ImmunoGlobulin galaxy (IGGalaxy) for simple determination and quantitation of immunoglobulin heavy chain rearrangements from NGS.

Background: Sequence analysis of immunoglobulin heavy chain (IGH) gene rearrangements and frequency analysis is a powerful tool for studying the immune repertoire, immune responses and immune dysregulation in health and disease. The challenge is to provide user friendly, secure and reproducible analytical services that are available for both small and large laboratories which are determining VDJ repertoire using NGS technology.

Results: In this study we describe ImmunoGlobulin Galaxy (IGGalaxy)- a convenient web based application for analyzing next-generation sequencing results and reporting IGH gene rearrangements for both repertoire and clonality studies.

Similar recombination-activating gene (RAG) mutations result in similar immunobiological effects but in different clinical phenotypes.

Background: V(D)J recombination takes place during lymphocyte development to generate a large repertoire of T- and B-cell receptors. Mutations in recombination-activating gene 1 (RAG1) and RAG2 result in loss or reduction of V(D)J recombination. It is known that different mutations in RAG genes vary in residual recombinase activity and give rise to a broad spectrum of clinical phenotypes.

Extensive variation in gene copy number at the killer immunoglobulin-like receptor locus in humans.

Killer immunoglobulin-like receptors (KIRs) are involved in the regulation of natural killer cell cytotoxicity. Within the human genome seventeen KIR genes are present, which all contain a large number of allelic variants. The high level of homology among KIR genes has hampered KIR genotyping in larger cohorts, and determination of gene copy number variation (CNV) has been difficult.

Recent advances in i-Gene tools and analysis: microarrays, next generation sequencing and mass spectrometry.

Recent advances in technology and associated methodology have made the current period one of the most exciting in molecular biology and medicine. Underlying these is an appreciation that modern research is driven by increasing large amounts of data being interpreted by interdisciplinary collaborative teams which are often geographically dispersed. The availability of cheap computing power, high speed informatics networks and high quality analysis software has been essential to this as has the application of modern quality assurance methodologies.

Absence of common somatic alterations in genes on 1p and 19q in oligodendrogliomas.

A common and histologically well defined subtype of glioma are the oligodendroglial brain tumors. Approximately 70% of all oligodendrogliomas have a combined loss of the entire 1p and 19q chromosomal arms. This remarkably high frequency suggests that the remaining arms harbor yet to be identified tumor suppressor genes.

Delayed and accelerated aging share common longevity assurance mechanisms.

Mutant dwarf and calorie-restricted mice benefit from healthy aging and unusually long lifespan. In contrast, mouse models for DNA repair-deficient progeroid syndromes age and die prematurely. To identify mechanisms that regulate mammalian longevity, we quantified the parallels between the genome-wide liver expression profiles of mice with those two extremes of lifespan.

Nasopharyngeal co-colonization with Staphylococcus aureus and Streptococcus pneumoniae in children is bacterial genotype independent.

Bacterial interference between Staphylococcus aureus and Streptococcus pneumoniae in the nasopharynx has been observed during colonization, which might have important clinical implications for the widespread use of pneumococcal conjugate vaccine in young children. This study aimed to determine whether the capacity of Staph. aureus to compete with Strep.

HeatMapper: powerful combined visualization of gene expression profile correlations, genotypes, phenotypes and sample characteristics.

Background: Accurate interpretation of data obtained by unsupervised analysis of large scale expression profiling studies is currently frequently performed by visually combining sample-gene heatmaps and sample characteristics. This method is not optimal for comparing individual samples or groups of samples. Here, we describe an approach to visually integrate the results of unsupervised and supervised cluster analysis using a correlation plot and additional sample metadata.

TF Target Mapper: a BLAST search tool for the identification of Transcription Factor target genes.

Background: In the current era of high throughput genomics a major challenge is the genome-wide identification of target genes for specific transcription factors. Chromatin immunoprecipitation (ChIP) allows the isolation of in vivo binding sites of transcription factors and provides a powerful tool for examining gene regulation. Crosslinked chromatin is immunoprecipitated with antibodies against specific transcription factors, thus enriching for sequences bound in vivo by these factors in the immunoprecipitated DNA.

DNA microarray analysis for human congenital heart disease.

Right ventricular hypertrophy and failure are prominent features in cyanotic congenital heart disease, tetralogy of Fallot (TF). Patients with TF require primary cardiac surgery at a very young age. To gain insight into the underlying molecular mechanisms of right ventricular hypertrophy and to identify gene(s) involved in TF, differential gene expression profile was assessed using expression-based microarray technology on right ventricular biopsies from young TF patients who underwent primary correction.

Transcriptome analysis reveals cyclobutane pyrimidine dimers as a major source of UV-induced DNA breaks.

Photolyase transgenic mice have opened new avenues to improve our understanding of the cytotoxic effects of ultraviolet (UV) light on skin by providing a means to selectively remove either cyclobutane pyrimidine dimers (CPDs) or pyrimidine (6-4) pyrimidone photoproducts. Here, we have taken a genomics approach to delineate pathways through which CPDs might contribute to the harmful effects of UV exposure. We show that CPDs, rather than other DNA lesions or damaged macromolecules, comprise the principal mediator of the cellular transcriptional response to UV.

Natural population dynamics and expansion of pathogenic clones of Staphylococcus aureus.

The population structure of Staphylococcus aureus carried by healthy humans was determined using a large strain collection of nonclinical origin (n = 829). High-throughput amplified fragment length polymorphism (AFLP) analysis revealed 3 major and 2 minor genetic clusters of S. aureus, which were corroborated by multilocus sequence typing.

Prognostically useful gene-expression profiles in acute myeloid leukemia.

Background: In patients with acute myeloid leukemia (AML) a combination of methods must be used to classify the disease, make therapeutic decisions, and determine the prognosis. However, this combined approach provides correct therapeutic and prognostic information in only 50 percent of cases.

Methods: We determined the gene-expression profiles in samples of peripheral blood or bone marrow from 285 patients with AML using Affymetrix U133A GeneChips containing approximately 13,000 unique genes or expression-signature tags.