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Biology subjects

Georgievska, S.

Publications and source records attributed to Georgievska, S..

3 recordsLinked to original sources

sv-channels: filtering genomic deletions using one-dimensional convolutional neural networks

Structural variant (SV) detection in human genomes using short-read sequencing data is hindered by false positives, arising from sequencing and mapping artifacts that mimic genuine SV signals. Despite advances, state-of-the-art SV callers like GRIDSS and Manta exhibit trade-offs between precision and recall, with GRIDSS offering the highest precision and Manta excelling in recall. To address these limitations, we introduce sv-channels, a novel deep learning model designed to improve the precision of SV detection by leveraging read information at call sites. Our method effectively reduces false positives in Mantas deletion callsets, achieving precision that surpasses GRIDSS while maintaining a recall rate comparable to Manta. This represents a significant improvement in SV detection, leveraging Mantas high recall through deep learning and paving the way for more accurate genomic analyses. The sv-channels codebase is openly accessible on GitHub at https://github.com/GooglingTheCancerGenome/sv-channels enabling further research and application in the field.

bioinformatics↗

Improving generalizability for MHC-binding peptide predictions through structure-based geometric deep learning

The interaction between peptides and major histocompatibility complex (MHC) molecules is pivotal in autoimmunity, pathogen recognition and tumor immunity. Recent advances in cancer immunotherapies demand for more accurate computational prediction of MHC-bound peptides. We address the generalizability challenge of MHC-bound peptide predictions, revealing limitations in current sequence-based approaches. Our structure-based methods leveraging geometric deep learning (GDL) demonstrated promising improvement in generalizability across unseen MHC alleles. Further, we tackle data efficiency by introducing a self-supervised learning approach on structures (3D-SSL). Without being exposed to any binding affinity data, our 3D-SSL outperforms sequence-based methods trained on [~]90 times more datapoints. Finally, we demonstrate the resilience of structure-based GDL methods to biases in binding data on an Hepatitis B virus vaccine immunopeptidomics case study. This proof-of-concept study highlights structure-based methods potential to enhance generalizability and data efficiency, with important implications for data-intensive fields like T-cell receptor specificity predictions, paving the way for enhanced comprehension and manipulation of immune responses.

bioinformatics↗

DeepRank: A deep learning framework for data mining 3D protein-protein interfaces

Three-dimensional (3D) structures of protein complexes provide fundamental information to decipher biological processes at the molecular scale. The vast amount of experimentally and computationally resolved protein-protein interfaces (PPIs) offers the possibility of training deep learning models to aid the predictions of their biological relevance. We present here DeepRank, a general, configurable deep learning framework for data mining PPIs using 3D convolutional neural networks (CNNs). DeepRank maps features of PPIs onto 3D grids and trains a user-specified CNN on these 3D grids. DeepRank allows for efficient training of 3D CNNs with data sets containing millions of PPIs and supports both classification and regression. We demonstrate the performance of DeepRank on two distinct challenges: The classification of biological versus crystallographic PPIs, and the ranking of docking models. For both problems DeepRank is competitive or outperforms state-of-the-art methods, demonstrating the versatility of the framework for research in structural biology.

bioinformatics↗