NGS immunogenetics has applications in both diagnostics (e.g., assessment of clonality in samples investigated for a possible lymphoproliferation or detection of minimal residual disease in patients with lymphoid malignancies) and research. ) gene repertoires using next-generation sequencing (NGS) technologies advanced our understanding of various clinical conditionsĪnd biological processes, extending from infections, vaccination, autoimmunity, to malignancy. Profiling the B-cell receptor immunoglobulin (BcR IG) and T-cell receptor (TR Relevant to mention, TRIP enables a high level of customization through the integration of various options in key aspects of the analysis, such as clonotype definition and computation, hence allowing for flexibility without compromising on accuracy. Subsequently, it provides in-depth analysis of antigen receptor gene rearrangements, including (a) clonality assessment (b) extraction of variable (V), diversity (D), and joining (J) gene repertoires (c) CDR3 characterization at both the nucleotide and amino acid level and (d) somatic hypermutation analysis, in the case of immunoglobulin gene rearrangements.
Tcr repertoire imgt series#
TRIP has the potential to perform robust immunoprofiling analysis through the extraction and processing of the IMGT/HighV-Quest output, via a series of functions, ensuring the analysis of high-quality, biologically relevant data through a multilevel process of data filtering. Several bioinformatics workflows have been developed to this end, including the T-cell receptor/immunoglobulin profiler (TRIP), a web application implemented in R shiny, specifically designed for the purposes of comprehensive repertoire analysis, which is the focus of this chapter. The study of antigen receptor gene repertoires using next-generation sequencing (NGS) technologies has disclosed an unprecedented depth of complexity, requiring novel computational and analytical solutions. IMGT/V-QUEST and IMGT/HighV-QUEST are available at the IMGT(®) Home page. IMGT/HighV-QUEST, the high-throughput version of IMGT/V-QUEST, implemented to answer the needs of deep sequencing data analysis from Next Generation Sequencing (NGS), allows the analysis of thousands of IG and TR sequences in a single run. IMGT/V-QUEST integrates IMGT/JunctionAnalysis for a detailed analysis of the V-J and V-D-J junctions and IMGT/Automat for a complete annotation of the sequences and also provides IMGT Collier de Perles. The tool describes the V-REGION mutations and identifies the hot spot positions in the closest germline V gene. IMGT/V-QUEST identifies the V, D, J genes and alleles by alignment with the germline IG and TR gene and allele sequences of the IMGT reference directory. These mechanisms include the combinatorial rearrangements of the variable (V), diversity (D) and joining (J) genes, the N-diversity (deletion and addition at random of nucleotides during the V-(D)-J rearrangement) and, for IG, somatic hypermutations. This huge diversity results from mechanisms that occur at the DNA level during the IG and TR molecular synthesis. The expressed IG and TR repertoires represent a potential of 10(12) IG and 10(12) TR per individual. The analysis of these antigen receptors represents a crucial challenge for the study of the adaptive immune response in normal and disease-related situations. IMGT/V-QUEST is the highly customized and integrated online IMGT(®) tool for the standardized analysis of the immunoglobulin (IG) or antibody and T cell receptor (TR) rearranged nucleotide sequences.
0 kommentar(er)
