Biomimetic synthetic test system based on hydroxyapatite cement for adhesive strength evaluation of experimental mineral-organic bone adhesive materials.

The development of bone adhesive materials is a research field of high relevance for the advancement of clinical procedures. Despite this, there are currently no material candidates meeting the full range of requirements placed on such a material, such as biocompatibility, sufficient mechanical properties and bond strength under biological conditions, practical applicability in a clinical setting, and no adverse effect on the healing process itself. A serious obstacle to the advancement of the field is a lack in standardized methodology leading to comparable results between experiments and different research groups.

Deletion of the transcription factors Hsf1, Msn2 and Msn4 in yeast uncovers transcriptional reprogramming in response to proteotoxic stress.

The response to proteotoxic stresses such as heat shock allows organisms to maintain protein homeostasis under changing environmental conditions. We asked what happens if an organism can no longer react to cytosolic proteotoxic stress. To test this, we deleted or depleted, either individually or in combination, the stress-responsive transcription factors Msn2, Msn4, and Hsf1 in Saccharomyces cerevisiae.

Volumetric Printing Across Melt Electrowritten Scaffolds Fabricates Multi-Material Living Constructs with Tunable Architecture and Mechanics.

Major challenges in biofabrication revolve around capturing the complex, hierarchical composition of native tissues. However, individual 3D printing techniques have limited capacity to produce composite biomaterials with multi-scale resolution. Volumetric bioprinting recently emerged as a paradigm-shift in biofabrication.

Toward a gold standard for benchmarking gene set enrichment analysis.

Motivation: Although gene set enrichment analysis has become an integral part of high-throughput gene expression data analysis, the assessment of enrichment methods remains rudimentary and ad hoc. In the absence of suitable gold standards, evaluations are commonly restricted to selected datasets and biological reasoning on the relevance of resulting enriched gene sets.

Results: We develop an extensible framework for reproducible benchmarking of enrichment methods based on defined criteria for applicability, gene set prioritization and detection of relevant processes.

The Heat Shock Response in Yeast Maintains Protein Homeostasis by Chaperoning and Replenishing Proteins.

Life is resilient because living systems are able to respond to elevated temperatures with an ancient gene expression program called the heat shock response (HSR). In yeast, the transcription of hundreds of genes is upregulated at stress temperatures. Besides stress protection conferred by chaperones, the function of the majority of the upregulated genes under stress has remained enigmatic.

A transcriptional response of NRRL B-598 to a butanol shock.

Background: One of the main obstacles preventing solventogenic clostridia from achieving higher yields in biofuel production is the toxicity of produced solvents. Unfortunately, regulatory mechanisms responsible for the shock response are poorly described on the transcriptomic level. Although the strain NRRL B-598, a promising butanol producer, has been studied under different conditions in the past, its transcriptional response to a shock caused by butanol in the cultivation medium remains unknown.

MS-EmpiRe Utilizes Peptide-level Noise Distributions for Ultra-sensitive Detection of Differentially Expressed Proteins.

Mass spectrometry based proteomics is the method of choice for quantifying genome-wide differential changes of protein expression in a wide range of biological and biomedical applications. Protein expression changes need to be reliably derived from many measured peptide intensities and their corresponding peptide fold changes. These peptide fold changes vary considerably for a given protein.

YESdb: integrative analysis of environmental stress in yeast.

The stress response in the model organisms Saccharomyces cerevisiae is a well-studied system for which many data sets are available. Already in 2000, it was discovered that yeast cells trigger a similar transcriptional response when different types of stress are applied. However, the exact regulatory mechanisms and differences between the different types of stress are still not understood.

Multi-Reference Spectral Library Yields Almost Complete Coverage of Heterogeneous LC-MS/MS Data Sets.

Spectral libraries play a central role in the analysis of data-independent-acquisition (DIA) proteomics experiments. A main assumption in current spectral library tools is that a single characteristic intensity pattern (CIP) suffices to describe the fragmentation of a peptide in a particular charge state (peptide charge pair). However, we find that this is often not the case.

Comparison of six breast cancer classifiers using qPCR.

Motivation: Several gene expression-based risk scores and subtype classifiers for breast cancer were developed to distinguish high- and low-risk patients. Evaluating the performance of these classifiers helps to decide which classifiers should be used in clinical practice for personal therapeutic recommendations. So far, studies that compared multiple classifiers in large independent patient cohorts mostly used microarray measurements.

miR-103 promotes endothelial maladaptation by targeting lncWDR59.

Blood flow at arterial bifurcations and curvatures is naturally disturbed. Endothelial cells (ECs) fail to adapt to disturbed flow, which transcriptionally direct ECs toward a maladapted phenotype, characterized by chronic regeneration of injured ECs. MicroRNAs (miRNAs) can regulate EC maladaptation through targeting of protein-coding RNAs.

RelExplain-integrating data and networks to explain biological processes.

Motivation: The goal of many genome-wide experiments is to explain the changes between the analyzed conditions. Typically, the analysis is started with a set of differential genes DG and the first step is to identify the set of relevant biological processes BP . Current enrichment methods identify the involved biological process via statistically significant overrepresentation of differential genes in predefined sets, but do not further explain how the differential genes interact with each other or which other genes might be important for the enriched process.

Evaluating Transcription Factor Activity Changes by Scoring Unexplained Target Genes in Expression Data.

Several methods predict activity changes of transcription factors (TFs) from a given regulatory network and measured expression data. But available gene regulatory networks are incomplete and contain many condition-dependent regulations that are not relevant for the specific expression measurement. It is not known which combination of active TFs is needed to cause a change in the expression of a target gene.

Resolving Lipid Mediators Maresin 1 and Resolvin D2 Prevent Atheroprogression in Mice.

Rationale: Atheroprogression is a consequence of nonresolved inflammation, and currently a comprehensive overview of the mechanisms preventing resolution is missing. However, in acute inflammation, resolution is known to be orchestrated by a switch from inflammatory to resolving lipid mediators. Therefore, we hypothesized that lesional lipid mediator imbalance favors atheroprogression.

Regulatory Implications of Non-Trivial Splicing: Isoform 3 of Rab1A Shows Enhanced Basal Activity and Is Not Controlled by Accessory Proteins.

Alternative splicing often affects structured and highly conserved regions of proteins, generating so called non-trivial splicing variants of unknown structure and cellular function. The human small G-protein Rab1A is involved in the regulation of the vesicle transfer from the ER to Golgi. A conserved non-trivial splice variant lacks nearly 40% of the sequence of the native Rab1A, including most of the regulatory interaction sites.

Bioconductor's EnrichmentBrowser: seamless navigation through combined results of set- & network-based enrichment analysis.

Background: Enrichment analysis of gene expression data is essential to find functional groups of genes whose interplay can explain experimental observations. Numerous methods have been published that either ignore (set-based) or incorporate (network-based) known interactions between genes. However, the often subtle benefits and disadvantages of the individual methods are confusing for most biological end users and there is currently no convenient way to combine methods for an enhanced result interpretation.

Alternative Splicing in Next Generation Sequencing Data of Saccharomyces cerevisiae.

mRNA splicing is required in about 4% of protein coding genes in Saccharomyces cerevisiae. The gene structure of those genes is simple, generally comprising two exons and one intron. In order to characterize the impact of alternative splicing on the S.

ContextMap 2: fast and accurate context-based RNA-seq mapping.

Background: Mapping of short sequencing reads is a crucial step in the analysis of RNA sequencing (RNA-seq) data. ContextMap is an RNA-seq mapping algorithm that uses a context-based approach to identify the best alignment for each read and allows parallel mapping against several reference genomes.

Results: In this article, we present ContextMap 2, a new and improved version of ContextMap.

Mining RNA-seq data for infections and contaminations.

RNA sequencing (RNA-seq) provides novel opportunities for transcriptomic studies at nucleotide resolution, including transcriptomics of viruses or microbes infecting a cell. However, standard approaches for mapping the resulting sequencing reads generally ignore alternative sources of expression other than the host cell and are little equipped to address the problems arising from redundancies and gaps among sequenced microbe and virus genomes. We show that screening of sequencing reads for contaminations and infections can be performed easily using ContextMap, our recently developed mapping software.

A comprehensive gene regulatory network for the diauxic shift in Saccharomyces cerevisiae.

Existing machine-readable resources for large-scale gene regulatory networks usually do not provide context information characterizing the activating conditions for a regulation and how targeted genes are affected. Although this information is essentially required for data interpretation, available networks are often restricted to not condition-dependent, non-quantitative, plain binary interactions as derived from high-throughput screens. In this article, we present a comprehensive Petri net based regulatory network that controls the diauxic shift in Saccharomyces cerevisiae.

A context-based approach to identify the most likely mapping for RNA-seq experiments.

Background: Sequencing of mRNA (RNA-seq) by next generation sequencing technologies is widely used for analyzing the transcriptomic state of a cell. Here, one of the main challenges is the mapping of a sequenced read to its transcriptomic origin. As a simple alignment to the genome will fail to identify reads crossing splice junctions and a transcriptome alignment will miss novel splice sites, several approaches have been developed for this purpose.

From sets to graphs: towards a realistic enrichment analysis of transcriptomic systems.

Motivation: Current gene set enrichment approaches do not take interactions and associations between set members into account. Mutual activation and inhibition causing positive and negative correlation among set members are thus neglected. As a consequence, inconsistent regulations and contextless expression changes are reported and, thus, the biological interpretation of the result is impeded.

Vorescore--fold recognition improved by rescoring of protein structure models.

Summary: The identification of good protein structure models and their appropriate ranking is a crucial problem in structure prediction and fold recognition. For many alignment methods, rescoring of alignment-induced models using structural information can improve the separation of useful and less useful models as compared with the alignment score. Vorescore, a template-based protein structure model rescoring system is introduced.

miRSel: automated extraction of associations between microRNAs and genes from the biomedical literature.

Background: MicroRNAs have been discovered as important regulators of gene expression. To identify the target genes of microRNAs, several databases and prediction algorithms have been developed. Only few experimentally confirmed microRNA targets are available in databases.