pretrained ESM2 checkpoints, and efficient to train (~50–120 GPU hours).

Come check my poster (spotlight) at the MLGenX workshop at ICLR in Singapore!

Code (still WIP): github.com/Bitbol-Lab/r...
Preprint: doi.org/10.1101/2025...

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GitHub - Bitbol-Lab/rag-esm
Contribute to Bitbol-Lab/rag-esm development by creating an account on GitHub.
github.com
damianosg.bsky.social
RAG-ESM is trained with a discrete diffusion objective, giving it generative capabilities. RAG-ESM achieves SOTA among sequence-based models for conditional generation and motif scaffolding. It outperforms DPLM (650M), EvoDiff-MSA, and ProtMamba on key benchmarks.

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damianosg.bsky.social
An unexpected result: Several cross-attention heads naturally learn to align the input and context sequences, even though the model is trained on unaligned data. This alignment capability emerges purely from the training objective (no explicit alignment supervision).

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damianosg.bsky.social
Using just one homolog as context, RAG-ESM models (12M and 165M params) outperform ESM2 (650M) on masked token prediction. We obtain a 40–50% reduction in perplexity despite using much fewer parameters.

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damianosg.bsky.social
Conditioning on homologs reduces the effective dimensionality of the search space during inference. Instead of encoding information of entire protein families internally, the model can focus its weights on more nuanced biological features.

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damianosg.bsky.social
What does RAG-ESM do?
It augments ESM2 with a few lightweight cross-attention layers that let us condition the model on retrieved homologous sequences. This allows the model to leverage evolutionary information during inference without retraining.

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damianosg.bsky.social
📢 Our new preprint is out on bioRxiv! We introduce RAG-ESM, a retrieval-augmented framework that improves pretrained protein language models like ESM2 by making them homology-aware with minimal additional training costs.
🔗 doi.org/10.1101/2025...
💻 github.com/Bitbol-Lab/r...

1/7
RAG-ESM logo
Reposted by Damiano Sgarbossa
karstenkreis.bsky.social
📢📢 "Proteina: Scaling Flow-based Protein Structure Generative Models"

#ICLR2025 (Oral Presentation)

🔥 Project page: research.nvidia.com/labs/genair/...
📜 Paper: arxiv.org/abs/2503.00710
🛠️ Code and weights: github.com/NVIDIA-Digit...

🧵Details in thread...

(1/n)
Reposted by Damiano Sgarbossa
tbepler.bsky.social
Excited to share PoET-2, our next breakthrough in protein language modeling. It represents a fundamental shift in how AI learns from evolutionary sequences. 🧵 1/13
Reposted by Damiano Sgarbossa
howard.fm
I'll get straight to the point.

We trained 2 new models. Like BERT, but modern. ModernBERT.

Not some hypey GenAI thing, but a proper workhorse model, for retrieval, classification, etc. Real practical stuff.

It's much faster, more accurate, longer context, and more useful. 🧵
Reposted by Damiano Sgarbossa
harrisbio.bsky.social
Extremely pleased to announce that after *checks notes* 2 years, our paper on Structure-based Drug Design with diffusion models has been published in Nature Computational Science (@natcomputsci.bsky.social)!!

Thanks a lot to the great co-authors! Esp
@rne.bsky.social & Yuanqi Du.
Structure-based drug design with equivariant diffusion models - Nature Computational Science
This work applies diffusion models to conditional molecule generation and shows how they can be used to tackle various structure-based drug design problems
www.nature.com