ImmunExplorer (IMEX): a software framework for diversity and clonality analyses of immunoglobulins and T cell receptors on the basis of IMGT/HighV-QUEST preprocessed NGS data.

Susanne Schaller,Johannes Weinberger,Christian Gabriel,Stephan M Winkler,Raul Jimenez-Heredia,Rainer Oberbauer,Martin Danzer

doi:10.1186/s12859-015-0687-9

Abstract

BackgroundToday’s modern research of B and T cell antigen receptors (the immunoglobulins (IG) or antibodies and T cell receptors (TR)) forms the basis for detailed analyses of the human adaptive immune system. For instance, insights in the state of the adaptive immune system provide information that is essentially important in monitoring transplantation processes and the regulation of immune suppressiva. In this context, algorithms and tools are necessary for analyzing the IG and TR diversity on nucleotide as well as on amino acid sequence level, identifying highly proliferated clonotypes, determining the diversity of the cell repertoire found in a sample, comparing different states of the human immune system, and visualizing all relevant information.ResultsWe here present IMEX, a software framework for the detailed characterization and visualization of the state of human IG and TR repertoires. IMEX offers a broad range of algorithms for statistical analysis of IG and TR data, CDR and V-(D)-J analysis, diversity analysis by calculating the distribution of IG and TR, calculating primer efficiency, and comparing multiple data sets. We use a mathematical model that is able to describe the number of unique clonotypes in a sample taking into account the true number of unique sequences and read errors; we heuristically optimize the parameters of this model. IMEX uses IMGT/HighV-QUEST analysis outputs and includes methods for splitting and merging to enable the submission to this portal and to combine the outputs results, respectively. All calculation results can be visualized and exported.ConclusionIMEX is an user-friendly and flexible framework for performing clonality experiments based on CDR and V-(D)-J rearranged regions, diversity analysis, primer efficiency, and various different visualization experiments. Using IMEX, various immunological reactions and alterations can be investigated in detail. IMEX is freely available for Windows and Unix platforms at http://bioinformatics.fh-hagenberg.at/immunexplorer/.Electronic supplementary materialThe online version of this article (doi:10.1186/s12859-015-0687-9) contains supplementary material, which is available to authorized users.

Highlights

Today’s modern research of B and T cell antigen receptors (the immunoglobulins (IG) or antibodies and T cell receptors (TR)) forms the basis for detailed analyses of the human adaptive immune system
ImmunoSEQ mainly places emphasis on statistical analysis and visualization of IG and TR data. Whereas most of these tools/frameworks are focused on one cell type or on one specific type of analysis, our here presented framework IMEX has been designed for comprehensive, in-depth analysis of human antigen IG and TR repertoires based on next-generation sequencing (NGS) data
Preprocessing methods for the IMGT/HighV-QUEST submission The IMGT/HighV-QUEST online portal enables uploading and processing of up to 500,000 sequences, preprocessing methods have been developed in IMEX: FASTA files can be split into several files to prepare the upload to the IMGT information system; after uploading to IMGT/HighV-QUEST [16] at IMGT, the international ImMunoGeneTics information system [17] and analyzing, the compressed output files can be merged to one compressed data file

Summary

Introduction

Today’s modern research of B and T cell antigen receptors (the immunoglobulins (IG) or antibodies and T cell receptors (TR)) forms the basis for detailed analyses of the human adaptive immune system. Insights in the state of the adaptive immune system provide information that is essentially important in monitoring transplantation processes and the regulation of immune suppressiva In this context, algorithms and tools are necessary for analyzing the IG and TR diversity on nucleotide as well as on amino acid sequence level, identifying highly proliferated clonotypes, determining the diversity of the cell repertoire found in a sample, comparing different states of the human immune system, and visualizing all relevant information. Immune repertoire is a term that is commonly used in immunology to describe the level of diversity and clonality of B and T cell antigen receptors, the immunoglobulins (IG) or antibodies and T cell receptors (TR). An important principle called allelic exclusion ensures that only one receptor specificity is expressed per B or T cell

Methods

Results

Conclusion