Khan, I. U. | Search bioRxiv

bioRxiv2025

Improved Graph-based Antibody-aware Epitope Prediction with Protein Language Model-based Embeddings

The accurate identification of B-cell epitopes is critical in antibody design, diagnostics, and immunotherapies. Many in silico approaches have recently been proposed to predict epitopes, but these approaches struggle primarily because of the variational and conformational nature of epitopes. However, deep learning-based approaches have recently shown great promise in achieving better performance at the epitope prediction task. In this paper, we employ a graph convolutional network (GCN) coupled with pre-trained protein language model (PLM)-based embeddings for epitope prediction on a benchmark antibody-specific epitope prediction (AsEP) dataset. We explore the use of different PLM-embedding methods on the epitope prediction task and show that the choice of PLM embeddings impacts the performance. Specifically, we find that antibody-specific PLMs such as AntiBERTy and general PLMs such as ProtTrans and ESM-2 for antigens provide improved epitope prediction performance with an AUCROC of 0.65, precision of 0.28, and recall of 0.46. The source code is available at: https://github.com/mansoor181/walle-pp.git.

bioinformatics↗

bioRxiv2024

Preserving Hidden Hierarchical Structure: Poincare Distance for Enhanced Genomic Sequence Analysis

The analysis of large volumes of molecular (genomic, proteomic, etc.) sequences has become a significant research field, especially after the recent coronavirus pandemic. Although it has proven beneficial to sequence analysis, machine learning (ML) is not without its difficulties, particularly when the feature space becomes highly dimensional. While most ML models operate with the conventional Euclidean distance, the hidden hierarchical structure present among a set of phylogenetically related sequences is difficult to represent in Euclidean space without losing much information or requiring many dimensions. Since such hierarchical structure can be informative to analysis tasks such as clustering and classification, we propose two measures for generating a distance matrix from a set of sequences based on distance in the Poincare disk model of hyperbolic geometry, or the Poincare distance, for short. Such a distance measure can allow to embedding of even a fully resolved phylogenetic tree in just two dimensions with minimal distortion to any hierarchical structure. Our first approach is based purely on the classical Poincare distance, while the other approach modifies this distance by combining the Euclidean norms and the dot product between the sequence representations. A thorough analysis of both measures demonstrates its superiority in a variety of genomic and proteomic sequence classification tasks in terms of efficiency, accuracy, predictive performance, and the capacity to capture significant sequence correlations. These approaches perform better than existing state-of-the-art methods across the majority of evaluation metrics.

genomics↗