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IMGT/HighV-QUEST Statistical Significance of IMGT Clonotype (AA) Diversity per Gene for Standardized Comparisons of Next Generation Sequencing Immunoprofiles of Immunoglobulins and T Cell Receptors.

Aouinti S, Malouche D, Giudicelli V, Kossida S, Lefranc MP - PLoS ONE (2015)

Bottom Line: The adaptive immune responses of humans and of other jawed vertebrate species (gnasthostomata) are characterized by the B and T cells and their specific antigen receptors, the immunoglobulins (IG) or antibodies and the T cell receptors (TR) (up to 2.1012 different IG and TR per individual).It provides the identification of the variable (V), diversity (D) and joining (J) genes and alleles, analysis of the V-(D)-J junction and complementarity determining region 3 (CDR3) and the characterization of the 'IMGT clonotype (AA)' (AA for amino acid) diversity and expression.The procedure is generic and suitable for evaluating significance of the IMGT clonotype (AA) diversity and expression per gene, and for any IG and TR immunoprofiles of any species.

View Article: PubMed Central - PubMed

Affiliation: IMGT, the international ImMunoGeneTics information system, Laboratoire d'ImmunoGénétique Moléculaire LIGM, Institut de Génétique Humaine IGH, UPR CNRS 1142, Montpellier University, Montpellier cedex 5, France.

ABSTRACT
The adaptive immune responses of humans and of other jawed vertebrate species (gnasthostomata) are characterized by the B and T cells and their specific antigen receptors, the immunoglobulins (IG) or antibodies and the T cell receptors (TR) (up to 2.1012 different IG and TR per individual). IMGT, the international ImMunoGeneTics information system (http://www.imgt.org), was created in 1989 by Marie-Paule Lefranc (Montpellier University and CNRS) to manage the huge and complex diversity of these antigen receptors. IMGT built on IMGT-ONTOLOGY concepts of identification (keywords), description (labels), classification (gene and allele nomenclature) and numerotation (IMGT unique numbering), is at the origin of immunoinformatics, a science at the interface between immunogenetics and bioinformatics. IMGT/HighV-QUEST, the first web portal, and so far the only one, for the next generation sequencing (NGS) analysis of IG and TR, is the paradigm for immune repertoire standardized outputs and immunoprofiles of the adaptive immune responses. It provides the identification of the variable (V), diversity (D) and joining (J) genes and alleles, analysis of the V-(D)-J junction and complementarity determining region 3 (CDR3) and the characterization of the 'IMGT clonotype (AA)' (AA for amino acid) diversity and expression. IMGT/HighV-QUEST compares outputs of different batches, up to one million nucleotide sequencesfor the statistical module. These high throughput IG and TR repertoire immunoprofiles are of prime importance in vaccination, cancer, infectious diseases, autoimmunity and lymphoproliferative disorders, however their comparative statistical analysis still remains a challenge. We present a standardized statistical procedure to analyze IMGT/HighV-QUEST outputs for the evaluation of the significance of the IMGT clonotype (AA) diversity differences in proportions, per gene of a given group, between NGS IG and TR repertoire immunoprofiles. The procedure is generic and suitable for evaluating significance of the IMGT clonotype (AA) diversity and expression per gene, and for any IG and TR immunoprofiles of any species.

No MeSH data available.


Related in: MedlinePlus

Multiple testing procedures visualization plots.Multiple testing procedures visualization plots are displayed for comparison of the differences in proportions for IMGT clonotypes (AA) with a gene of a given group (TRBV, TRBD or TRBJ), between two T cell populations (CD4- and CD4+) at four time points (Pre, d3, d8 and d26). The following procedures: Bonferroni, Holm, Hochberg, ŠidákSS and ŠidákSD, BH and BY were applied. Left panel (A, C, E, G): Line graphs showing the number of rejected  hypotheses against the Type I error rate. Dotted lines represent unadjusted p-values (rawp) whereas colored lines represent ajusted p-values of the seven procedures. A vertical line corresponds to a Type I error rate (α-level) at 0.05 (significance level of 5%). Right panel (B, D, F, H): Negative decimal logarithms (-log10) of unadjusted p-values (black symbols) and adjusted p-values (colored symbols) against the test statistic z-scores. Two areas in scatter plots (top left and top right) correspond to significant differences in proportions and they are delimited at a significance level of 5% (0.05) by -log10(p-values) > 1.3 (horizontal line) and by z-scores (< -1.96 for negative differences or > 1.96 for positive differences) (vertical line).
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pone.0142353.g002: Multiple testing procedures visualization plots.Multiple testing procedures visualization plots are displayed for comparison of the differences in proportions for IMGT clonotypes (AA) with a gene of a given group (TRBV, TRBD or TRBJ), between two T cell populations (CD4- and CD4+) at four time points (Pre, d3, d8 and d26). The following procedures: Bonferroni, Holm, Hochberg, ŠidákSS and ŠidákSD, BH and BY were applied. Left panel (A, C, E, G): Line graphs showing the number of rejected hypotheses against the Type I error rate. Dotted lines represent unadjusted p-values (rawp) whereas colored lines represent ajusted p-values of the seven procedures. A vertical line corresponds to a Type I error rate (α-level) at 0.05 (significance level of 5%). Right panel (B, D, F, H): Negative decimal logarithms (-log10) of unadjusted p-values (black symbols) and adjusted p-values (colored symbols) against the test statistic z-scores. Two areas in scatter plots (top left and top right) correspond to significant differences in proportions and they are delimited at a significance level of 5% (0.05) by -log10(p-values) > 1.3 (horizontal line) and by z-scores (< -1.96 for negative differences or > 1.96 for positive differences) (vertical line).

Mentions: In order to visualize the statistical analysis results obtained using the multiple testing procedures, two types of plots (line graphs and scatter plots, Fig 2) were generated for each comparison using the Bioconductor (http://www.bioconductor.org) R package multtest [38].


IMGT/HighV-QUEST Statistical Significance of IMGT Clonotype (AA) Diversity per Gene for Standardized Comparisons of Next Generation Sequencing Immunoprofiles of Immunoglobulins and T Cell Receptors.

Aouinti S, Malouche D, Giudicelli V, Kossida S, Lefranc MP - PLoS ONE (2015)

Multiple testing procedures visualization plots.Multiple testing procedures visualization plots are displayed for comparison of the differences in proportions for IMGT clonotypes (AA) with a gene of a given group (TRBV, TRBD or TRBJ), between two T cell populations (CD4- and CD4+) at four time points (Pre, d3, d8 and d26). The following procedures: Bonferroni, Holm, Hochberg, ŠidákSS and ŠidákSD, BH and BY were applied. Left panel (A, C, E, G): Line graphs showing the number of rejected  hypotheses against the Type I error rate. Dotted lines represent unadjusted p-values (rawp) whereas colored lines represent ajusted p-values of the seven procedures. A vertical line corresponds to a Type I error rate (α-level) at 0.05 (significance level of 5%). Right panel (B, D, F, H): Negative decimal logarithms (-log10) of unadjusted p-values (black symbols) and adjusted p-values (colored symbols) against the test statistic z-scores. Two areas in scatter plots (top left and top right) correspond to significant differences in proportions and they are delimited at a significance level of 5% (0.05) by -log10(p-values) > 1.3 (horizontal line) and by z-scores (< -1.96 for negative differences or > 1.96 for positive differences) (vertical line).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4634997&req=5

pone.0142353.g002: Multiple testing procedures visualization plots.Multiple testing procedures visualization plots are displayed for comparison of the differences in proportions for IMGT clonotypes (AA) with a gene of a given group (TRBV, TRBD or TRBJ), between two T cell populations (CD4- and CD4+) at four time points (Pre, d3, d8 and d26). The following procedures: Bonferroni, Holm, Hochberg, ŠidákSS and ŠidákSD, BH and BY were applied. Left panel (A, C, E, G): Line graphs showing the number of rejected hypotheses against the Type I error rate. Dotted lines represent unadjusted p-values (rawp) whereas colored lines represent ajusted p-values of the seven procedures. A vertical line corresponds to a Type I error rate (α-level) at 0.05 (significance level of 5%). Right panel (B, D, F, H): Negative decimal logarithms (-log10) of unadjusted p-values (black symbols) and adjusted p-values (colored symbols) against the test statistic z-scores. Two areas in scatter plots (top left and top right) correspond to significant differences in proportions and they are delimited at a significance level of 5% (0.05) by -log10(p-values) > 1.3 (horizontal line) and by z-scores (< -1.96 for negative differences or > 1.96 for positive differences) (vertical line).
Mentions: In order to visualize the statistical analysis results obtained using the multiple testing procedures, two types of plots (line graphs and scatter plots, Fig 2) were generated for each comparison using the Bioconductor (http://www.bioconductor.org) R package multtest [38].

Bottom Line: The adaptive immune responses of humans and of other jawed vertebrate species (gnasthostomata) are characterized by the B and T cells and their specific antigen receptors, the immunoglobulins (IG) or antibodies and the T cell receptors (TR) (up to 2.1012 different IG and TR per individual).It provides the identification of the variable (V), diversity (D) and joining (J) genes and alleles, analysis of the V-(D)-J junction and complementarity determining region 3 (CDR3) and the characterization of the 'IMGT clonotype (AA)' (AA for amino acid) diversity and expression.The procedure is generic and suitable for evaluating significance of the IMGT clonotype (AA) diversity and expression per gene, and for any IG and TR immunoprofiles of any species.

View Article: PubMed Central - PubMed

Affiliation: IMGT, the international ImMunoGeneTics information system, Laboratoire d'ImmunoGénétique Moléculaire LIGM, Institut de Génétique Humaine IGH, UPR CNRS 1142, Montpellier University, Montpellier cedex 5, France.

ABSTRACT
The adaptive immune responses of humans and of other jawed vertebrate species (gnasthostomata) are characterized by the B and T cells and their specific antigen receptors, the immunoglobulins (IG) or antibodies and the T cell receptors (TR) (up to 2.1012 different IG and TR per individual). IMGT, the international ImMunoGeneTics information system (http://www.imgt.org), was created in 1989 by Marie-Paule Lefranc (Montpellier University and CNRS) to manage the huge and complex diversity of these antigen receptors. IMGT built on IMGT-ONTOLOGY concepts of identification (keywords), description (labels), classification (gene and allele nomenclature) and numerotation (IMGT unique numbering), is at the origin of immunoinformatics, a science at the interface between immunogenetics and bioinformatics. IMGT/HighV-QUEST, the first web portal, and so far the only one, for the next generation sequencing (NGS) analysis of IG and TR, is the paradigm for immune repertoire standardized outputs and immunoprofiles of the adaptive immune responses. It provides the identification of the variable (V), diversity (D) and joining (J) genes and alleles, analysis of the V-(D)-J junction and complementarity determining region 3 (CDR3) and the characterization of the 'IMGT clonotype (AA)' (AA for amino acid) diversity and expression. IMGT/HighV-QUEST compares outputs of different batches, up to one million nucleotide sequencesfor the statistical module. These high throughput IG and TR repertoire immunoprofiles are of prime importance in vaccination, cancer, infectious diseases, autoimmunity and lymphoproliferative disorders, however their comparative statistical analysis still remains a challenge. We present a standardized statistical procedure to analyze IMGT/HighV-QUEST outputs for the evaluation of the significance of the IMGT clonotype (AA) diversity differences in proportions, per gene of a given group, between NGS IG and TR repertoire immunoprofiles. The procedure is generic and suitable for evaluating significance of the IMGT clonotype (AA) diversity and expression per gene, and for any IG and TR immunoprofiles of any species.

No MeSH data available.


Related in: MedlinePlus