The prediction of peptide-MHC (pMHC) recognition by αβ T-cell receptors (TCRs) remains a major biomedical challenge. Here, we develop STAPLER (Shared TCR And Peptide Language bidirectional Encoder Representations from transformers), a transformer language model that uses a joint TCRalphabeta-peptide input to allow the learning of patterns within and between TCRalphabeta and peptide sequences that encode recognition. First, we demonstrate how data leakage during negative data generation can confound performance estimates of neural network-based models in predicting TCR-pMHC specificity. We then demonstrate that, because of its pre-training and fine-tuning masked language modeling tasks, STAPLER outperforms both neural network-based and distance-based ML models in predicting the recognition of known antigens in an independent dataset, in particular for antigens for which little related data is available. Based on this ability to efficiently learn from limited labeled TCR-peptide data, STAPLER is well-suited to utilize growing TCR-pMHC datasets to achieve accurate prediction of TCR-pMHC specificity.
Primary systemic therapy (PST) is the treatment of choice in patients with locally advanced breast cancer and is nowadays also often used in patients with early-stage breast cancer. Although imaging remains pivotal to assess response to PST accurately, the use of imaging to predict response to PST has the potential to not only better prognostication but also allow the de-escalation or omission of potentially toxic treatment with undesirable adverse effects, the accelerated implementation of new targeted therapies, and the mitigation of surgical delays in selected patients. In response to the limited ability of radiologists to predict response to PST via qualitative, subjective assessments of tumors on magnetic resonance imaging (MRI), artificial intelligence–enhanced MRI with classical machine learning, and in more recent times, deep learning, have been used with promising results to predict response, both before the start of PST and in the early stages of treatment. This review provides an overview of the current applications of artificial intelligence to MRI in assessing and predicting response to PST, and discusses the challenges and limitations of their clinical implementation.
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