Computational deconvolution of the dengue immune response complexity with  identification of novel broadly neutralizing antibodies

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.

Schlagwörter

Fachgebiet (DDC)

Projekt

Veranstaltung

Postdoc Network Meeting

Startdatum der Ausstellung

Enddatum der Ausstellung

Startdatum der Konferenz

21.09.2022

Enddatum der Konferenz

23.09.2022

Datum der letzten Prüfung

ISBN

ISSN

Sprache

Englisch

Während FHNW Zugehörigkeit erstellt

Ja

Zukunftsfelder FHNW

Publikationsstatus

Begutachtung

Keine Begutachtung

Open Access-Status

Lizenz

Zitation

Natali, E. N., Horst, A., Meier, P., Greiff, V., Nuvolone, M., Babrak, L. M., Djordjevic, K., Fink, K., Traggiai, E., & Miho, E. (2022, September 21). Computational deconvolution of the dengue immune response complexity with identification of novel broadly neutralizing antibodies. Postdoc Network Meeting. https://doi.org/10.26041/fhnw-9932

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