Abstract
The antibody repertoire is a critical component of the adaptive immune system and is believed to reflect an individual’s immune history and current immune status. Delineating the antibody repertoire has advanced our understanding of humoral immunity, facilitated antibody discovery, and showed great potential for improving the diagnosis and treatment of disease. However, no tool to date has effectively integrated big Rep-seq data and prior knowledge of functional antibodies to elucidate the remarkably diverse antibody repertoire. We developed a Rep-seq dataset Analysis Platform with an Integrated antibody Database (RAPID; https://rapid.zzhlab.org/), a free and web-based tool that allows researchers to process and analyse Rep-seq datasets. RAPID consolidates 521 WHO-recognized therapeutic antibodies, 88,059 antigen- or disease-specific antibodies, and 306 million clones extracted from 2,449 human IGH Rep-seq datasets generated from individuals with 29 different health conditions. RAPID also integrates a standardized Rep-seq dataset analysis pipeline to enable users to upload and analyse their datasets. In the process, users can also select set of existing repertoires for comparison. RAPID automatically annotates clones based on integrated therapeutic and known antibodies, and users can easily query antibodies or repertoires based on sequence or optional keywords. With its powerful analysis functions and rich set of antibody and antibody repertoire information, RAPID will benefit researchers in adaptive immune studies.
Highlights
Antibodies (Abs), specialized immunoglobulins secreted by B cells, play a pivotal role in antigen recognition and neutralization
The RAPID platform builds from the availability of large Rep-seq datasets and a variety of functional antibody sequences to provide three main functionalities, including a Rep-seq dataset analysis platform, antibody annotation, and antibody and repertoire query (Figure 2)
To allow users to analyse their Rep-seq datasets rapidly, we developed a web-based automatic human IGH Rep-seq dataset analysis platform that can perform both low-level (Figure 2A) and high-level (Figure 2B) analyses
Summary
Antibodies (Abs), specialized immunoglobulins secreted by B cells, play a pivotal role in antigen recognition and neutralization. There are several Rep-seq dataset analysis platforms, including ARGalaxy, which can process raw reads and extract repertoire features online [29], BRepertoire, which concentrates on statistical analysis [30], SONAR, which is focused on inferring antibody ontogenies [31], and IgBLAST and IMGT/HighVQUEST, which allow V(D)J gene annotation [32, 33]. While all these previous tools are helpful, there was no platform that integrates all known antibodies, a large number of repertoires, and a feature-rich comprehensive analysis pipeline. As a user-friendly Rep-seq dataset analysis platform, RAPID will assist researchers in identifying distinct repertoire signatures and antigen-specific clones in the context of various health conditions on a large scale and accelerate the applications of Rep-seq
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