--- license: cc-by-nc-nd-4.0 --- # FusOn-pLM: A Fusion Oncoprotein-Specific Language Model via Focused Probabilistic Masking ![image/png](https://cdn-uploads.huggingface.co/production/uploads/64cd5b3f0494187a9e8b7c69/eR38p4VJhWJhwsqjZZdYp.png) In this work, we introduce **FusOn-pLM**, a novel pLM that fine-tunes the state-of-the-art [ESM-2-650M](https://huggingface.co/facebook/esm2_t33_650M_UR50D) protein language model (pLM) on fusion oncoprotein sequences, those that drive a large portion of pediatric cancers but are heavily disordered and undruggable. We specifically introduce a novel masked language modeling (MLM) strategy, employing a binding-site probability predictor to focus masking on key amino acid residues, thereby generating more optimal fusion oncoprotein-aware embeddings. Our model improves performance on both fusion oncoprotein-specific benchmarks and disorder prediction tasks in comparison to baseline ESM-2 representations, as well as manually-constructed biophysical embeddings, motivating downstream usage of FusOn-pLM embeddings for therapeutic design tasks targeting these fusions. Please feel free to try out our embeddings and reach out if you have any questions! **How to generate FusOn-pLM embeddings for your fusion oncoprotein:** ``` from transformers import AutoTokenizer, AutoModel import torch # Load the tokenizer and model model_name = "ChatterjeeLab/FusOn-pLM" tokenizer = AutoTokenizer.from_pretrained(model_name) model = AutoModel.from_pretrained(model_name) # Example fusion oncoprotein sequence: MLLT10:PICALM, associated with Acute Myeloid Leukemia (LAML) # Amino acids 1-80 are derived from the head gene, MLLT10 # Amino acids 81-119 are derived from the tail gene, PICALM sequence = "MVSSDRPVSLEDEVSHSMKEMIGGCCVCSDERGWAENPLVYCDGHGCSVAVHQACYGIVQVPTGPWFCRKCESQERAARVPPQMGSVPVMTQPTLIYSQPVMRPPNPFGPVSGAQIQFM" # Tokenize the input sequence inputs = tokenizer(sequence, return_tensors="pt") # Get the embeddings with torch.no_grad(): outputs = model(**inputs) # The embeddings are in the last_hidden_state tensor embeddings = outputs.last_hidden_state # Convert embeddings to numpy array (if needed) embeddings = embeddings.squeeze(0).numpy() print("Per-residue embeddings shape:", embeddings.shape) ``` ## Repository Authors [Sophia Vincoff](mailto:sophia.vincoff@duke.edu), PhD Student at Duke University
[Pranam Chatterjee](mailto:pranam.chatterjee@duke.edu), Assistant Professor at Duke University Reach out to us with any questions!