Gökçe Uludoğan

Gökçe Uludoğan, Elif Ozkirimli, Kutlu O. Ulgen et al.

Motivation: The development of novel compounds targeting proteins of interest is one of the most important tasks in the pharmaceutical industry. Deep generative models have been applied to targeted molecular design and have shown promising results. Recently, target-specific molecule generation has been viewed as a translation between the protein language and the chemical language. However, such a model is limited by the availability of interacting protein-ligand pairs. On the other hand, large amounts of unlabeled protein sequences and chemical compounds are available and have been used to train language models that learn useful representations. In this study, we propose exploiting pretrained biochemical language models to initialize (i.e. warm start) targeted molecule generation models. We investigate two warm start strategies: (i) a one-stage strategy where the initialized model is trained on targeted molecule generation (ii) a two-stage strategy containing a pre-finetuning on molecular generation followed by target specific training. We also compare two decoding strategies to generate compounds: beam search and sampling. Results: The results show that the warm-started models perform better than a baseline model trained from scratch. The two proposed warm-start strategies achieve similar results to each other with respect to widely used metrics from benchmarks. However, docking evaluation of the generated compounds for a number of novel proteins suggests that the one-stage strategy generalizes better than the two-stage strategy. Additionally, we observe that beam search outperforms sampling in both docking evaluation and benchmark metrics for assessing compound quality. Availability and implementation: The source code is available at https://github.com/boun-tabi/biochemical-lms-for-drug-design and the materials are archived in Zenodo at https://doi.org/10.5281/zenodo.6832145

Gökçe Uludoğan, Buse Giledereli, Elif Ozkirimli et al.

Proteins carry out biological functions through the coordinated action of groups of residues organized into structural arrangements. These arrangements, which we refer to as protein units, exist at an intermediate scale, being larger than individual residues yet smaller than entire proteins. A deeper understanding of protein function can be achieved by identifying these units and their associations with function. However, existing approaches either focus on residue-level signals, rely on curated annotations, or segment protein structures without incorporating functional information, thereby limiting interpretable analysis of structure-function relationships. We introduce PUFFIN, a data-driven framework for discovering protein units by jointly learning structural partitioning and functional supervision. PUFFIN represents proteins as residue-level structure graphs and applies a graph neural network with a structure-aware pooling mechanism that partitions each protein into multi-residue units, with functional supervision that shapes the partition. We show that the learned units are structurally coherent, exhibit organized associations with molecular function, and show meaningful correspondence with curated InterPro annotations. Together, these results demonstrate that PUFFIN provides an interpretable framework for analyzing structure-function relationships using learned protein units and their statistical function associations. We made our source code available at https://github.com/boun-tabi-lifelu/puffin.

Mehmet Efe Akça, Gökçe Uludoğan, Arzucan Özgür et al.

Accurate prediction of protein function is essential for elucidating molecular mechanisms and advancing biological and therapeutic discovery. Yet experimental annotation lags far behind the rapid growth of protein sequence data. Computational approaches address this gap by associating proteins with Gene Ontology (GO) terms, which encode functional knowledge through hierarchical relations and textual definitions. However, existing models often emphasize one modality over the other, limiting their ability to generalize, particularly to unseen or newly introduced GO terms that frequently arise as the ontology evolves, and making the previously trained models outdated. We present STAR-GO, a Transformer-based framework that jointly models the semantic and structural characteristics of GO terms to enhance zero-shot protein function prediction. STAR-GO integrates textual definitions with ontology graph structure to learn unified GO representations, which are processed in hierarchical order to propagate information from general to specific terms. These representations are then aligned with protein sequence embeddings to capture sequence-function relationships. STAR-GO achieves state-of-the-art performance and superior zero-shot generalization, demonstrating the utility of integrating semantics and structure for robust and adaptable protein function prediction. Code is available at https://github.com/boun-tabi-lifelu/stargo.

Gökçe Uludoğan, Zeynep Yirmibeşoğlu Balal, Furkan Akkurt et al.

The recent advances in natural language processing have predominantly favored well-resourced English-centric models, resulting in a significant gap with low-resource languages. In this work, we introduce the language model TURNA, which is developed for the low-resource language Turkish and is capable of both natural language understanding and generation tasks. TURNA is pretrained with an encoder-decoder architecture based on the unified framework UL2 with a diverse corpus that we specifically curated for this purpose. We evaluated TURNA with three generation tasks and five understanding tasks for Turkish. The results show that TURNA outperforms several multilingual models in both understanding and generation tasks, and competes with monolingual Turkish models in understanding tasks. TURNA is made available at https://huggingface.co/boun-tabi-LMG/TURNA .

Somaiyeh Dehghan, Gökçe Uludoğan, Mehmet Umut Şen et al.

Online hate speech has been linked to a global rise in violence against minorities, including incidents such as mass shootings, lynchings, and ethnic cleansing. Societies grappling with this issue, particularly when hate speech targets specific groups based on religion, race, ethnicity, culture, nationality, or migration status, face the challenge of balancing freedom of expression with the need for effective content moderation on widely used online platforms. In response to this challenge, we introduce a comprehensive hate speech dataset covering five distinct topics in Turkish: refugees, the Israel-Palestine conflict, anti-Greek sentiment in Turkey, ethnic or religious communities (Alevis, Armenians, Arabs, Jews, and Kurds), and LGBTI+, alongside one topic in Arabic (refugees). In addition, we develop state-of-the-art BERT-based models to address multiple dimensions of hate speech analysis, including hate category classification, hate intensity prediction, target identification, and hate speech span detection, enabling a comprehensive understanding of hateful content in online discourse.