IRProfiler – a software toolbox for high throughput immune receptor profiling

Christos Maramis, Athanasios Gkoufas, Anna Vardi, Evangelia Stalika, Kostas Stamatopoulos, Anastasia Hatzidimitriou, Nicos Maglaveras, Ioanna Chouvarda

The study of the huge diversity of immune receptors, often referred to as immune repertoire profiling, is a prerequisite for diagnosis, prognostication and monitoring of hematological disorders. In the era of high-throughput sequencing (HTS), the abundance of immunogenetic data has revealed unprecedented opportunities for the thorough profiling of T-cell receptors (TR) and B-cell receptors (BcR). However, the volume of the data to be analyzed mandates for efficient and ease-to-use immune repertoire profiling software applications. This work introduces Immune Repertoire Profiler (IRProfiler), a novel software pipeline that delivers a number of core receptor repertoire quantification and comparison functionalities on high-throughput TR and BcR sequencing data. Adopting 5 alternative clonotype definitions, IRProfiler implements a series of algorithms for 1) data filtering, 2) calculation of clonotype diversity and expression, 3) calculation of gene usage for the V and J subgroups, 4) detection of shared and exclusive clonotypes among multiple repertoires, and 5) comparison of gene usage for V and J subgroups among multiple repertoires. IRProfiler has been implemented as a toolbox of the Galaxy bioinformatics platform, comprising 6 tools. Theoretical and experimental evaluation has shown that the tools of IRProfiler are able to scale well with respect to the size of input dataset(s). IRProfiler has been utilized by a number of recently published studies concerning hematological disorders. IRProfiler is made freely available via 3 distribution channels, including the Galaxy Tool Shed. Despite being a new entry in a crowded ecosystem of immune repertoire profiling software, IRProfiler founds its added value on its support for alternative clonotype definitions in conjunction with a combination of properties stemming from its user-centric design, namely ease-of-use, ease-of-access, exploitability of the output data, and analysis flexibility.