On AIRR 15: Germline databases or adventures into the allelic underworld with Dr. Corey Watson and Dr. William Lees

Dr. Corey Watson is an Associate Professor at the University of Louisville. His work focuses on characterising and cataloguing antibody genetic diversity in human and mouse to better understand disease susceptibility and clinical health outcomes. Dr. William Lees is a researcher at University of London. His work focuses on developing Adaptive Immune Receptor (AIR) reference sets for diverse species and the annotation of experimental sequence data. In this episode we talk about the recent work by the Germline Database Working Group of the AIRR-Community. The accuracy of V and J gene segment assignment improves with the quality of the reference germline set. The accurate assignment is critical for characterization of somatic hypermutation. We discuss the challenges in creating a database to hold all relevant and potentially relevant germline information, especially in the light of increased discovery rate through technological advances and improved analysis pipelines. We also reflect on the complexity in handling personalised germline reference sets. The episode is hosted by Dr. Ulrik Stervbo and Dr. Zhaoqing Ding. Comments are welcome to the inbox of [email protected]  or on social media under the tag #onAIRR. Further information can be found here: https://www.antibodysociety.org/the-airr-community/airr-c-podcast.  Website of the AIRR-C Germline Database Working Group https://www.antibodysociety.org/the-airr-community/airr-working-groups/germline_database/  Papers mentioned Collins, Andrew M., Mats Ohlin, Martin Corcoran, James M. Heather, Duncan Ralph, Mansun Law, Jesus Martínez-Barnetche, et al. 2023. “AIRR-C Human IG Reference Sets: Curated Sets of Immunoglobulin Heavy and Light Chain Germline Genes.” BioRxiv. https://doi.org/10.1101/2023.09.01.555348  Rodriguez, Oscar L., Yana Safonova, Catherine A. Silver, Kaitlyn Shields, William S. Gibson, Justin T. Kos, David Tieri, et al. 2023. “Genetic Variation in the Immunoglobulin Heavy Chain Locus Shapes the Human Antibody Repertoire.” Nature Communications 14 (1). https://doi.org/10.1038/s41467-023-40070-x  Lees, William D., Scott Christley, Ayelet Peres, Justin T. Kos, Brian Corrie, Duncan Ralph, Felix Breden, et al. 2023. “AIRR Community Curation and Standardised Representation for Immunoglobulin and T Cell Receptor Germline Sets.” Immunoinformatics (Amsterdam, Netherlands) 10 (100025): 100025. https://doi.org/10.1016/j.immuno.2023.100025  Jackson, Katherine J. L., Justin T. Kos, William Lees, William S. Gibson, Melissa Laird Smith, Ayelet Peres, Gur Yaari, et al. 2022. “A BALB/c IGHV Reference Set, Defined by Haplotype Analysis of Long-Read VDJ-C Sequences From F1 (BALB/c x C57BL/6) Mice.” Frontiers in Immunology 13. https://doi.org/10.3389/fimmu.2022.888555  Ford, Easton E., David Tieri, Oscar L. Rodriguez, Nancy J. Francoeur, Juan Soto, Justin T. Kos, Ayelet Peres, et al. 2023. “FLAIRR-Seq: A Method for Single-Molecule Resolution of near Full-Length Antibody H Chain Repertoires.” The Journal of Immunology 210 (10): 1607–19. https://doi.org/10.4049/jimmunol.2200825  Omer, Aviv, Ayelet Peres, Oscar L. Rodriguez, Corey T. Watson, William Lees, Pazit Polak, Andrew M. Collins, and Gur Yaari. 2022. “T Cell Receptor Beta Germline Variability Is Revealed by Inference from Repertoire Data.” Genome Medicine 14 (1). https://doi.org/10.1186/s13073-021-01008-4  Rodriguez, Oscar L., Catherine A. Silver, Kaitlyn Shields, Melissa L. Smith, and Corey T. Watson. 2022. “Targeted Long-Read Sequencing Facilitates Phased Diploid Assembly and Genotyping of the Human T Cell Receptor Alpha, Delta, and Beta Loci.” Cell Genomics 2 (12): 100228. https://doi.org/10.1016/j.xgen.2022.100228  Tools mentioned TIgGER (Immcantation) https://tigger.readthedocs.io/en/stable  IgDiscover https://github.com/NBISweden/IgDiscover  Partis https://github.com/psathyrella/partis MiXCR https://mixcr.com

Alexander Bernier BCL, JD, LLM, SJD (Candidate) is a Montreal-based lawyer, and a doctoral candidate at the University of Toronto Faculty of Law. His work aims to give scientists a range of compliant data sharing designs that scientists can implement in different situations. In this episode, we discuss the risk of identifying individuals in a biological data set, how this is approached differently in different countries, and possible strategies to ensure data privacy. The episode is hosted by Dr. Ulrik Stervbo and Dr. Zhaoqing Ding. Comments are welcome to the inbox of [email protected]  or on social media under the tag #onAIRR. Further information can be found here: https://www.antibodysociety.org/the-airr-community/airr-c-podcast. 

Maxim Zaslavsky is a computer scientist using machine learning to address problems in immunology. He is currently PhD student at Stanford University. Scott D. Boyd is a physician-scientist and Professor of Pathology and of Food Allergy and Immunology at Stanford University. His group is focused on using high-throughput DNA sequencing and single-cell experiments to analyse human immune responses to infection and vaccination. We discuss the preprint “Disease diagnostics using machine learning of immune receptors”, available at BioRxiv: https://doi.org/10.1101/2022.04.26.489314. The work is led by Maxim Zaslavsky with Scott Boyd the corresponding author. In the manuscript, the authors demonstrate how AIRR-seq and machine learning can be used in disease diagnostics. The episode is hosted by Dr. Ulrik Stervbo and Dr. Zhaoqing Ding. Comments are welcome to the inbox of [email protected]  or on social media under the tag #onAIRR. Further information can be found here: https://www.antibodysociety.org/the-airr-community/airr-c-podcast.

Dr. Charlotte Deane is Professor of Structural Bioinformatics in the Department of Statistics in University of Oxford (UK) and heads the Oxford Protein Informatics Group. Prof. Deane’s research merges statistics, immunoinformatics, protein structure and small molecule drug discovery. Her group has published several databases that are widely used by academic researchers and in pharmaceutical drug discovery pipelines. We discuss the relevance of including protein structure to study and design antibodies, and the availability of such data.  The episode is hosted by Dr. Ulrik Stervbo and Dr. Zhaoqing Ding. Comments are welcome to the inbox of [email protected] or on social media under the tag #onAIRR. Further information can be found here: https://www.antibodysociety.org/the-airr-community/airr-c-podcast.

Dr. Xenophon Papademetris is Professor of Radiology and Biomedical Imaging, and Biomedical Engineering at Yale University, USA. The research of Prof. Papademetris is in the area of medical image analysis with a focus in the development of medical software. Dr. Papademetris provides an overview of the typical regulatory process for software classified as a medical device. We draw from his experience in the medical image field to design a high level route map for an imaginary company bringing to the market software to diagnose minimal residual disease. You can learn more about Medical Software development in Dr. Papademetris’s book Introduction to Medical Software: Foundations for Digital Health, Devices and Diagnostics (Cambridge University Press, 2022) and the Yale/Coursera class Introduction to Medical Software. The episode is hosted by Dr. Ulrik Stervbo and Dr. Zhaoqing Ding. Comments are welcome to the inbox of [email protected] or on social media under the tag #onAIRR. Further information can be found here: https://www.antibodysociety.org/the-airr-community/airr-c-podcast

Prof. Dr. Ralf Küppers is the director of Institute of Cell Biology (Tumor Research), University of Duisburg-Essen, Germany. The work of Prof. Küppers revolves around B cell differentiation and function together with pathogenesis of human B cell lymphomas - both Hodgkin and Non-Hodgkin lymphoma. We discuss how micro-dissection and Sanger sequencing is still the method of choice when analysing Hodgkin lymphoma and the V-gene usage and mutations in CLL as prognostic indicators before talking about tracking pathogenic clones when surveying for relapse during clinical follow up.  The episode is hosted by Dr. Ulrik Stervbo and Dr. Zhaoqing Ding. Comments are welcome to the inbox of [email protected] or on social media under the tag #onAIRR. Further information can be found here: https://www.antibodysociety.org/the-airr-community/airr-c-podcast. 

Vadim Nazarov is Co-Founder & CEO of the startup ImmunoMind. The company focuses on improving the design of adoptive T-cell therapies using multi-omics technologies. Vadim's career began at Dr. Dmitry Chudakov’s Laboratory of Adaptive Immunity, where he developed the now discontinued R-package TcR. The replacement package ‘immunarch’ is continuously developed by ImmunoMind.   The episode is hosted by Dr. Ulrik Stervbo and Dr. Zhaoqing Ding. Comments are welcome to the inbox of [email protected] or on social media under the hashtag #onAIRR. Further information can be found here: https://www.antibodysociety.org/the-airr-community/airr-c-podcast

Dr. Adi Barzel is an associate professor in the department of Biochemistry & Molecular Biology at Tel Aviv University, Tel Aviv, Israel. Adi is President at Israeli Society of Gene and Cell Therapy. Following Adi’s long standing interest in gene editing, we discuss the therapeutic potential based on Adi’s recent paper “In vivo engineered B cells secrete high titers of broadly neutralizing anti-HIV antibodies in mice” (Nat Biotechnol.; 2022; https://doi.org/10.1038/s41587-022-01328-9). We also briefly touch on a second paper on some of the problems with CRISPR-Cas9 gene editing (“Frequent aneuploidy in primary human T cells after CRISPR-Cas9 cleavage”;  Nat Biotechnol.; 2022; https://doi.org/10.1038/s41587-022-01377-0) iReceptor Plus Seminar Series - Nur-Taz Rahman from 10x Genomics and Kazuyoshi Ishigaki, Laboratory for Human Immunogenetics, RIKEN Center for Integrative Medical Sciences, Japan will present on October 27th (https://www.ireceptor-plus.com/news-and-events/seminars/) The episode is hosted by Dr. Ulrik Stervbo and Dr. Zhaoqing Ding.Comments are welcome to the inbox of [email protected] or on social media under the hashtag #onAIRR. Further information can be found here: https://www.antibodysociety.org/the-airr-community/airr-c-podcast

Dr. Encarnita Mariotti-Ferrandiz is associate professor in Immunology at Sorbonne Université, Paris, France. Encarnita is Chair-Elect of the AIRR-Community. The discussion focuses on sample quality and how to assess this. We draw on two papers during the discussion: “Benchmarking of T cell receptor repertoire profiling methods reveals large systematic biases” (Nature Biotechnology; 2021; https://doi.org/10.1038/s41587-020-0656-3) and “Biological controls for standardisation and interpretation of adaptive immune receptor repertoire profiling” (eLife; 2021;  https://doi.org/10.7554/eLife.66274). iReceptor Plus Seminar Series - Xiaole Shirley Liu from Dana-Farber Cancer Institute and Jeff Ruffolo from Johns Hopkins University will present on September 22, 2022: https://www.ireceptor-plus.com/news-and-events/seminars  The episode is hosted by Dr. Ulrik Stervbo and Dr. Zhaoqing Ding. Comments are welcome to the inbox of [email protected] or on social media under the hashtag #onAIRR. Further information can be found here: https://www.antibodysociety.org/the-airr-community/airr-c-podcast

Dr. Brian Corrie is a computer scientist from Simon Fraser University in British Columbia, Canada. Brian is the Technical Director for the iReceptor Plus Project, and architect behind the iReceptor repository (https://www.ireceptor-plus.com). Dr. Scott Christley‬ is a computational biologist from UT Southwestern, Texas, USA. Scott is the software development manager for VDJServer (https://vdjserver.org). In this episode we discuss possibilities for sharing AIRR-Seq data - repositories and metadata standards describing the samples and experimental process. We discuss AIRR Standards (https://docs.airr-community.org/en/stable) which includes MiAIRR Standard for dataset metadata and AIRR Data Commons, which is an API to query and download data from AIRR-Seq repositories. Complete and proper data annotation will bring fame and glory. iReceptor Plus Seminar Series - Ning Jiang from University of Pennsylvania, USA presents on July 28th: https://www.ireceptor-plus.com/news-and-events/seminars The episode is hosted by Dr. Ulrik Stervbo and Dr. Zhaoqing Ding. Comments are welcome to the inbox of [email protected] or on social media under the hashtag #onAIRR. Further information can be found here: https://www.antibodysociety.org/the-airr-community/airr-c-podcast