Recent advancements in computational biology have drawn compelling parallels between protein sequences and linguistic structures, highlighting the need for sophisticated tokenization methods that capture the intricate evolutionary dynamics of protein sequences. Current subword tokenization techniques, primarily developed for natural language processing, often fail to represent protein sequences' complex structural and functional properties adequately. This study introduces evoBPE, a novel tokenization approach that integrates evolutionary mutation patterns into sequence segmentation, addressing critical limitations in existing methods. By leveraging established substitution matrices, evoBPE transcends traditional frequency-based tokenization strategies. The method generates candidate token pairs through biologically informed mutations, evaluating them based on pairwise alignment scores and frequency thresholds. Extensive experiments on human protein sequences show that evoBPE performs better across multiple dimensions. Domain conservation analysis reveals that evoBPE consistently outperforms standard Byte-Pair Encoding, particularly as vocabulary size increases. Furthermore, embedding similarity analysis using ESM-2 suggests that mutation-based token replacements preserve biological sequence properties more effectively than arbitrary substitutions. The research contributes to protein sequence representation by introducing a mutation-aware tokenization method that better captures evolutionary nuances. By bridging computational linguistics and molecular biology, evoBPE opens new possibilities for machine learning applications in protein function prediction, structural modeling, and evolutionary analysis.

Motivation: An adjuvant is a chemical incorporated into vaccines that enhances their efficacy by improving the immune response. Identifying adjuvant names from cancer vaccine studies is essential for furthering research and enhancing immunotherapies. However, the manual curation from the constantly expanding biomedical literature poses significant challenges. This study explores the automated recognition of vaccine adjuvant names using Large Language Models (LLMs), specifically Generative Pretrained Transformers (GPT) and Large Language Model Meta AI (Llama). Methods: We utilized two datasets: 97 clinical trial records from AdjuvareDB and 290 abstracts annotated with the Vaccine Adjuvant Compendium (VAC). GPT-4o and Llama 3.2 were employed in zero-shot and few-shot learning paradigms with up to four examples per prompt. Prompts explicitly targeted adjuvant names, testing the impact of contextual information such as substances or interventions. Outputs underwent automated and manual validation for accuracy and consistency. Results: GPT-4o attained 100% Precision across all situations while exhibiting notable improve in Recall and F1-scores, particularly with incorporating interventions. On the VAC dataset, GPT-4o achieved a maximum F1-score of 77.32% with interventions, surpassing Llama-3.2-3B by approximately 2%. On the AdjuvareDB dataset, GPT-4o reached an F1-score of 81.67% for three-shot prompting with interventions, surpassing Llama-3.2-3 B's maximum F1-score of 65.62%. Conclusion: Our findings demonstrate that LLMs excel at identifying adjuvant names, including rare variations of naming representation. This study emphasizes the capability of LLMs to enhance cancer vaccine development by efficiently extracting insights. Future work aims to broaden the framework to encompass various biomedical literature and enhance model generalizability across various vaccines and adjuvants.

Tokenization is a crucial step in processing protein sequences for machine learning models, as proteins are complex sequences of amino acids that require meaningful segmentation to capture their functional and structural properties. However, existing subword tokenization methods, developed primarily for human language, may be inadequate for protein sequences, which have unique patterns and constraints. This study evaluates three prominent tokenization approaches, Byte-Pair Encoding (BPE), WordPiece, and SentencePiece, across varying vocabulary sizes (400-6400), analyzing their effectiveness in protein sequence representation, domain boundary preservation, and adherence to established linguistic laws. Our comprehensive analysis reveals distinct behavioral patterns among these tokenizers, with vocabulary size significantly influencing their performance. BPE demonstrates better contextual specialization and marginally better domain boundary preservation at smaller vocabularies, while SentencePiece achieves better encoding efficiency, leading to lower fertility scores. WordPiece offers a balanced compromise between these characteristics. However, all tokenizers show limitations in maintaining protein domain integrity, particularly as vocabulary size increases. Analysis of linguistic law adherence shows partial compliance with Zipf's and Brevity laws but notable deviations from Menzerath's law, suggesting that protein sequences may follow distinct organizational principles from natural languages. These findings highlight the limitations of applying traditional NLP tokenization methods to protein sequences and emphasize the need for developing specialized tokenization strategies that better account for the unique characteristics of proteins.

Detecting protein-protein interactions (PPIs) is crucial for understanding genetic mechanisms, disease pathogenesis, and drug design. However, with the fast-paced growth of biomedical literature, there is a growing need for automated and accurate extraction of PPIs to facilitate scientific knowledge discovery. Pre-trained language models, such as generative pre-trained transformers (GPT) and bidirectional encoder representations from transformers (BERT), have shown promising results in natural language processing (NLP) tasks. We evaluated the performance of PPI identification of multiple GPT and BERT models using three manually curated gold-standard corpora: Learning Language in Logic (LLL) with 164 PPIs in 77 sentences, Human Protein Reference Database with 163 PPIs in 145 sentences, and Interaction Extraction Performance Assessment with 335 PPIs in 486 sentences. BERT-based models achieved the best overall performance, with BioBERT achieving the highest recall (91.95%) and F1-score (86.84%) and PubMedBERT achieving the highest precision (85.25%). Interestingly, despite not being explicitly trained for biomedical texts, GPT-4 achieved commendable performance, comparable to the top-performing BERT models. It achieved a precision of 88.37%, a recall of 85.14%, and an F1-score of 86.49% on the LLL dataset. These results suggest that GPT models can effectively detect PPIs from text data, offering promising avenues for application in biomedical literature mining. Further research could explore how these models might be fine-tuned for even more specialized tasks within the biomedical domain.

In the realm of online privacy, privacy assistants play a pivotal role in empowering users to manage their privacy effectively. Although recent studies have shown promising progress in tackling tasks such as privacy violation detection and personalized privacy recommendations, a crucial aspect for widespread user adoption is the capability of these systems to provide explanations for their decision-making processes. This paper presents a privacy assistant for generating explanations for privacy decisions. The privacy assistant focuses on discovering latent topics, identifying explanation categories, establishing explanation schemes, and generating automated explanations. The generated explanations can be used by users to understand the recommendations of the privacy assistant. Our user study of real-world privacy dataset of images shows that users find the generated explanations useful and easy to understand. Additionally, the generated explanations can be used by privacy assistants themselves to improve their decision-making. We show how this can be realized by incorporating the generated explanations into a state-of-the-art privacy assistant.

Computational models that accurately predict the binding affinity of an input protein-chemical pair can accelerate drug discovery studies. These models are trained on available protein-chemical interaction datasets, which may contain dataset biases that may lead the model to learn dataset-specific patterns, instead of generalizable relationships. As a result, the prediction performance of models drops for previously unseen biomolecules, $\textit{i.e.}$ the prediction models cannot generalize to biomolecules outside of the dataset. The latest approaches that aim to improve model generalizability either have limited applicability or introduce the risk of degrading prediction performance. Here, we present DebiasedDTA, a novel drug-target affinity (DTA) prediction model training framework that addresses dataset biases to improve the generalizability of affinity prediction models. DebiasedDTA reweights the training samples to mitigate the effect of dataset biases and is applicable to most DTA prediction models. The results suggest that models trained in the DebiasedDTA framework can achieve improved generalizability in predicting the interactions of the previously unseen biomolecules, as well as performance improvements on those previously seen. Extensive experiments with different biomolecule representations, model architectures, and datasets demonstrate that DebiasedDTA can upgrade DTA prediction models irrespective of the biomolecule representation, model architecture, and training dataset. Last but not least, we release DebiasedDTA as an open-source python library to enable other researchers to debias their own predictors and/or develop their own debiasing methods. We believe that this python library will corroborate and foster research to develop more generalizable DTA prediction models.

An entity mention in text such as "Washington" may correspond to many different named entities such as the city "Washington D.C." or the newspaper "Washington Post." The goal of named entity disambiguation is to identify the mentioned named entity correctly among all possible candidates. If the type (e.g. location or person) of a mentioned entity can be correctly predicted from the context, it may increase the chance of selecting the right candidate by assigning low probability to the unlikely ones. This paper proposes cluster-based mention typing for named entity disambiguation. The aim of mention typing is to predict the type of a given mention based on its context. Generally, manually curated type taxonomies such as Wikipedia categories are used. We introduce cluster-based mention typing, where named entities are clustered based on their contextual similarities and the cluster ids are assigned as types. The hyperlinked mentions and their context in Wikipedia are used in order to obtain these cluster-based types. Then, mention typing models are trained on these mentions, which have been labeled with their cluster-based types through distant supervision. At the named entity disambiguation phase, first the cluster-based types of a given mention are predicted and then, these types are used as features in a ranking model to select the best entity among the candidates. We represent entities at multiple contextual levels and obtain different clusterings (and thus typing models) based on each level. As each clustering breaks the entity space differently, mention typing based on each clustering discriminates the mention differently. When predictions from all typing models are used together, our system achieves better or comparable results based on randomization tests with respect to the state-of-the-art levels on four defacto test sets.

Biochemical methods that measure affinity and biophysical methods that describe the interaction in atomistic level detail have provided valuable information toward a mechanistic explanation for bimolecular recognition [1]. However, more often than not, compounds with drug potential are discovered serendipitously or by phenotypic drug discovery [2] since this highly specific interaction is still difficult to predict [3]. Protein structure based computational strategies such as docking [4], ultra-large library docking for discovering new chemotypes [5], and molecular dynamics simulations [4] or ligand based strategies such as quantitative structure-activity relationship (QSAR) [6, 7], and molecular similarity [8] have been powerful at narrowing down the list of compounds to be tested experimentally. With the increase in available data, machine learning and deep learning architectures are also starting to play a significant role in cheminformatics and drug discovery [9]. These approaches often require extensive computational resources or they are limited by the availability of 3D information. On the other hand, text based representations of biochemical entities are more readily available as evidenced by the 19,588 biomolecular complexes (3D structures) in PDB-Bind [10] (accessed on Nov 13, 2019) compared with 561,356 (manually annotated and reviewed) protein sequences in Uniprot [11] (accessed on Nov 13, 2019) or 97 million compounds in Pubchem [12] (accessed on Nov 13, 2019). The advances in natural language processing (NLP) methodologies make processing of text based representations of biomolecules an area of intense research interest. The discipline of natural language processing (NLP) comprises a variety of methods that explore a large amount of textual data in order to bring unstructured, latent (or hidden) knowledge to the fore [13]. Advances in this field are beneficial for tasks that use language (textual data) to build insight.

Motivation: Prediction of the interaction affinity between proteins and compounds is a major challenge in the drug discovery process. WideDTA is a deep-learning based prediction model that employs chemical and biological textual sequence information to predict binding affinity. Results: WideDTA uses four text-based information sources, namely the protein sequence, ligand SMILES, protein domains and motifs, and maximum common substructure words to predict binding affinity. WideDTA outperformed one of the state of the art deep learning methods for drug-target binding affinity prediction, DeepDTA on the KIBA dataset with a statistical significance. This indicates that the word-based sequence representation adapted by WideDTA is a promising alternative to the character-based sequence representation approach in deep learning models for binding affinity prediction, such as the one used in DeepDTA. In addition, the results showed that, given the protein sequence and ligand SMILES, the inclusion of protein domain and motif information as well as ligand maximum common substructure words do not provide additional useful information for the deep learning model. Interestingly, however, using only domain and motif information to represent proteins achieved similar performance to using the full protein sequence, suggesting that important binding relevant information is contained within the protein motifs and domains.

Identification of high affinity drug-target interactions (DTI) is a major research question in drug discovery. In this study, we propose a novel methodology to predict drug-target binding affinity using only ligand SMILES information. We represent proteins using the word-embeddings of the SMILES representations of their strong binding ligands. Each SMILES is represented in the form of a set of chemical words and a protein is described by the set of chemical words with the highest Term Frequency- Inverse Document Frequency (TF-IDF) value. We then utilize the Support Vector Regression (SVR) algorithm to predict protein - drug binding affinities in the Davis and KIBA Kinase datasets. We also compared the performance of SMILES representation with the recently proposed DeepSMILES representation and found that using DeepSMILES yields better performance in the prediction task. Using only SMILESVec, which is a strictly string based representation of the proteins based on their interacting ligands, we were able to predict drug-target binding affinity as well as or better than the KronRLS or SimBoost models that utilize protein sequence.