FastqPuri: high-performance preprocessing of RNA-seq data.

Background: RNA sequencing (RNA-seq) has become the standard means of analyzing gene and transcript expression in high-throughput. While previously sequence alignment was a time demanding step, fast alignment methods and even more so transcript counting methods which avoid mapping and quantify gene and transcript expression by evaluating whether a read is compatible with a transcript, have led to significant speed-ups in data analysis. Now, the most time demanding step in the analysis of RNA-seq data is preprocessing the raw sequence data, such as running quality control and adapter, contamination and quality filtering before transcript or gene quantification.

High-Dimensional Profiling for Computational Diagnosis.

New technologies allow for high-dimensional profiling of patients. For instance, genome-wide gene expression analysis in tumors or in blood is feasible with microarrays, if all transcripts are known, or even without this restriction using high-throughput RNA sequencing. Other technologies like NMR finger printing allow for high-dimensional profiling of metabolites in blood or urine.

EasyStrata: evaluation and visualization of stratified genome-wide association meta-analysis data.

Unlabelled: The R package EasyStrata facilitates the evaluation and visualization of stratified genome-wide association meta-analyses (GWAMAs) results. It provides (i) statistical methods to test and account for between-strata difference as a means to tackle gene-strata interaction effects and (ii) extended graphical features tailored for stratified GWAMA results. The software provides further features also suitable for general GWAMAs including functions to annotate, exclude or highlight specific loci in plots or to extract independent subsets of loci from genome-wide datasets.

Lactate-modulated induction of THBS-1 activates transforming growth factor (TGF)-beta2 and migration of glioma cells in vitro.

Background: An important phenomenon observed in glioma metabolism is increased aerobic glycolysis in tumor cells, which is generally referred to as the Warburg effect. Transforming growth factor (TGF)-beta2, which we previously showed to be induced by lactic acid, is a key pathophysiological factor in glioblastoma, leading to increased invasion and severe local immunosuppression after proteolytic cleavage from its latency associated peptide. In this study we tested the hypothesis, that lactate regulates TGF-beta2 expression and glioma cell migration via induction of Thrombospondin-1 (THBS-1), a TGF-beta activating protein.

LMX1B is essential for the maintenance of differentiated podocytes in adult kidneys.

Mutations of the LMX1B gene cause nail-patella syndrome, a rare autosomal-dominant disorder affecting the development of the limbs, eyes, brain, and kidneys. The characterization of conventional Lmx1b knockout mice has shown that LMX1B regulates the development of podocyte foot processes and slit diaphragms, but studies using podocyte-specific Lmx1b knockout mice have yielded conflicting results regarding the importance of LMX1B for maintaining podocyte structures. In order to address this question, we generated inducible podocyte-specific Lmx1b knockout mice.

Commonly altered genomic regions in acute myeloid leukemia are enriched for somatic mutations involved in chromatin remodeling and splicing.

Acute myeloid leukemia (AML) is characterized by molecular heterogeneity. As commonly altered genomic regions point to candidate genes involved in leukemogenesis, we used microarray-based comparative genomic hybridization and single nucleotide polymorphism profiling data of 391 AML cases to further narrow down genomic regions of interest. Targeted resequencing of 1000 genes located in the critical regions was performed in a representative cohort of 50 AML samples comprising all major cytogenetic subgroups.

T cells become licensed in the lung to enter the central nervous system.

The blood–brain barrier (BBB) and the environment of the central nervous system (CNS) guard the nervous tissue from peripheral immune cells. In the autoimmune disease multiple sclerosis, myelin-reactive T-cell blasts are thought to transgress the BBB and create a pro-inflammatory environment in the CNS, thereby making possible a second autoimmune attack that starts from the leptomeningeal vessels and progresses into the parenchyma. Using a Lewis rat model of experimental autoimmune encephalomyelitis, we show here that contrary to the expectations of this concept, T-cell blasts do not efficiently enter the CNS and are not required to prepare the BBB for immune-cell recruitment.

Transcriptional profiles of CD133+ and CD133- glioblastoma-derived cancer stem cell lines suggest different cells of origin.

Glioblastoma multiforme (GBM) is paradigmatic for the investigation of cancer stem cells (CSC) in solid tumors. Growing evidence suggests that different types of CSC lead to the formation of GBM. This has prompted the present comparison of gene expression profiles between 17 GBM CSC lines and their different putative founder cells.

ReseqChip: automated integration of multiple local context probe data from the MitoChip array in mitochondrial DNA sequence assembly.

Background: The Affymetrix MitoChip v2.0 is an oligonucleotide tiling array for the resequencing of the human mitochondrial (mt) genome. For each of 16,569 nucleotide positions of the mt genome it holds two sets of four 25-mer probes each that match the heavy and the light strand of a reference mt genome and vary only at their central position to interrogate all four possible alleles.

Comparison of gene expression profiles between human and mouse monocyte subsets.

Blood of both humans and mice contains 2 main monocyte subsets. Here, we investigated the extent of their similarity using a microarray approach. Approximately 270 genes in humans and 550 genes in mice were differentially expressed between subsets by 2-fold or more.

Integrative normalization and comparative analysis for metabolic fingerprinting by comprehensive two-dimensional gas chromatography-time-of-flight mass spectrometry.

Comprehensive two-dimensional gas chromatography-time-of-flight mass spectrometry (GC x GC-TOF-MS) was applied to the comparative metabolic fingerprinting of a wild-type versus a double mutant strain of Escherichia coli lacking the transhydrogenases UdhA and PntAB. Using peak lists generated with the Leco ChromaTOF software as input, we developed retention time correction and data alignment tools (INCA). The accuracy of peak alignment and detection of 1.

Computational diagnostics with gene expression profiles.

Gene expression profiling using micro-arrays is a modern approach for molecular diagnostics. In clinical micro-array studies, researchers aim to predict disease type, survival, or treatment response using gene expression profiles. In this process, they encounter a series of obstacles and pitfalls.

Substantial biases in ultra-short read data sets from high-throughput DNA sequencing.

Novel sequencing technologies permit the rapid production of large sequence data sets. These technologies are likely to revolutionize genetics and biomedical research, but a thorough characterization of the ultra-short read output is necessary. We generated and analyzed two Illumina 1G ultra-short read data sets, i.

SHARCGS, a fast and highly accurate short-read assembly algorithm for de novo genomic sequencing.

The latest revolution in the DNA sequencing field has been brought about by the development of automated sequencers that are capable of generating giga base pair data sets quickly and at low cost. Applications of such technologies seem to be limited to resequencing and transcript discovery, due to the shortness of the generated reads. In order to extend the fields of application to de novo sequencing, we developed the SHARCGS algorithm to assemble short-read (25-40-mer) data with high accuracy and speed.

Neutrality, compensation, and negative selection during evolution of B-cell development transcriptomes.

B cells develop in the mammalian bone marrow through a sequence of precursor stages, which can be ordered by the recombination status of their immunoglobulin loci. This developmental pathway is functionally similar between mice and man. However, whether this similarity is based on usage of the same genes is unknown.

Annotation-based distance measures for patient subgroup discovery in clinical microarray studies.

Motivation: Clustering algorithms are widely used in the analysis of microarray data. In clinical studies, they are often applied to find groups of co-regulated genes. Clustering, however, can also stratify patients by similarity of their gene expression profiles, thereby defining novel disease entities based on molecular characteristics.

Gene-expression profiling identifies distinct subclasses of core binding factor acute myeloid leukemia.

Core binding factor (CBF) leukemias, characterized by either inv(16)/t(16;16) or t(8;21), constitute acute myeloid leukemia (AML) subgroups with favorable prognosis. However, there exists substantial biologic and clinical heterogeneity within these cytogenetic groups that is not fully reflected by the current classification system. To improve the molecular characterization we profiled gene expression in a large series (n = 93) of AML patients with CBF leukemia [(inv (16), n = 55; t(8;21), n = 38)].

Expression of late cell cycle genes and an increased proliferative capacity characterize very early relapse of childhood acute lymphoblastic leukemia.

Purpose: In childhood acute lymphoblastic leukemia (ALL), approximately 25% of patients suffer from relapse. In recurrent disease, despite intensified therapy, overall cure rates of 40% remain unsatisfactory and survival rates are particularly poor in certain subgroups. The probability of long-term survival after relapse is predicted from well-established prognostic factors (i.

OrderedList--a bioconductor package for detecting similarity in ordered gene lists.

Unlabelled: OrderedList is a Bioconductor compliant package for meta-analysis based on ordered gene lists like those resulting from differential gene expression analysis. Our package quantifies the similarity between gene lists. The significance of the similarity score is estimated from random scores computed on perturbed data.

stam--a Bioconductor compliant R package for structured analysis of microarray data.

Background: Genome wide microarray studies have the potential to unveil novel disease entities. Clinically homogeneous groups of patients can have diverse gene expression profiles. The definition of novel subclasses based on gene expression is a difficult problem not addressed systematically by currently available software tools.

Molecular decomposition of complex clinical phenotypes using biologically structured analysis of microarray data.

Motivation: Today, the characterization of clinical phenotypes by gene-expression patterns is widely used in clinical research. If the investigated phenotype is complex from the molecular point of view, new challenges arise and these have not been addressed systematically. For instance, the same clinical phenotype can be caused by various molecular disorders, such that one observes different characteristic expression patterns in different patients.