Biology subjects

Ilie, L.

Publications and source records attributed to Ilie, L..

5 recordsLinked to original sources

bioRxiv2025

Ankh-score produces better sequence alignments than AlphaFold3

Protein sequence alignment is one of the most fundamental procedures in bioinformatics. Due to its many downstream applications, improvements to this procedure are of great importance. We consider two revolutionary con-cepts that emerged recently as candidates for improving the state-of-the-art alignment methods: AlphaFold and protein language models such as Ankh, ProtT5 or ESM-C. Alignment improvements can come from the structural alignment of AlphaFold-predicted structures or the scoring based on the similarity of protein embeddings produced by the protein language models. Thorough comparison on many domains from BAliBASE and CDD demonstrates that the Ankh-score method produces much better sequence alignments than the structural alignments using US-align of AlphaFold3-predicted structures. Both are better than the traditional method using BLOSUM matrices. This suggests that Ankh embeddings may possess certain information that is not available in the AlphaFold3-predicted structures. The alignment software is freely available as a web server at e-score.csd.uwo.ca and as source code at github.com/lucian-ilie/E-score.

bioinformatics↗

bioRxiv2025

C3PI: Component Puzzle Protein-Protein Interaction Prediction

Proteins primarily perform their functions through interactions with other proteins, making the accurate prediction of protein-protein interactions (PPIs) a fundamental problem. Experimental methods for determining PPIs are often slow and expensive, which has driven significant efforts to improve the performance of computational methods in this field. While many methods have been designed, recent thorough investigations proved that the existing methods learn exclusively from sequence similarities and node degrees. When such data leakage is avoided, performances were shown to become random. We introduce C3PI, a novel sequence-based deep learning framework designed for predicting PPIs. C3PI uses as input ProtT5 protein embeddings into a complex architecture that includes two novel components, a puzzler and an entangler, which significantly enhance the models performance. Through extensive comparisons with state-of-the-art methods across many datasets, C3PI consistently outperforms competing approaches, especially in key metrics such as AUPRC and AUROC. Most importantly, C3PI is the first PPI prediction method to achieve a significant improvement over random on the leakage-free gold standard dataset. C3PI is available as a web server at c3pi.csd.uwo.ca and source code from github.com/lucian-ilie/C3PI.

bioinformatics↗

bioRxiv2025

Protein Embeddings and Local Alignments

BackgroundThe advent of protein embeddings has revolutionized bioinformatics by providing contextual representations that capture functional and evolutionary patterns. They have become, alongside sequence alignments, the cornerstone of bioinformatics. While embeddings cannot replace alignments, they can greatly help improving their quality. Our goal is replacing the BLOSUM matrices, the decades-old standard scoring system for protein alignment, with an embedding-based scoring method. ResultsWe introduce a new scoring function and algorithm for local alignment of protein sequences, we offer a new comprehensive framework for evaluating local alignments. The score between two residues is given by the cosine similarity of their Ankh-embedding vectors and the algorithm uses dynamic programming with affine penalty. For the evaluation, we built multiple datasets, using both natural and inserted sequences, from the Conserved Domain Database, BAL-iBASE, and GPCRdb, designed a new algorithm for local alignment extraction, localization and quality evaluation, and employed five distance metrics to evaluate the similarity with the true alignment. We performed nearly one and a half million tests to compare the new algorithm with the best BLOSUM matrices, specialized GPCRtm matrices, and top programs, such as PEbA, ProtT5-score, DEDAL, vcMSA and pLM-BLAST. Regarding the protein embedding models, Ankh not only surpasses the best combination of ProtT5 and ESM2, but appears to better understand the "language" of proteins, as it behaves much better on natural sequences compared to artificial ones obtained by inserting domains in random protein sequences. Also, while ProtT5 and ESM2 combine to produce better results, Ankh does not combine well with other embeddings. ConclusionsThe new Ankh-score-based program is vastly superior to the BLOSUM matrices and clearly superior to all existing methods. New light shed on the protein embeddings can guide future improvements. In order to facilitate the use of the new method and protocol, they are freely available as a web server at e-score.csd.uwo.ca and as source code at github.com/lucian-ilie/E-score.

bioinformatics↗

bioRxiv2023

Seq-InSite: sequence supersedes structure for protein interaction site prediction

Proteins accomplish cellular functions by interacting with each other, which makes the prediction of interaction sites a fundamental problem. Computational prediction of the interaction sites has been studied extensively, with the structure-based programs being the most accurate, while the sequence-based ones being much more widely applicable, as the sequences available outnumber the structures by two orders of magnitude. We provide here the first solution that achieves both goals. Our new sequence-based program, Seq-InSite, greatly surpasses the performance of sequence-based models, matching the quality of state-of-the-art structure-based predictors, thus effectively superseding the need for models requiring structure. Seq-InSite is illustrated using an analysis of four protein sequences. Seq-InSite is freely available as a web server at seq-insite.csd.uwo.ca and as free source code, including trained models and all datasets used for training and testing, at github.com/lucian-ilie/seq-insite.

bioinformatics↗

bioRxiv2020

DELPHI: accurate deep ensemble model for protein interaction sites prediction

MotivationProteins usually perform their functions by interacting with other proteins, which is why accurately predicting protein-protein interaction (PPI) binding sites is a fundamental problem. Experimental methods are slow and expensive. Therefore, great efforts are being made towards increasing the performance of computational methods. ResultsWe propose DELPHI (DEep Learning Prediction of Highly probable protein Interaction sites), a new sequence-based deep learning suite for PPI binding sites prediction. DELPHI has an ensemble structure with data augmentation and it employs novel features in addition to existing ones. We comprehensively compare DELPHI to nine state-of-the-art programs on five datasets and show that it is more accurate. AvailabilityThe trained model, source code for training, predicting, and data processing are freely available at https://github.com/lucian-ilie/DELPHI. All datasets used in this study can be downloaded at http://www.csd.uwo.ca/~ilie/DELPHI/. Contactilie@uwo.ca

bioinformatics↗