Auflistung nach Autor:in "Traggiai, Elisabetta"

Gerade angezeigt 1 - 3 von 3

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
Synthetic standards combined with error and bias correction improve the accuracy and quantitative resolution of antibody repertoire sequencing in human naïve and memory B cells
(Frontiers Research Foundation, 20.06.2018) Friedensohn, Simon; Lindner, John M.; Cornacchione, Vanessa; Iazeolla, Mariavittoria; Miho, Enkelejda; Zingg, Andreas; Meng, Simon; Traggiai, Elisabetta; Reddy, Sai T.
High-throughput sequencing of immunoglobulin (Ig) repertoires (Ig-seq) is a powerful method for quantitatively interrogating B cell receptor sequence diversity. When applied to human repertoires, Ig-seq provides insight into fundamental immunological questions, and can be implemented in diagnostic and drug discovery projects. However, a major challenge in Ig-seq is ensuring accuracy, as library preparation protocols and sequencing platforms can introduce substantial errors and bias that compromise immunological interpretation. Here, we have established an approach for performing highly accurate human Ig-seq by combining synthetic standards with a comprehensive error and bias correction pipeline. First, we designed a set of 85 synthetic antibody heavy-chain standards (in vitro transcribed RNA) to assess correction workflow fidelity. Next, we adapted a library preparation protocol that incorporates unique molecular identifiers (UIDs) for error and bias correction which, when applied to the synthetic standards, resulted in highly accurate data. Finally, we performed Ig-seq on purified human circulating B cell subsets (naïve and memory), combined with a cellular replicate sampling strategy. This strategy enabled robust and reliable estimation of key repertoire features such as clonotype diversity, germline segment, and isotype subclass usage, and somatic hypermutation. We anticipate that our standards and error and bias correction pipeline will become a valuable tool for researchers to validate and improve accuracy in human Ig-seq studies, thus leading to potentially new insights and applications in human antibody repertoire profiling.
01A - Beitrag in wissenschaftlicher Zeitschrift
Synthetic standards combined with error and bias correction improve the accuracy and quantitative resolution of antibody repertoire sequencing in human naïve and memory B cells
(Frontiers Research Foundation, 20.06.2018) Friedensohn, Simon; Lindner, John M.; Cornacchione, Vanessa; Iazeolla, Mariavittoria; Miho, Enkelejda; Zingg, Andreas; Meng, Simon; Traggiai, Elisabetta; Reddy, Sai T.
High-throughput sequencing of immunoglobulin (Ig) repertoires (Ig-seq) is a powerful method for quantitatively interrogating B cell receptor sequence diversity. When applied to human repertoires, Ig-seq provides insight into fundamental immunological questions, and can be implemented in diagnostic and drug discovery projects. However, a major challenge in Ig-seq is ensuring accuracy, as library preparation protocols and sequencing platforms can introduce substantial errors and bias that compromise immunological interpretation. Here, we have established an approach for performing highly accurate human Ig-seq by combining synthetic standards with a comprehensive error and bias correction pipeline. First, we designed a set of 85 synthetic antibody heavy-chain standards (in vitro transcribed RNA) to assess correction workflow fidelity. Next, we adapted a library preparation protocol that incorporates unique molecular identifiers (UIDs) for error and bias correction which, when applied to the synthetic standards, resulted in highly accurate data. Finally, we performed Ig-seq on purified human circulating B cell subsets (naïve and memory), combined with a cellular replicate sampling strategy. This strategy enabled robust and reliable estimation of key repertoire features such as clonotype diversity, germline segment, and isotype subclass usage, and somatic hypermutation. We anticipate that our standards and error and bias correction pipeline will become a valuable tool for researchers to validate and improve accuracy in human Ig-seq studies, thus leading to potentially new insights and applications in human antibody repertoire profiling.
01A - Beitrag in wissenschaftlicher Zeitschrift