On AIRR - Immune receptors in the clinic (AIRR-Community)

Anton Langerak is Professor and head of Laboratory Medical Immunology at the Department of Immunology, Erasmus MC in Rotterdam, Netherlands and chair of coordination of the EuroClonality-NGS working group (https://euroclonality.org/ngs/about and https://euroclonality.org). He has been working on chronic lymphocytic leukemia (CLL) for many years and in this episode we discuss the signatures of B cell receptors in CLL.

AIRR Community Meeting VI: “Exploring New Frontiers”: https://www.antibodysociety.org/the-airr-community/meetings/airr-community-meeting-vi-exploring-new-frontiers

Comments are welcome at the inbox of onairr@airr-community.org or on social media under the hashtag #onAIRR. Further information can be found here: https://www.antibodysociety.org/the-airr-community/airr-c-podcast

Today we discuss machine learning with Dr. Lindsay Cowell and Dr. Victor Greiff. Machine learning is about pattern recognition and in AIRR-seq the patterns link to diseases and antigen binding. AIRR is nearly a perfect machine learning problem because the underlying patterns are unclear and complex - it is essentially looking for the needle in a needle stack.

Dr. Cowell is from the Biomedical Informatics Division in the Department of Clinical Sciences, UT Southwestern, USA and Dr. Greiff heads  the Laboratory for Computational and Systems Immunology at the Department of Immunology of University of Oslo, Norway.

The episode is hosted by Dr. Ulrik Stervbo and Dr. Zhaoqing Ding.

Comments are welcome to the inbox of onairr@airr-community.org  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. 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 onairr@airr-community.org or on social media under the tag #onAIRR. Further information can be found here: https://www.antibodysociety.org/the-airr-community/airr-c-podcast.

In this episode of On AIRR, Dr. Bjoern Peters, Professor at the La Jolla Institute for Immunology (LJI), explores how high-quality data serves as the foundation for advancing AI-based immunological predictions and diagnostics.

Originally from Germany, Dr. Peters began his academic journey in theoretical physics at Hamburg, focusing on quantum optics, before pivoting to biophysics during his PhD at Humboldt University. This shift was inspired by the challenge of understanding epitope presentation pathways and the limitations of epitope-prediction algorithms, which led him to work with Dr. Alessandro Sette at LJI to develop the Immune Epitope Database (IEDB) — the world’s largest resource for immune epitope data.

Throughout the conversation, Dr. Peters traces the evolution of epitope research, starting with his work on MHC-peptide binding predictions and expanding into broader immunological data collection. He emphasizes that high-quality datasets often outcompete algorithmic improvements and shares the story of how the IEDB was established to consolidate immune epitope data. The conversation explores the status of data standardization and use of ontologies in structuring biomedical data, particularly in immunology. Dr. Peters highlights how work done by the IEDB and the Adaptive Immune Receptor Repertoire Community (AIRR-C) in these areas is critical for advancing immunology and enabling prediction and diagnostics. Finally, the discussion covers challenges of predicting epitopes from immune repertoires, the growing interest in using AIRR sequencing for diagnostics, and the importance of rigorous, unbiased validation of prediction models for clinical applications. 

Comments are welcome to the inbox of onairr@airr-community.org or on social media under the tag #onAIRR. Further information can be found here: https://www.antibodysociety.org/the-airr-community/airr-c-podcast.

The episode is hosted by Dr. Ulrik Stervbo and Dr. Zhaoqing Ding.

 Announcements and links

• Peters Lab https://www.lji.org/labs/peters-lab
• Tools mentioned:
  • Immune Epitope Database (IEDB) https://www.iedb.org 
  • Ontology for Biomedical Investigations (OBI) https://obi-ontology.org 
• Other:
  • Adaptive Immune Receptor Repertoire Community (AIRR-C) https://www.airr-community.org
  • The Antibody Society (TAbS) https://www.antibodysociety.org
  • Antibody News Podcast, by TAbS https://www.antibodysociety.org/antibody-news-podcast
  • Sette Lab https://www.lji.org/labs/sette-lab 

In this episode, we discuss the interest of Lindsay Cowell from UT Southwestern in creating a framework to enable deeper understanding of AIRR-Seq in health and disease.

Comments are welcome at the inbox of onairr@airr-community.org or on social media under the hashtag #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 onairr@airr-community.org 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 onairr@airr-community.org 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 onairr@airr-community.org 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. Jacob Glanville is founder and CEO of Centivax and  founder of Distributed Bio, acquired by Charles River in 2021. His work focuses on understanding and engineering  the repertoires of T and B cells to improve the response to pathogens. In this episode we discuss how to analyze receptor specificity and use this to create therapeutic antibodies and optimize vaccine response.

AIRR Community Meeting VI: “Exploring New Frontiers”: https://www.antibodysociety.org/the-airr-community/meetings/airr-community-meeting-vi-exploring-new-frontiers

iReceptor+ Seminar Series: http://www.ireceptor-plus.com/news-and-events/seminars

Comments are welcome to the inbox of onairr@airr-community.org 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 onairr@airr-community.org or on social media under the hashtag #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 onairr@airr-community.org  or on social media under the tag #onAIRR. Further information can be found here: https://www.antibodysociety.org/the-airr-community/airr-c-podcast.

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 onairr@airr-community.org  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 onairr@airr-community.org or on social media under the tag #onAIRR. Further information can be found here: https://www.antibodysociety.org/the-airr-community/airr-c-podcast

Today's guest is Nina Luning Prak from the University of Pennsylvania. We talk a bit about the AIRR-Community but mostly about diagnosis of B or T cell malignancies and minimal residual disease evaluation and tracking of B cell clones in autoimmunity.

Comments are welcome at the inbox of onairr@airr-community.org 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. Thierry Mora and Dr. Aleksandra Walczak co-lead the Statistical biophysics group within Laboratoire de physique de l'ENS (LPENS) at the Ecole normale supérieure (Paris, France). Physicists by training, Dr. Mora and Dr. Walczak entered the field of the analysis of the immune system in a time when the first AIRR-seq datasets were becoming available. They have applied biophysics, neuroscience, and information theory perspectives to understand V(D)J recombination and quantify diversity. The group has published many software tools for the analysis of immune repertoires, including IGoR (to infer V(D)J recombination related processes from sequencing data), Sonia (infer selection pressures on features of amino acid CDR3 sequences), ALICE (detect TCR involved in immune responses from single RepSeq datasets), and PUBLIC (for analyzing sharing of TCRs, and predict public clones).

In this episode of On AIRR, Dr. Mora and Dr. Walczak discuss the relevance and challenges of quantifying diversity and the questions that remain unanswered. They think of immune repertoire diversity in the same way as one could think of English language sentences, and try to learn the grammar of the combinations and quantify it. They also provide an overview of some of the software tools developed by their group.

Comments are welcome to the inbox of onairr@airr-community.org  or on social media under the tag #onAIRR. Further information can be found here: https://www.antibodysociety.org/the-airr-community/airr-c-podcast.   The episode is hosted by Dr. Ulrik Stervbo and Dr. Zhaoqing Ding.

Announcements and links

• Statistical biophysics @ ENS. The website of the group. https://sites.google.com/view/statbiophysens/home
• Tools mentioned:
  • IGoR: https://github.com/statbiophys/IGoR
  • Sonia: https://github.com/statbiophys/SONIA
  • SoNNia: https://github.com/statbiophys/sonnia
  • ALICE: https://github.com/pogorely/ALICE
  • PUBLIC: https://github.com/yuvalel/PUBLIC

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 onairr@airr-community.org 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. 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 onairr@airr-community.org  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