Prediction of polyspecificity from antibody sequence data by machine learning.

Antibodies are generated with great diversity in nature resulting in a set of molecules, each optimized to bind a specific target. Taking advantage of their diversity and specificity, antibodies make up for a large part of recently developed biologic drugs. For therapeutic use antibodies need to fulfill several criteria to be safe and efficient.

ZBIT Bioinformatics Toolbox: A Web-Platform for Systems Biology and Expression Data Analysis.

Bioinformatics analysis has become an integral part of research in biology. However, installation and use of scientific software can be difficult and often requires technical expert knowledge. Reasons are dependencies on certain operating systems or required third-party libraries, missing graphical user interfaces and documentation, or nonstandard input and output formats.

JSBML 1.0: providing a smorgasbord of options to encode systems biology models.

Unlabelled: JSBML, the official pure Java programming library for the Systems Biology Markup Language (SBML) format, has evolved with the advent of different modeling formalisms in systems biology and their ability to be exchanged and represented via extensions of SBML. JSBML has matured into a major, active open-source project with contributions from a growing, international team of developers who not only maintain compatibility with SBML, but also drive steady improvements to the Java interface and promote ease-of-use with end users.

Availability And Implementation: Source code, binaries and documentation for JSBML can be freely obtained under the terms of the LGPL 2.

Evaluation of toxicogenomics approaches for assessing the risk of nongenotoxic carcinogenicity in rat liver.

The current gold-standard method for cancer safety assessment of drugs is a rodent two-year bioassay, which is associated with significant costs and requires testing a high number of animals over lifetime. Due to the absence of a comprehensive set of short-term assays predicting carcinogenicity, new approaches are currently being evaluated. One promising approach is toxicogenomics, which by virtue of genome-wide molecular profiling after compound treatment can lead to an increased mechanistic understanding, and potentially allow for the prediction of a carcinogenic potential via mathematical modeling.

Integrated enrichment analysis and pathway-centered visualization of metabolomics, proteomics, transcriptomics, and genomics data by using the InCroMAP software.

In systems biology, the combination of multiple types of omics data, such as metabolomics, proteomics, transcriptomics, and genomics, yields more information on a biological process than the analysis of a single type of data. Thus, data from different omics platforms is usually combined in one experimental setup to obtain insight into a biological process or a disease state. Particularly high accuracy metabolomics data from modern mass spectrometry instruments is currently more and more integrated into biological studies.

Ha-ras and β-catenin oncoproteins orchestrate metabolic programs in mouse liver tumors.

The process of hepatocarcinogenesis in the diethylnitrosamine (DEN) initiation/phenobarbital (PB) promotion mouse model involves the selective clonal outgrowth of cells harboring oncogene mutations in Ctnnb1, while spontaneous or DEN-only-induced tumors are often Ha-ras- or B-raf-mutated. The molecular mechanisms and pathways underlying these different tumor sub-types are not well characterized. Their identification may help identify markers for xenobiotic promoted versus spontaneously occurring liver tumors.

TFpredict and SABINE: sequence-based prediction of structural and functional characteristics of transcription factors.

One of the key mechanisms of transcriptional control are the specific connections between transcription factors (TF) and cis-regulatory elements in gene promoters. The elucidation of these specific protein-DNA interactions is crucial to gain insights into the complex regulatory mechanisms and networks underlying the adaptation of organisms to dynamically changing environmental conditions. As experimental techniques for determining TF binding sites are expensive and mostly performed for selected TFs only, accurate computational approaches are needed to analyze transcriptional regulation in eukaryotes on a genome-wide level.

Integrative pathway-based approach for genome-wide association studies: identification of new pathways for rheumatoid arthritis and type 1 diabetes.

Genome-wide association studies (GWAS) led to the identification of numerous novel loci for a number of complex diseases. Pathway-based approaches using genotypic data provide tangible leads which cannot be identified by single marker approaches as implemented in GWAS. The available pathway analysis approaches mainly differ in the employed databases and in the applied statistics for determining the significance of the associated disease markers.

Parkinson's disease: dopaminergic nerve cell model is consistent with experimental finding of increased extracellular transport of α-synuclein.

Background: Parkinson's disease is an age-related disease whose pathogenesis is not completely known. Animal models exist for investigating the disease but not all results can be easily transferred to humans. Therefore, mathematical or probabilistic models for the human disease are to be constructed in silico in order to predict specific processes within a cell, such as the dopamine metabolism and transport processes in a neuron.

Path2Models: large-scale generation of computational models from biochemical pathway maps.

Background: Systems biology projects and omics technologies have led to a growing number of biochemical pathway models and reconstructions. However, the majority of these models are still created de novo, based on literature mining and the manual processing of pathway data.

Results: To increase the efficiency of model creation, the Path2Models project has automatically generated mathematical models from pathway representations using a suite of freely available software.

A toxicogenomic approach for the prediction of murine hepatocarcinogenesis using ensemble feature selection.

The current strategy for identifying the carcinogenicity of drugs involves the 2-year bioassay in male and female rats and mice. As this assay is cost-intensive and time-consuming there is a high interest in developing approaches for the screening and prioritization of drug candidates in preclinical safety evaluations. Predictive models based on toxicogenomics investigations after short-term exposure have shown their potential for assessing the carcinogenic risk.

Precise generation of systems biology models from KEGG pathways.

Background: The KEGG PATHWAY database provides a plethora of pathways for a diversity of organisms. All pathway components are directly linked to other KEGG databases, such as KEGG COMPOUND or KEGG REACTION. Therefore, the pathways can be extended with an enormous amount of information and provide a foundation for initial structural modeling approaches.

InCroMAP: integrated analysis of cross-platform microarray and pathway data.

Summary: Microarrays are commonly used to detect changes in gene expression between different biological samples. For this purpose, many analysis tools have been developed that offer visualization, statistical analysis and more sophisticated analysis methods. Most of these tools are designed specifically for messenger RNA microarrays.

Identification of Dlk1-Dio3 imprinted gene cluster noncoding RNAs as novel candidate biomarkers for liver tumor promotion.

The molecular events during nongenotoxic carcinogenesis and their temporal order are poorly understood but thought to include long-lasting perturbations of gene expression. Here, we have investigated the temporal sequence of molecular and pathological perturbations at early stages of phenobarbital (PB) mediated liver tumor promotion in vivo. Molecular profiling (mRNA, microRNA [miRNA], DNA methylation, and proteins) of mouse liver during 13 weeks of PB treatment revealed progressive increases in hepatic expression of long noncoding RNAs and miRNAs originating from the Dlk1-Dio3 imprinted gene cluster, a locus that has recently been associated with stem cell pluripotency in mice and various neoplasms in humans.

Pathway-based visualization of cross-platform microarray datasets.

Motivation: Traditionally, microarrays were almost exclusively used for the genome-wide analysis of differential gene expression. But nowadays, their scope of application has been extended to various genomic features, such as microRNAs (miRNAs), proteins and DNA methylation (DNAm). Most available methods for the visualization of these datasets are focused on individual platforms and are not capable of integratively visualizing multiple microarray datasets from cross-platform studies.

Qualitative translation of relations from BioPAX to SBML qual.

Motivation: The biological pathway exchange language (BioPAX) and the systems biology markup language (SBML) belong to the most popular modeling and data exchange languages in systems biology. The focus of SBML is quantitative modeling and dynamic simulation of models, whereas the BioPAX specification concentrates mainly on visualization and qualitative analysis of pathway maps. BioPAX describes reactions and relations.

Linking the epigenome to the genome: correlation of different features to DNA methylation of CpG islands.

DNA methylation of CpG islands plays a crucial role in the regulation of gene expression. More than half of all human promoters contain CpG islands with a tissue-specific methylation pattern in differentiated cells. Still today, the whole process of how DNA methyltransferases determine which region should be methylated is not completely revealed.

Inferring statin-induced gene regulatory relationships in primary human hepatocytes.

Motivation: Statins are the most widely used cholesterol-lowering drugs. The primary target of statins is HMG-CoA reductase, a key enzyme in cholesterol synthesis. However, statins elicit pleitropic responses including beneficial as well as adverse effects in the liver or other organs.

KEGGtranslator: visualizing and converting the KEGG PATHWAY database to various formats.

Summary: The KEGG PATHWAY database provides a widely used service for metabolic and nonmetabolic pathways. It contains manually drawn pathway maps with information about the genes, reactions and relations contained therein. To store these pathways, KEGG uses KGML, a proprietary XML-format.

JSBML: a flexible Java library for working with SBML.

Summary: The specifications of the Systems Biology Markup Language (SBML) define standards for storing and exchanging computer models of biological processes in text files. In order to perform model simulations, graphical visualizations and other software manipulations, an in-memory representation of SBML is required. We developed JSBML for this purpose.

ModuleMaster: a new tool to decipher transcriptional regulatory networks.

Unlabelled: In this article we present ModuleMaster, a novel application for finding cis-regulatory modules (CRMs) in sets of co-expressed genes. The application comes with a newly developed method which not only considers transcription factor binding information but also multivariate functional relationships between regulators and target genes to improve the detection of CRMs. Given only the results of a microarray and a subsequent clustering experiment, the program includes all necessary data and algorithms to perform every step to find CRMs.