Immunoglobulins or antibodies are the main effector molecules of the B-cell lineage and are encoded by hundreds of variable (V), diversity (D), and joining (J) germline genes, which recombine to generate enormous IG diversity. Recently, high-throughput adaptive immune receptor repertoire sequencing (AIRR-seq) of recombined V-(D)-J genes has offered unprecedented insights into the dynamics of IG repertoires in health and disease. Faithful biological interpretation of AIRR-seq studies depends upon the annotation of raw AIRR-seq data, using reference germline gene databases to identify the germline genes within each rearrangement.
View Article and Find Full Text PDFIncreased interest in the immune system's involvement in pathophysiological phenomena coupled with decreased DNA sequencing costs have led to an explosion of antibody and T cell receptor sequencing data collectively termed "adaptive immune receptor repertoire sequencing" (AIRR-seq or Rep-Seq). The AIRR Community has been actively working to standardize protocols, metadata, formats, APIs, and other guidelines to promote open and reproducible studies of the immune repertoire. In this paper, we describe the work of the AIRR Community's Data Representation Working Group to develop standardized data representations for storing and sharing annotated antibody and T cell receptor data.
View Article and Find Full Text PDFNext-generation sequencing allows the characterization of the adaptive immune receptor repertoire (AIRR) in exquisite detail. These large-scale AIRR-seq data sets have rapidly become critical to vaccine development, understanding the immune response in autoimmune and infectious disease, and monitoring novel therapeutics against cancer. However, at present there is no easy way to compare these AIRR-seq data sets across studies and institutions.
View Article and Find Full Text PDFBackground: The genes that produce antibodies and the immune receptors expressed on lymphocytes are not germline encoded; rather, they are somatically generated in each developing lymphocyte by a process called V(D)J recombination, which assembles specific, independent gene segments into mature composite genes. The full set of composite genes in an individual at a single point in time is referred to as the immune repertoire. V(D)J recombination is the distinguishing feature of adaptive immunity and enables effective immune responses against an essentially infinite array of antigens.
View Article and Find Full Text PDFGenotyping experiments are widely used in clinical and basic research laboratories to identify associations between genetic variations and normal/abnormal phenotypes. Genotyping assay techniques vary from single genomic regions that are interrogated using PCR reactions to high throughput assays examining genome-wide sequence and structural variation. The resulting genotype data may include millions of markers of thousands of individuals, requiring various statistical, modeling or other data analysis methodologies to interpret the results.
View Article and Find Full Text PDFWe describe a novel approach to genetic association analyses with proteins sub-divided into biologically relevant smaller sequence features (SFs), and their variant types (VTs). SFVT analyses are particularly informative for study of highly polymorphic proteins such as the human leukocyte antigen (HLA), given the nature of its genetic variation: the high level of polymorphism, the pattern of amino acid variability, and that most HLA variation occurs at functionally important sites, as well as its known role in organ transplant rejection, autoimmune disease development and response to infection. Further, combinations of variable amino acid sites shared by several HLA alleles (shared epitopes) are most likely better descriptors of the actual causative genetic variants.
View Article and Find Full Text PDFThe immune response HLA class II DRB1 gene provides the major genetic contribution to Juvenile Idiopathic Arthritis (JIA), with a hierarchy of predisposing through intermediate to protective effects. With JIA, and the many other HLA associated diseases, it is difficult to identify the combinations of biologically relevant amino acid (AA) residues directly involved in disease due to the high level of HLA polymorphism, the pattern of AA variability, including varying degrees of linkage disequilibrium (LD), and the fact that most HLA variation occurs at functionally important sites. In a subset of JIA patients with the clinical phenotype oligoarticular-persistent (OP), we have applied a recently developed novel approach to genetic association analyses with genes/proteins sub-divided into biologically relevant smaller sequence features (SFs), and their "alleles" which are called variant types (VTs).
View Article and Find Full Text PDFThe Minimum Information for Biological and Biomedical Investigations (MIBBI) project provides a resource for those exploring the range of extant minimum information checklists and fosters coordinated development of such checklists.
View Article and Find Full Text PDFWe report here a strategy for the photolithographic synthesis of diverse, spatially addressable arrays of cyclic peptides which employs a differential deprotection strategy for the combinatorial addition of side chains to a pre-fabricated cyclic core.
View Article and Find Full Text PDFThere has been increasing interest and efforts devoted to developing biosensor technologies for identifying pathogens, particularly in the biothreat area. In this study, a universal set of short 12- and 13-mer oligonucleotide probes was derived independently of a priori genomic sequence information and used to generate unique species-dependent genomic hybridization signatures. The probe set sequences were algorithmically generated to be maximally distant in sequence space and not dependent on the sequence of any particular genome.
View Article and Find Full Text PDFWe describe a novel photolithographic approach to the synthesis of peptoids (oligo-N-substituted glycines). This strategy enables the construction of a spatially addressable peptoid microarray, thus providing a potentially powerful tool for the discovery of protein ligands.
View Article and Find Full Text PDF