The development of novel effective medical treatments is one of the most important and expected beneficial effects of the AI revolution. This decade is witnessing the rise of AI models able to predict complex properties for protein-protein interactions that hold great promise in assisting in the development of antibody therapeutics and vaccines, including for diseases that long eluded us in the pursuit of an effective treatment. This paper introduces this area of research in a language accessible to an AI researcher, exploring the biological problems that can be solved by AI models, as well as the general context to make solutions feasible in practical scenarios. We survey the main current trends and works in this research area and point towards current still unsolved challenges and trade offs. We expect this paper will be extremely helpful for AI researchers trying to join the field, as well as for researchers already working in one of the subtopics that wish to have a better understanding of the general context around it.

SUMMARY: Antibody repertoires reveal insights into the biology of the adaptive immune system and empower diagnostics and therapeutics. There are currently multiple tools available for the annotation of antibody sequences. All downstream analyses such as choosing lead drug candidates depend on the correct annotation of these sequences; however, a thorough comparison of the performance of these tools has not been investigated. Here, we benchmark the performance of commonly used immunoinformatic tools, i.e. IMGT/HighV-QUEST, IgBLAST and MiXCR, in terms of reproducibility of annotation output, accuracy and speed using simulated and experimental high-throughput sequencing datasets.We analyzed changes in IMGT reference germline database in the last 10 years in order to assess the reproducibility of the annotation output. We found that only 73/183 (40%) V, D and J human genes were shared between the reference germline sets used by the tools. We found that the annotation results differed between tools. In terms of alignment accuracy, MiXCR had the highest average frequency of gene mishits, 0.02 mishit frequency and IgBLAST the lowest, 0.004 mishit frequency. Reproducibility in the output of complementarity determining three regions (CDR3 amino acids) ranged from 4.3% to 77.6% with preprocessed data. In addition, run time of the tools was assessed: MiXCR was the fastest tool for number of sequences processed per unit of time. These results indicate that immunoinformatic analyses greatly depend on the choice of bioinformatics tool. Our results support informed decision-making to immunoinformaticians based on repertoire composition and sequencing platforms. AVAILABILITY AND IMPLEMENTATION: All tools utilized in the paper are free for academic use. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.