PEDL+: protein-centered relation extraction from PubMed at your fingertip.

Summary: Relation extraction (RE) from large text collections is an important tool for database curation, pathway reconstruction, or functional omics data analysis. In practice, RE often is part of a complex data analysis pipeline requiring specific adaptations like restricting the types of relations or the set of proteins to be considered. However, current systems are either non-programmable web sites or research code with fixed functionality.

A computational model of the DNA damage-induced IKK/ NF-κB pathway reveals a critical dependence on irradiation dose and PARP-1.

The activation of IKK/NF-κB by genotoxic stress is a crucial process in the DNA damage response. Due to the anti-apoptotic impact of NF-κB, it can affect cell-fate decisions upon DNA damage and therefore interfere with tumor therapy-induced cell death. Here, we developed a dynamical model describing IKK/NF-κB signaling that faithfully reproduces quantitative time course data and enables a detailed analysis of pathway regulation.

Resolving Crosstalk Between Signaling Pathways Using Mathematical Modeling and Time-Resolved Single Cell Data.

Crosstalk between signaling pathways can modulate the cellular response to stimuli and is therefore an important part of signal transduction. For a comprehensive understanding of cellular responses, identifying points of interaction between the underlying molecular networks is essential. Here, we present an approach that allows the systematic prediction of such interactions by perturbing one pathway and quantifying the concomitant alterations in the response of a second pathway.

Patient-Specific Modeling of Diffuse Large B-Cell Lymphoma.

Personalized medicine aims to tailor treatment to patients based on their individual genetic or molecular background. Especially in diseases with a large molecular heterogeneity, such as diffuse large B-cell lymphoma (DLBCL), personalized medicine has the potential to improve outcome and/or to reduce resistance towards treatment. However, integration of patient-specific information into a computational model is challenging and has not been achieved for DLBCL.

Quantitative lineage analysis identifies a hepato-pancreato-biliary progenitor niche.

Studies based on single cells have revealed vast cellular heterogeneity in stem cell and progenitor compartments, suggesting continuous differentiation trajectories with intermixing of cells at various states of lineage commitment and notable degrees of plasticity during organogenesis. The hepato-pancreato-biliary organ system relies on a small endoderm progenitor compartment that gives rise to a variety of different adult tissues, including the liver, pancreas, gall bladder and extra-hepatic bile ducts. Experimental manipulation of various developmental signals in the mouse embryo has underscored important cellular plasticity in this embryonic territory.

A systematic approach to decipher crosstalk in the p53 signaling pathway using single cell dynamics.

The transcription factors NF-κB and p53 are key regulators in the genotoxic stress response and are critical for tumor development. Although there is ample evidence for interactions between both networks, a comprehensive understanding of the crosstalk is lacking. Here, we developed a systematic approach to identify potential interactions between the pathways.

Identification of new IκBα complexes by an iterative experimental and mathematical modeling approach.

The transcription factor nuclear factor kappa-B (NFκB) is a key regulator of pro-inflammatory and pro-proliferative processes. Accordingly, uncontrolled NFκB activity may contribute to the development of severe diseases when the regulatory system is impaired. Since NFκB can be triggered by a huge variety of inflammatory, pro-and anti-apoptotic stimuli, its activation underlies a complex and tightly regulated signaling network that also includes multi-layered negative feedback mechanisms.

Analysing the role of UVB-induced translational inhibition and PP2Ac deactivation in NF-κB signalling using a minimal mathematical model.

Activation of nuclear factor κB (NF-κB) by interleukin-1β (IL-1) usually results in an anti-apoptotic activity that is rapidly terminated by a negative feedback loop involving NF-κB dependent resynthesis of its own inhibitor IκBα. However, apoptosis induced by ultraviolet B radiation (UVB) is not attenuated, but significantly enhanced by co-stimulation with IL-1 in human epithelial cells. Under these conditions NF-κB remains constitutively active and turns into a pro-apoptotic factor by selectively repressing anti-apoptotic genes.