Auflistung nach Autor:in "Horst, Alexander"

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Author Correction. The dengue-specific immune response and antibody identification with machine learning
(Nature, 20.01.2024) Natali, Eriberto Noel; Horst, Alexander; Meier, Patrick; Greiff, Victor; Nuvolone, Mario; Babrak, Lmar Marie; Fink, Katja; Miho, Enkelejda
Dengue virus poses a serious threat to global health and there is no specific therapeutic for it. Broadly neutralizing antibodies recognizing all serotypes may be an effective treatment. High-throughput adaptive immune receptor repertoire sequencing (AIRR-seq) and bioinformatic analysis enable in-depth understanding of the B-cell immune response. Here, we investigate the dengue antibody response with these technologies and apply machine learning to identify rare and underrepresented broadly neutralizing antibody sequences. Dengue immunization elicited the following signatures on the antibody repertoire: (i) an increase of CDR3 and germline gene diversity; (ii) a change in the antibody repertoire architecture by eliciting power-law network distributions and CDR3 enrichment in polar amino acids; (iii) an increase in the expression of JNK/Fos transcription factors and ribosomal proteins. Furthermore, we demonstrate the applicability of computational methods and machine learning to AIRR-seq datasets for neutralizing antibody candidate sequence identification. Antibody expression and functional assays have validated the obtained results.
01A - Beitrag in wissenschaftlicher Zeitschrift
Computational deconvolution of the dengue immune response complexity with identification of novel broadly neutralizing antibodies
(21.09.2022) Natali, Eriberto Noel; Horst, Alexander; Meier, Patrick; Greiff, Victor; Nuvolone, Mario; Babrak, Lmar Marie; Djordjevic, Kristina; Fink, Katja; Traggiai, Elisabetta; Miho, Enkelejda
Dengue virus poses a serious threat to global health as the causative agent of the dengue fever. Currently, there is no approved therapeutic, and broadly neutralizing antibodies recognizing all four serotypes may be an effective treatment. High-throughput immune repertoire sequencing and bioinformatic analysis enable in-depth understanding of the immune response in dengue infection. Here, we use these technologies and apply machine learning to identify rare and underrepresented broadly neutralizing antibody sequences through investigation of antibody response in dengue. We observed challenging the immune system with dengue elicits the following signatures on the antibody repertoire: (i) an increase of the diversity in the CDR3 regions and the germline genes; (ii) a change in the architecture by eliciting power-law network distributions and enrichment in polar amino acids of the CDR3; (iii) an increase in the expression of transcription factors of the JNK/Fos pathways and ribosomal proteins. Moreover, our work demonstrates the applicability of computational methods and machine learning to high-throughput antibody repertoire sequencing datasets for neutralizing antibody candidate identification. Further investigation with antibody expression and functional assays is planned to validate the obtained results.
06 - Präsentation
Machine learning detects anti-DENV signatures in antibody repertoire sequences
(Frontiers, 11.10.2021) Horst, Alexander; Smakaj, Erand; Natali, Eriberto; Tosoni, Deniz David; Babrak, Lmar; Meier, Patrick; Miho, Enkelejda
Dengue infection is a global threat. As of today, there is no universal dengue fever treatment or vaccines unreservedly recommended by the World Health Organization. The investigation of the specific immune response to dengue virus would support antibody discovery as therapeutics for passive immunization and vaccine design. High-throughput sequencing enables the identification of the multitude of antibodies elicited in response to dengue infection at the sequence level. Artificial intelligence can mine the complex data generated and has the potential to uncover patterns in entire antibody repertoires and detect signatures distinctive of single virus-binding antibodies. However, these machine learning have not been harnessed to determine the immune response to dengue virus. In order to enable the application of machine learning, we have benchmarked existing methods for encoding biological and chemical knowledge as inputs and have investigated novel encoding techniques. We have applied different machine learning methods such as neural networks, random forests, and support vector machines and have investigated the parameter space to determine best performing algorithms for the detection and prediction of antibody patterns at the repertoire and antibody sequence levels in dengue-infected individuals. Our results show that immune response signatures to dengue are detectable both at the antibody repertoire and at the antibody sequence levels. By combining machine learning with phylogenies and network analysis, we generated novel sequences that present dengue-binding specific signatures. These results might aid further antibody discovery and support vaccine design.
01A - Beitrag in wissenschaftlicher Zeitschrift
Machine Learning-based Analysis of Sequenced Antibodies to Determine Broadly Neutralizing anti-DENV Antibodies
(Hochschule für Wirtschaft FHNW, 2020) Horst, Alexander; Miho, Enkelejda
Background: The dengue virus is a global threat to public health as roughly half of the world's population is living in a risk area and as of today, there is no vaccine for disease prevention against all dengue serotypes (WHO, 2019). Advancements in high throughput sequencing enable efficient analysis of human immune repertoire data to obtain more insights about the immune disease. As the complexity of sequencing data is very high, artificial intelligence-based analysis could help overcome this complexity and ultimately lead to the identification of broadly neutralizing antibodies against the dengue virus. Methods: Various supervised machine learning (ML) methods were trained with publicly available sequencing datasets of serotype-specific, dengue-challenged individuals. Additionally, a control group of sequences from non-immunized healthy individuals was used (repertoire-level classification, Godoy-Lozano et al., 2016; Huang et al., 2017; Parameswaranet al., 2013). Besides considering different machine learning architectures, various encoding methods were taken into consideration and a novel physicochemical properties-based encoding method was introduced. Subsequently, similarity networks were used to justify the predictions before the models were trained to classify whether single antibodies could potentially bind to dengue antigens or not (sequence-level classification)....
11 - Studentische Arbeit
The dengue-specific immune response and antibody identification with machine learning
(Nature, 20.01.2024) Natali, Eriberto Noel; Horst, Alexander; Meier, Patrick; Greiff, Victor; Nuvolone, Mario; Babrak, Lmar Marie; Fink, Katja; Miho, Enkelejda
Dengue virus poses a serious threat to global health and there is no specific therapeutic for it. Broadly neutralizing antibodies recognizing all serotypes may be an effective treatment. High-throughput adaptive immune receptor repertoire sequencing (AIRR-seq) and bioinformatic analysis enable in-depth understanding of the B-cell immune response. Here, we investigate the dengue antibody response with these technologies and apply machine learning to identify rare and underrepresented broadly neutralizing antibody sequences. Dengue immunization elicited the following signatures on the antibody repertoire: (i) an increase of CDR3 and germline gene diversity; (ii) a change in the antibody repertoire architecture by eliciting power-law network distributions and CDR3 enrichment in polar amino acids; (iii) an increase in the expression of JNK/Fos transcription factors and ribosomal proteins. Furthermore, we demonstrate the applicability of computational methods and machine learning to AIRR-seq datasets for neutralizing antibody candidate sequence identification. Antibody expression and functional assays have validated the obtained results.
01A - Beitrag in wissenschaftlicher Zeitschrift
Virtual bartender: a dialog system combining data-driven and knowledge-based recommendation
(2019) Hinkelmann, Knut; Blaser, Monika; Faust, Oliver; Horst, Alexander; Mehli, Carlo; Martin, Andreas; Hinkelmann, Knut; Gerber, Aurona; Lenat, Doug; van Harmelen, Frank; Clark, Peter
This research is about combination of data-driven and knowledge-based recommendations The research is made in an application scenario for whisky recommendation, where a guest chats with a recommender system. Preferences about taste are difficult to express and the knowledge about taste is tacit and thus can hardly be represented and used adequately. People or not aware of how to describe flavors in a standardized way and how to do a justified choice. This is because knowledge about taste is mainly tacit knowledge. To deal with this knowledge, data-driven recommendation is adequate. On the other hand, in particular experienced customers use knowledge about distilleries, locations and the distillery process to express their preferences and want to have arguments for the recommended products. This shows that a combination of data-driven and knowledge-based recommendations is appropriate in areas where tacit knowledge and explicit knowledge are available.
04B - Beitrag Konferenzschrift